Skip to main content
Erschienen in: BMC Cardiovascular Disorders 1/2020

Open Access 01.12.2020 | Research article

The effect of milrinone on mortality in adult patients who underwent CABG surgery: a systematic review of randomized clinical trials with a meta-analysis and trial sequential analysis

verfasst von: Yu-shan Ren, Lan-fang Li, Tao Peng, Yu-jun Tan, Ying Sun, Guo-liang Cheng, Gui-min Zhang, Jie Li

Erschienen in: BMC Cardiovascular Disorders | Ausgabe 1/2020

Abstract

Background

As an inodilator, milrinone is commonly used for patients who undergo coronary artery bypass graft (CABG) surgery because of its effectiveness in decreasing the cardiac index and mitral regurgitation. The aim of this study was to perform a systematic review and meta-analysis of existing studies from the past 20 years to evaluate the impact of milrinone on mortality in patients who undergo CABG surgery.

Methods

We performed a systematic literature search on the application of milrinone in patients who underwent CABG surgery in studies published between 1997 and 2017 in BioMed Central, PubMed, EMBASE, and the Cochrane Central Register. The included studies evaluated milrinone groups compared to groups receiving either placebo or standard treatment and further compared the systemic administration.

Results

The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significant difference in mortality between the milrinone group and the placebo/standard care group when patients underwent CABG surgery. In addition, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmia was lower in the milrinone group than in the placebo/standard care group. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction, myocardial ischemia, and arrhythmia was significantly different. However, the occurrence of stroke and renal failure, the duration of inotropic support (h), the need for an intra-aortic balloon pump (IABP), and mechanical ventilation (h) between these two groups showed no differences.

Conclusions

Based on the current results, compared with placebo, milrinone might be unable to decrease mortality in adult CABG surgical patients but can significantly ameliorate the occurrence of MI, myocardial ischemia, and arrhythmia. These results provide evidence for the further clinical application of milrinone and of therapeutic strategies for CABG surgery. However, along with milrinone application in clinical use, sufficient data from randomized clinical trials need to be collected, and the potential benefits and adverse effects should be analyzed and reevaluated.
Hinweise

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
AKI
Acute kidney injury
ARF
Acute renal failure
CABG
Coronary artery bypass graft
CAD
Coronary artery disease
cAMP
Cyclic adenosine phosphate
CVDs
Cardiovascular diseases
LOS
Low output syndrome
MI
Myocardial infarction
WHO
World Health Organization
PDE
Phosphodiesterase
RCTs
Randomized controlled trials
PRISMA
Preferred reporting items for systematic reviews and meta-analyses
LVEF
Left ventricular ejection fraction
AKI
Acute kidney injury
IABP
Intra-aortic balloon pump

Background

In 2017, the World Health Organization (WHO) reported that nearly 17.7 million people die of cardiovascular diseases (CVDs) every year, accounting for 31% of all global deaths. Coronary artery disease (CAD) refers to the class of diseases of vascular stenosis or obstruction caused by coronary artery atherosclerotic lesions, resulting in myocardial ischemia, hypoxia or necrosis and including stable and unstable angina, myocardial infarction (MI), and sudden cardiac death [1]. Furthermore, CAD can cause serious complications due to multiple risk factors, such as a heart attack, damaged heart muscle, and an irregular heartbeat, and can result in sudden death [24] . At present, coronary artery bypass grafting (CABG) surgery is the primary strategy for CAD treatment [59]. CABG surgery is a surgical procedure in which vascular access between the root of the ascending aorta and the distal end of the lesion site is established to make blood bypass the coronary artery lesion site, flow to the distal end of the coronary artery stenosis or obstruction, and reach the ischemic myocardium, thus improving coronary perfusion and increasing myocardial oxygen supply [1012]. Although CABG surgery has been reported to be associated with low costs, superior outcomes, and particularly short-term mortality [1316], multiple complications, such as MI, myocardial ischemia, arrhythmia, stroke, and acute renal failure (ARF), are impossible to ignore and are still concerning to researchers and clinical doctors [7, 1720], To minimize the occurrence of postoperative complications, pre- and/or postoperative medicinal applications, such as phosphodiesterase (PDE) III inhibitors, have been the primary strategies to date [2123].
By reducing the inactivation of cyclic adenosine phosphate (cAMP) in cardiomyocytes, PDE III inhibitors enhance myocardial contractility and produce positive inotropic effects [24, 25]; a higher concentration of cAMP results in contractility, increasing myocardial tissue and the vasodilatory effect on vascular smooth muscle [26, 27]. Milrinone, a PDE III inhibitor, is primarily used after open-heart surgery because it can avoid cardiopulmonary bypass [28], enhance cardiac contractility [29], prevent vasospasm [30], and ameliorate low output syndrome (LOS) [31]. However, recent studies have demonstrated that the efficacy and safety profile of milrinone remains controversial, although it has been implemented in several guidelines [32, 33]. In some studies on cardiac surgeries, a tendency for an increased mortality rate and incidence of arrhythmia has been found in milrinone groups compared with control groups [34, 35]. However, another study evaluating milrinone for acute heart failure treatment revealed that milrinone might be safe and effective [36]. All contradictory outcomes resulted from the limited number of included patients [34] and the lack of key methodological criteria [37] not based on previously published protocols [35]. No studies have assessed the incidence of postoperative complications.
To avoid bias results from any unclear risk of bias that were included, our objective was to conduct a systematic review and meta-analysis of existing randomized controlled trials (RCTs) and to assess mortality between milrinone-treated patients and patients receiving placebo/standard care. The incidence of postoperative complications, such as MI, myocardial ischemia, arrhythmia, stroke, and acute kidney injury (AKI), was estimated simultaneously.

Methods

Search strategy

The search strategy aimed to include any RCTs conducted among adult patients who underwent CABG surgery and were treated with milrinone and in which these patients were compared to those treated only with placebo/standard care. A pertinent study search was independently conducted in BioMed Central, PubMed, Embase, and the Cochrane Central Register (all searches updated in November 2017) by 3 trained investigators [Lan-fang Li, Guo-liang Cheng, and Ying Sun]. We searched database for randomised trials through coronary artery bypass grafting (CABG) in the treatment of left main coronary artery disease with pre- and/or postoperative milrinone applications using the search terms “coronary artery bypass operation”, “coronary artery bypass grafting”, “randomised”, “randomized”, postoperative milrinone, or preoperative milrinone. No language restrictions were imposed, and non-English-language articles were translated before analysis.

Study selection

References retrieved using the literature searches and databases were screened. When potentially pertinent studies were found, complete articles were retrieved. The inclusion criteria were as follows: patients randomly allocated according to treatment, groups receiving milrinone compared with groups receiving placebo/standard care with no restrictions in terms of dose or time of administration, CABG surgery performed in adult patients, and information provided on primary outcomes (endpoint). The exclusion criteria were as follows: lack of outcome (mortality) data, duplicate publications, animal experimental studies, articles published as abstracts only, and pediatric populations. Three investigators independently assessed compliance with the selection criteria and selected studies for the final analysis; divergences were resolved by consensus, and if issues persisted, the reference was evaluated by 4 investigators independently.

Data extraction and study characteristics

The following details were independently extracted from the retrieved studies by 4 trained investigators: number of patients, surgical type, clinical setting, milrinone dosage, treatment duration, follow-up, mortality, and operative complications (such as MI, myocardial ischemia, arrhythmia, stroke, and AKI). The primary endpoint of the current analysis was mortality. Additionally, MI (per author definition), acute renal failure (per author definition), myocardial ischemia, arrhythmia, stroke, AKI, mechanical ventilation, lengths of intensive care unit and hospital stay were the secondary endpoints.

Quality assessment

The included trials were assessed according to the Cochrane Collaboration methods to evaluate the risk of bias and the internal validity by 3 independent reviewers.

Data analysis and synthesis

RevMan (Review Manager, version 5.2, Nordic Cochrane Center, Cochrane Collaboration, Copenhagen, 2012) and Stata (Stata Statistical Software: release 13, StataCorp LP, College Station, Texas) were utilized to analyze data extracted from the selected articles. A Q-test was applied to measure the statistical heterogeneity, and I2 was used as a quantitative measure of the degree of heterogeneity. The date of mortality was estimated to compute the individual and pooled relative risk (RR) with a 95% confidence interval (CI) by means of the Mantel-Haenszel method. The presence of heterogeneity across trials was also evaluated, with I2 < 25% indicating no significant heterogeneity when the fixed-effects model was used. In contrast, in the case of moderate or substantial heterogeneity (I2 > 25%), a random-effects model was used. Funnel plots were used to explore the small-study risk of bias by analytic appraisal based on Peters’ regression asymmetry test. Meta-regression analyses were performed to investigate sample size, mean number of grafts, mean number of arterial grafts, mean pump time, mean AoXclamp time, mean preop left ventricular ejection fraction (LVEF), pre-op drugs, post-op inotropes, pre-op shock/MI, and post-op intra-aortic balloon pump (IABP) as potential causes for heterogeneity.
The Cochrane Collaboration principals and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines complied with the standards for the current study. Two-tailed levels of 0.05 and 0.1 were set as the limit for the statistical significance of the hypothesis and heterogeneity analyses, respectively. The p values were not revised throughout the assessment.

Results

A total of 1463 articles were identified and screened. After the exclusion of 1301 articles due to irrelevant titles or abstracts, 162 full-text studies were eligible and assessed according to the selection criteria (Fig. 1). Of these, the most common reasons for exclusion were as follows: valid data could not be obtained by the authors (87 studies), milrinone was compared with other drugs (17 studies), pediatric populations were used (11 studies), studies were nonrandomized controlled trials (9 studies), crossover studies (5 studies), studies published as abstracts only (4 studies), studies used mechanical devices as controls (4 studies), studies used inhaled milrinone (3 studies), studies used randomization of brain-dead organ donors (3 studies), studies were animal studies (2 studies), and studies used healthy volunteers (1 study). Ultimately, sixteen randomized clinical trials were assessed in compliance with the inclusion criteria (Table 1) [31, 3847, 5255].
Table 1
A Description of the Studies Included in the Meta-Analysis
First Author
Journal
Year
Procedures
Control
Inclusion Criteria
Exclusion Criteria
Primary Outcome
Secondary Outcome
Arbeus M [38]
Journal of Cardiothoracic and Vascular Anesthesia
2009
Elective CABG
Placebo
Stable angina,
LVEF (%) > 30%,
Sinus rhythm.
Unspecified
Graft flow
Unspecified
Couture P [39]
Canadian Journal of Anaesthesia
2007
Elective CABG
Placebo
Ischemic heart disease, LV diastolic dysfunction.
Mitral and aortic valvular disease,
Atrial fibrillation or pacemaker, Contraindication to TEE.
LV diastolic dysfunction
Unspecified
Doolan LA [40]
Journal of Cardiothoracic and Vascular Anesthesia
1997
Elective CABG and valvular surgery
Placebo
LVEF (%) ≤ 35%,
Mean PAP ≥ 20 mmHg.
Supraventricular tachyarrhythmias,
Platelet countless than 100 × 109/L (preoperative),
Significant primary hepatic or renal disease.
Success or failure in weaning from bypass.
Hemodynamic variables
Guo YJ [9]
Chinese Heart Journal
2014
Elective CABG
Placebo
CABG surgery,
LVEF (%) < 35%,
Emergency surgery,
Myocardial infarction,
Ventricular arrhythmias,
Requiring inotropic support.
Myocardial ischemia and/or MI incidence
Mean arterial pressure, Requirements for vasopressors, Death, Length of hospital stay, Serum potassium and creatinine Concentrations.
Hadadzadeh M [41]
Acta medica Iranica
2013
Elective CABG (off-pump)
Placebo
Severe myocardium dysfunction (LVEF (%) < 35%)
Emergency CABG,
Myocardial infarction,
Ventricular arrhythmias,
Requiring inotropic support.
Myocardial ischemia and/or MI incidence
Unspecified
Hamada Y [42]
Japanese circulation journal
1999
Elective CABG and valvular surgery
Standard treatment
Unspecified
Unspecified
Hemodynamic variables
Unspecified
Hayashida N [43]
Annals of Thoracic Surgery
1999
Elective CABG
Standard treatment
Isolated CABG surgery
Myocardial ischemia,
Acute myocardial infarction
Cytokine production
Unspecified
Jebeli M [44]
Cardiology Journal
2010
Elective CABG
Placebo
LVEF (%) < 35%,
Emergency CABG,
Myocardial infarction,
Ventricular arrhythmias,
Requiring inotropic support.
Myocardial ischemia and/or MI incidence
Cardiac enzyme levels,
Duration of inotropic support.
Jo HR [45]
Korean Journal of Anesthesiology
2010
Elective CABG (off-pump)
Placebo
CABG surgery, Normal LV function.
LVEF or RVEF (%) < 40%,
Valvular heart disease,
Severe cerebral or renal dysfunction, Emergency surgery.
Right ventricular function and early outcomes
Unspecified
Kwak YL [46]
European journal of cardio-thoracic surgery
2004
Elective CABG (off-pump)
Placebo
Unspecified
Renal or hepatic dysfunction, Thrombocytopenia,
Coagulopathy.
Cardiac Index
Unspecified
Lee JH [32]
Journal of korean medical science
2006
Elective CABG (off-pump)
Placebo
RVEF (%) < 35%
Hepatic or renal dysfunction, Thrombocytopenia or coagulopathy,
Supraventricular tachyarrhythmias,
Single coronary artery disease,
History of receiving inotropic agents.
Right ventricular function and early outcomes
Unspecified
Möllhoff T [47]
Anesthesiology
1999
Elective CABG
Placebo
Elective CABG
LVEF (%) < 50%,
Gastrointestinal disorders,
Diabetes
Splanchnic oxygenation,
Systemic inflammation, Subsequent acute-phase response.
Unspecified
Shi YF [48]
Journal of Thoracic and Cardiovascular Surgery
2006
Elective CABG
Placebo
Elective CABG
Had pacemaker or not in sinus rhythm
Biventricular filling properties
Unspecified
Song JW [49]
Korean Journal of Anesthesiology
2011
Elective CABG (off-pump)
Placebo
E/e’ value > 15
Concomitant systolic dysfunction,
Mitral regurgitation ≥ Grade 2,
Emergency operation.
Hemodynamics and short term outcomes
Unspecified
Yamaguchi A [50]
Annals Of Thoracic And Cardiovascular Surgery
2009
Elective CABG and valvular surgery
Standard treatment
Elective CABG concomitant LVR,
LV dysfunction (LVEF (%) < 30%),
LVESVI > 100 ml/m2
Unspecified
Left ventricular restoration
Unspecified
Yamaura K [51]
Journal of Cardiothoracic and Vascular Anesthesia
2001
Elective CABG
Standard treatment
Cardiac Surgery
Unspecified
Gastric intramucosal pH,
Systemic inflammation
Unspecified
Abbreviations: CABG coronary artery bypass grafting, LVEF left ventricular ejection fraction, TEE transesophageal echocardiography, PAP pulmonary arterial pressure, AF atrial fibrillation, MI myocardial infarction, E/e’ the ratio of the early transmitral flow velocity to the early diastolic velocity of the mitral annulus, LVR left ventricular restoration, LVESVI left ventricular end-systolic volume index

Study characteristics

The total number of patients in the 16 included trials was 698, who underwent CABG surgery (346 treated with placebo/standard care and 352 treated with milrinone) (Table 2 and Table 3). In five of these studies, off-pump CABG surgery was performed [31, 40, 44, 45, 53], and on-pump CABG surgery was performed in 11 studies [3844, 47, 53, 55, 56]. As the result showed, the mortality of on-pump CABG between milrinone treatment and placebo/standard care groups, the occurrence was [5/139 (3.59%) vs. 4/146 (2.74%), odds ratio (OR) = 1.17 (0.37–3.72), p value = 0.649, I-squared = 0.0%]. In contrast, off pump GABG was [6/216 (2.78%) vs. 5/205 (2.44%), odds ratio (OR) = 1.00 (0.14–7.30), p value = 1.00, I-squared = 0.0%]. The overall odds ratio (OR) = 1.12 (0.41–3.06), p value = 0.869, I-squared = 0.0%. All these results showed that the mortality occurrences were no significantly difference between on-pump and off-pump CABG surgery. The modes of administration included bolus administration [3842, 44, 47, 53] and continuous infusion [3941, 4851, 5360], which was preceded in 7 studies by an initial bolus [3941, 44, 47, 53] in which the dose of the bolus varied from 30 to 75 μg/kg, and the dose of the continuous infusion varied from 0.25 to 0.75 μg/kg/min. The quality of the current results was variable. Although 3 RCTs were considered high quality, there were a large number of studies lacking important details needed for evaluating the risk of selection, performance, attrition, or detection biases (Fig. 2).
Table 2
Baseline Characteristics and Interventions of Included Trials
Author
Group
Patients
Age
Sex
Time of administration
Milrinone dose
Length of infusion
Duration of follow-up
 
(n)
(y)
(M/F)
Bolus
Infusion
Arbeus M [38]
MIL
22
63 ± 10
20/2
After release of aortic clamp
50 μg/kg
None
Bolus only
Hospital Stay
Ctrl
22
62 ± 9
17/5
Couture P [39]
MIL
25
67 ± 8
19/6
After anesthesia induction
50 μg/kg
0.5 μg/kg/min
Until skin closure
Hospital Stay
Ctrl
25
70 ± 7
19/6
Doolan LA [40]
MIL
15
65 ± 10.4
14/1
15 min before weaning from CPB
50 μg/kg
0.5 μg/kg/min
4 h or longer
30 day
Ctrl
15
67 ± 8.6
14/1
Guo YJ [9]
MIL
31
56 ± 6
21/10
After release of aortic clamp
50 μg/kg
0.5 μg/kg/min
24 h
Hospital Stay
Ctrl
31
54 ± 6
20/11
Hadadzadeh M [41]
MIL
40
62 ± 10.7
31/9
After anesthesia induction
50 μg/kg
0.5 μg/kg/min
24 h
ICU Stay
Ctrl
40
63 ± 9.6
26/14
Hamada Y [42]
MIL
10
66.2 ± 8.1
6/4
After release of aortic clamp
50 μg/kg
None
Bolus only
Operating Room
Ctrl
10
62.4 ± 6.5
6/4
Hayashida N [43]
MIL
12
63.3 ± 2.8
7/5
After anesthesia induction
None
0.5 μg/kg/min
24 h
72 h
Ctrl
12
62.7 ± 2.8
9/3
Jebeli M [44]
MIL
35
56.9 ± 9.7
25/10
After release of aortic clamp
50 μg/kg
0.5 μg/kg/min
24 h
Hospital Stay
Ctrl
35
58.2 ± 8.4
28/7
Jo HR [45]
MIL
20
67.0 ± 9.2
12/8
After sternotomy
None
0.5 μg/kg/min
Until skin closure
Hospital Stay
Ctrl
20
64.1 ± 9.9
11/9
Kwak YL [46]
MIL
29
61.5 ± 8.2
21/8
After IMA harvest
None
0.5 μg/kg/min
End of anastomosis
Hospital Stay
Ctrl
33
60.4 ± 8.4
26/7
Lee JH [32]
MIL
24
63 ± 8
20/4
After sternotomy
None
0.5 μg/kg/min
Until skin closure
Hospital Stay
Ctrl
26
62 ± 8
20/6
Möllhoff T [47]
MIL
11
60 ± 8
Not specified
After anesthesia induction
30 μg/kg
0.5 μg/kg/min
Unspecified
1 Year
Ctrl
11
61 ± 6
Shi Y [53]
MIL
25
Not specified
Not specified
After anesthesia induction
50 μg/kg
0.5 μg/kg/min
Until skin closure
6 month
Ctrl
24
High: 75 μg/kg
High: 0.75 μg/kg/min
Song JW [54]
MIL
31
67.2 ± 7.6
14/17
After harvesting the left
None
0.5 μg/kg/min
31 ± 7 min
Hospital Stay
Ctrl
31
65.7 ± 7.9
21/10
internal mammary artery
Yamaguchi A [55]
MIL
14
64.1 ± 8
13/1
After induction of CPB
None
0.5 μg/kg/min
48 h
ICU Stay
Ctrl
14
65.2 ± 8.5
13/1
Yamaura K [56]
MIL
10
66 ± 6
7/3
After induction of CPB
None
0.25 μg/kg/min
1 h after in ICU
Hospital Stay
Ctrl
10
57 ± 16
6/4
Table 3
Preoperative Ejection Fraction and Postoperative Causes of Death in the 2 Groups
First Author
Preoperative EF (MIL Group)
Preoperative EF (Ctrl Group)
No. of Death
(Death/Total, MIL Group)
No. of Death (Death/Total, Ctrl Group)
Cause of Death (MIL Group)
Cause of Death (Ctrl Group)
Adverse Effects (MIL Group)
Adverse Effects (Ctrl Group)
Arbeus [38]
59 ± 12
63 ± 9
1
22
0
22
Not specified
No death
No adverse events or side effects
Couture [39]
51 ± 15
50 ± 13
2
25
0
25
Multiple organ failure (2)
No death
Acute renal failure (2)
Acute renal failure (1)
Doolan [40]
Not specified
Not specified
0
15
0
15
No death
No death
No adverse events or side effects
Guo [9]
35 ± 4
35 ± 5
1
31
1
31
Not specified
Not specified
Not specified
Hadadzadeh [41]
29 ± 5.5
28.6 ± 5.6
1
40
1
40
Cardiac shock
Cardiac shock
CVA,
Renal failure (1)
CVA,
Renal failure (3)
Hamada [42]
Not specified
Not specified
0
20
0
10
No death
No death
No adverse events or side effects
Hayashida [43]
Not specified
Not specified
0
12
0
12
No death
No death
No serious adverse effects
Low output syndrome (1)
Jebeli [44]
31.8 ± 3.2
34.5 ± 1.4
0
35
2
35
No death
Cardiogenic shock (2)
No adverse events or side effects
Jo [45]
45 ± 14
51 ± 13
0
20
0
20
No death
No death
Renal failure (1)
Renal failure (2)
Kwak [46]
Not specified
Not specified
0
29
0
33
No death
No death
No adverse events or side effects
Lee [32]
50 ± 17
57 ± 8
0
24
0
26
No death
No death
No adverse events or side effects
Möllhoff [47]
Not specified
Not specified
0
11
0
11
No death
No death
No adverse events or side effects
Shi [53]
Not specified
Not specified
1
25
1
24
Not specified
Not specified
Not specified
Song [54]
55.3 ± 15.3
51.5 ± 16.7
1
31
1
31
Not specified
Not specified
Not specified
Yamaguchi [55]
64.1 ± 8
65.2 ± 8.5
0
14
0
14
No death
No death
Not specified
Yamaura [56]
Not specified
Not specified
0
10
0
10
No death
No death
No adverse events or side effects

Quantitative data synthesis

The overall analysis demonstrated that the mortality rate was not higher in patients receiving milrinone than in patients receiving placebo/standard care [11/352 (3.13%): mortality in the milrinone treatment group 9/346 (2.60%) versus mortality in the control group, RR = 1.18 (0.53–2.62), p value = 0.69, p for heterogeneity = 0.91, I2 = 0%] (Fig. 3).
Sensitivity analysis and funnel plot inspection confirmed the overall robustness of the present findings and the lack of evidence of small-study bias, respectively (Fig. 5a).
The subanalysis of different postoperative outcomes (Fig. 4, Table 4) showed a statistically significant effect of milrinone on reducing the occurrence of MI [5/219 (2.28%) in the milrinone treatment group versus 25/221 (11.31%) in the control group, RR = 0.23 (0.10–0.54), p value = 0.0008, p for heterogeneity = 0.35, I2 = 9%, with 9 studies included], myocardial ischemia [12/106 (11.32%) in the milrinone treatment group vs. 41/106 (36.68%) in the control group, RR = 0.29 (0.16–0.52), p value < 0.0001, p for heterogeneity = 0.55, I2 = 0%, with 3 studies included], and arrhythmia [16/234 (6.84%) in the milrinone treatment group vs. 31/236 (13.14%) in the control group, RR = 0.53 (0.31–0.91), p value = 0.02, p for heterogeneity = 0.55, I2 = 0%, with 10 studies included].
Table 4
A Summary of the Global Effect of Different Outcomes
 
Patients (Studies) Included
Milrinone: Events (%)
Control: Events (%)
RR
95% CI
p for Effect
I2 (p for heterogeneity)
Myocardical Infarction
440 (30)
5 (2.28%)
25 (11.31%)
0.23
0.10–0.54
0.0008
9% (0.35)
Myocardial Ischemia
212 (53)
12 (11.32)
41 (36.68)
0.29
0.16–0.52
<  0.0001
0% (0.55)
Arrhythmias
470 (47)
16 (6.84)
31 (13.14)
0.53
0.31–0.91
0.02
0% (0.55)
Stroke
172 (2)
2 (2.33)
0 (0)
3.00
0.32–27.88
0.33
0% (1.00)
Renal Failure
302 (17)
9 (5.96)
8 (5.30)
1.25
0.45–2.81
0.80
0% (0.64)
Another subanalysis showed a difference in the risk of stroke [2/86 (2.33%) in the milrinone treatment group vs. 0/86 (0%) in the control group, RR = 3.00 (0.32–27.88), p value = 0.33, p for heterogeneity = 1.00, I2 = 0%, with 3 studies included] and renal failure [9/151 (5.96%) in the milrinone treatment group vs. 8/151 (5.30%) in the control group, RR = 1.25 (0.45–2.81), p for effect = 0.80, p for heterogeneity = 0.64, I2 = 0%, with 5 studies included]. Sensitivity analysis and funnel plot inspection confirmed the overall robustness of the present findings and the lack of evidence of small-study bias, respectively (Fig. 5b).

Meta-regression

Meta-regression was used to analyze potential causes for heterogeneity on one-year mortality. The results showed that there were not statistically significant for sample size, mean number of grafts, mean pump time, mean AoXclamp time, mean pre-op LVEF, post-op inotropes, pre-op shock/MI, and post-op IABP (Tables 5 and 6). All these parameters were not associated with mortality.
Table 5
The meta-regression analyses
Parameter
Regression
P value
Sample size
y = 0.0022x + 0.0603
0.9488
Mean number of grafts
y = −0.0368x + 0.2930
0.9926
Mean pump time
y = 0.0092x + 1.0395
0.6035
Mean AoXclamp time
y = −0.0091x + 0.9190
0.6505
Mean preop LVEF
y = 0.0160x - 0.4410
0.6420
Postop inotropes
y = −0.0629x + 1.3785
0.2812
Preop shock/MI
y = −0.0263x + 0.2877
0.7811
Postop IABP
y = −0.1269x - 0.7856
0.5557
Table 6
The meta-regression analyses of preop drugs
Preop drugs
Regression
P value
ACE inhibitors
y = − 0.0713x + 1.3446
0.6860
Calcium channel inhibitors
y = − 0.0396x + 1.1287
0.6836
Diuretics
y = − 0.0066x + 0.0849
0.9734
Nitrates
y = 0.0997x - 0.6147
0.6246
β-receptor inhibitors
y = 0.0128x + 0.2710
0.8870

Discussion

In this study, we conducted a systematic meta-analysis of all existing, enrolled and randomized studies comparing milrinone treatment to placebo/standard care in patients who underwent CABG surgery. The results showed that compared with placebo treatment, milrinone treatment did not contribute to mortality. Although milrinone failed to reduce mortality, the risk of postoperative complications, such as MI, myocardial ischemia, and arrhythmia, was significantly decreased when patients underwent CABG surgery.
Approximately 110 million people are affected by CAD, which resulted in 8.9 million deaths in 2015 [56]. CAD is considered the most common cause of death globally because of its high mortality risk (15.9%) [57]. From 1980 to 2010, the number of cases and the risk of death from CAD for a given age both declined, especially in developed countries [58, 59]. Some well-determined risk factors, including high blood pressure, smoking, diabetes, obesity, family history, and excessive alcohol, were controlled. Approximately half of the cases result from genetics among all these factors [48, 49, 60]. Obesity and smoking are associated approximately 20 and 36% of cases, respectively [50]. The typical pathophysiological characteristic of CAD is limited blood flow to the heart, which may result in ischemia and long-term oxygen deficiencies in heart muscle, leading to cell death and, ultimately, causing myocardial infarction (MI). In addition, transient ischemia resulting from coronary artery stenosis may lead to ventricular arrhythmia, devolve into a dangerous heart rhythm, and lead to death, which is known as ventricular fibrillation [51]. Although a Cochrane review in 2015 suggested that combining preventive strategies such as persisting appropriate physical exercise, maintaining a healthy diet, treating hypertension, reducing cholesterol and quitting smoking could effectively prevent the risk of CAD [6165]. there was insufficient evidence to prove an impact on mortality or actual cardiovascular events [66]. Until now, the most effective treatment options for moderate to severe CAD have been medications (such as statins, nitroglycerin, calcium channel blockers, and/or beta-blockers and aspirin) [6769] and surgery (such as CABG surgery) [7072]. CABG surgery is performed to treat coronary artery disease (CAD) by using a grafted vein to establish vascular access between the root of the ascending aorta and the distal end of the lesion site so that blood can bypass the coronary artery lesion site and reach the ischemic myocardium, thus improving coronary perfusion and increasing myocardial oxygen supply, which is also called myocardial revascularization [73, 74]. Numerous studies have demonstrated that CABG surgery is associated with low mortality (in both the short term and the long term) as well as cognitive and renal function benefits [75, 76]. In the past decade, percutaneous coronary intervention (PCI) has been increased to treat unprotected left main coronary artery disease. PCI can be selectively performed in patients who are candidates for revascularization but who are ineligible for CABG. Compared with CABG, PCI with stenting has a similar mortality but higher rates of myocardial infarction and repeat revascularisation in patients with left main coronary artery disease. So current guidelines recommend CABG as the treatment of choice for patients with asymptomatic ischemia, stable angina, or unstable angina/non-ST elevation myocardial infarction who have left main coronary artery disease [77, 78]. However, multiple complications (including MI, myocardial ischemia, arrhythmia, stroke, and kidney failure) are common postoperative syndromes after CABG [7, 17, 19, 20, 79]. Surgery, combined with medication pre- and/or postoperatively, such as inotropic agents, which can increase myocardial contractility that results, in most cases, in increasing intracellular cAMP levels, can effectively avoid or ameliorate these unwanted outcomes [8082]. Increased cAMP subsequently stimulates adenylate cyclase and inhibits PDE III simultaneously [83]. Despite (or because of) their effectiveness, inotropic agents face various substantial limitations, such as acute myocardial β-adrenergic receptor desensitization, limiting the function for post-bypass cardiac failure [84]; additional observational data suggest that inotropic agents contribute to worse clinical outcomes due to the high incidence of renal dysfunction and death ratio [8588].
PDE III inhibitors such as milrinone provide an alternative option to inotropic support [84] because they have not only positive inotropic effects but also vasodilatory effects [83, 89]. The preemptive use of milrinone has been beneficial for renal tubular injury [85]. Unlike dobutamine, milrinone does not increase heart rate or myocardial oxygen consumption [90], and some studies have reported that milrinone can significantly reduce the risk of postoperative myocardial ischemia and infarction in patients undergoing CABG surgery [43]. However, one of the current controversies or unknown questions in terms of milrinone application is whether the drug is associated with mortality. A recent meta-analysis by Zangrillo A et al. [34] showed that compared with control agents, milrinone had a tendency to increase mortality and the incidence of arrhythmia in patients who underwent cardiac surgery [13/249 (5.2%) in milrinone vs. 6/269 (2.2%) in the control arm, OR = 2.67 (1.05–6.79), p for effect = 0.04, p for heterogeneity = 0.23, I2 = 25%). However, in their study, 13 trials were included that involved different control agents (3 with levosimendan, 2 with nesiritide, 7 with placebo, and 1 with nothing). These factors may have induced a bias risk. For instance, a subanalysis with placebo or nothing as a control demonstrated no difference in the risk of mortality [4/165 (2.4%) with milrinone vs. 3/164 (1.8%) in the control arm, OR = 1.27 (0.28–5.84), p for effect = 0.76, p for heterogeneity = 0.45, I2 = 0%, 329 patients and 8 studies included]. In addition, an updated meta-analysis [34] showed that neither the overall nor the subgroup (adult patients) mortality in the milrinone-treated group was significantly different from that in the control group (mortality, 2.2% vs. 2.1%, p = 0.70 overall, 3% vs. 2.4%, p = 0.70 in adult patients). However, the sensitivity analysis with a low risk of bias showed a trend, but not statistical significance, toward an increase in mortality with milrinone [8/153 (5.2%) in the milrinone arm vs. 2/152 (1.3%) in the control arm, RR = 2.71 (0.82–9), p for effect = 0.10]. Furthermore, the most recent studies published in 2015 [91] and 2016 [92] demonstrated that there were no differences in mortality in patients administered milrinone compared to the control groups. All these reasons may induce a bias risk.
To avoid these interference factors, we enrolled 16 trials with a randomized total of 698 patients undergoing CABG surgery (346 treated with placebo or standard care and 352 treated with milrinone); the results showed that there was no difference in mortality between the group receiving milrinone and the placebo/standard care group. Nevertheless, the subanalysis demonstrated that the occurrence of myocardial infarction, myocardial ischemia, and arrhythmia decreased significantly with milrinone treatment compared to the placebo or standard care group. However, the occurrence of stroke and renal failure, need for IABP, and duration of inotropic support (h) and mechanical ventilation (h) between these two groups showed no differences. Milrinone was introduced as an agent that causes reduced left and right heart-filling pressures due to its greater reduction in vascular resistance, and it has been used in the treatment of low cardiac output syndrome following cardiac surgery. In the meta-analysis of patients with myocardial infarction suffering from CABG surgery, milrinone was used at any dose and administration time. Mortality after milrinone treatment was not improved despite reductions in important cardiovascular (CV) endpoints. Although the results and conclusions were associated with those of other studies, there may be several reasons for the presented results. First, the association between bias risk and estimates of intervention effects was ignored. Second, the number of included patients was still far too small to draw any firm conclusions. Third, the indications for CABG surgery are relatively extensive. We did not classify the causes of CABG surgery in detail. Therefore, in future studies, additional trial details need to be considered.
Although the evidence in the present study demonstrated that milrinone failed to show an advantage in mortality in adult CABG patients, it significantly reduced the occurrence of MI, myocardial ischemia, and arrhythmia compared to the placebo. All these findings may be helpful for the clinical application of milrinone and may provide therapeutic strategies for CABG surgery. Furthermore, along with clinical milrinone application, sufficient data from randomized clinical trials need to be collected, and the potential benefits or adverse effects should be analyzed and reevaluated.

Limitations

Our study has several limitations. First, the authors acknowledge that only 4 of the 16 studies included in this meta-analysis were of high quality. Second, in the enrolled RCTs, the doses of milrinone were between 30 and 75 μg/kg (as an intravenous bolus) and between 0.5 and 0.75 μg/kg/min (as continuous infusion). This fact suggests that the current reference lacks generalizability of milrinone at doses beyond the range of 0.3–0.75 μg/kg/min. Third, our study on the incidence of myocardial ischemia, stroke, and renal failure was performed using a small number of studies and patients. Therefore, the current results are not conclusive due to the possibility of induced error. Finally, only one trial was evaluated with a 1-year follow-up, so deficits in the short follow-up could have potentially impacted our mortality analyses.

Conclusions

This meta-analysis suggests that, compared to placebo or standard care, milrinone neither significantly increases nor decreases the risk of dying in adult patients undergoing CABG surgery, but milrinone can efficiently ameliorate the incidence of postoperative complications, including MI, myocardial ischemia, and arrhythmia.

Acknowledgements

Not applicable.

Declarations

Not applicable.
Not applicable.
Not applicable.

Competing interests

The authors declare that they have no competing interests.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Literatur
1.
Zurück zum Zitat Wong ND. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol. 2014;11(5):276–89.PubMed Wong ND. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol. 2014;11(5):276–89.PubMed
2.
Zurück zum Zitat Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association scientific statement on obesity and heart disease from the obesity Committee of the Council on nutrition, physical activity, and metabolism. Circulation. 2006;113(6):898–918.PubMed Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association scientific statement on obesity and heart disease from the obesity Committee of the Council on nutrition, physical activity, and metabolism. Circulation. 2006;113(6):898–918.PubMed
3.
Zurück zum Zitat Borghi C, Omboni S, Reggiardo G, Bacchelli S, Degli Esposti D, Ambrosioni E. Efficacy of Zofenopril compared with placebo and other angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction and previous cardiovascular risk factors: a pooled individual data analysis of 4 randomized, double-blind, controlled, prospective studies. J Cardiovasc Pharmacol. 2017;69(1):48–54.PubMedPubMedCentral Borghi C, Omboni S, Reggiardo G, Bacchelli S, Degli Esposti D, Ambrosioni E. Efficacy of Zofenopril compared with placebo and other angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction and previous cardiovascular risk factors: a pooled individual data analysis of 4 randomized, double-blind, controlled, prospective studies. J Cardiovasc Pharmacol. 2017;69(1):48–54.PubMedPubMedCentral
4.
Zurück zum Zitat Menendez ME, Memtsoudis SG, Opperer M, Boettner F, Gonzalez Della Valle A. A nationwide analysis of risk factors for in-hospital myocardial infarction after total joint arthroplasty. Int Orthop. 2015;39(4):777–86.PubMed Menendez ME, Memtsoudis SG, Opperer M, Boettner F, Gonzalez Della Valle A. A nationwide analysis of risk factors for in-hospital myocardial infarction after total joint arthroplasty. Int Orthop. 2015;39(4):777–86.PubMed
5.
Zurück zum Zitat Braunwald E. Treatment of left Main coronary artery disease. N Engl J Med. 2016;375(23):2284–5.PubMed Braunwald E. Treatment of left Main coronary artery disease. N Engl J Med. 2016;375(23):2284–5.PubMed
6.
Zurück zum Zitat Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL. Everolimus-eluting stents or bypass surgery for multivessel coronary disease. N Engl J Med. 2015;372(13):1213–22.PubMed Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL. Everolimus-eluting stents or bypass surgery for multivessel coronary disease. N Engl J Med. 2015;372(13):1213–22.PubMed
7.
Zurück zum Zitat Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med. 2015;373(15):1408–17.PubMed Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med. 2015;373(15):1408–17.PubMed
8.
Zurück zum Zitat Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL. Revascularization in patients with multivessel coronary artery disease and chronic kidney disease: Everolimus-eluting stents versus coronary artery bypass graft surgery. J Am Coll Cardiol. 2015;66(11):1209–20.PubMedPubMedCentral Bangalore S, Guo Y, Samadashvili Z, Blecker S, Xu J, Hannan EL. Revascularization in patients with multivessel coronary artery disease and chronic kidney disease: Everolimus-eluting stents versus coronary artery bypass graft surgery. J Am Coll Cardiol. 2015;66(11):1209–20.PubMedPubMedCentral
9.
Zurück zum Zitat Aldea GS, Bakaeen FG, Pal J, Fremes S, Head SJ, Sabik J, Rosengart T, Kappetein AP, Thourani VH, Firestone S, et al. The Society of Thoracic Surgeons clinical practice guidelines on arterial conduits for coronary artery bypass grafting. Ann Thorac Surg. 2016;101(2):801–9.PubMed Aldea GS, Bakaeen FG, Pal J, Fremes S, Head SJ, Sabik J, Rosengart T, Kappetein AP, Thourani VH, Firestone S, et al. The Society of Thoracic Surgeons clinical practice guidelines on arterial conduits for coronary artery bypass grafting. Ann Thorac Surg. 2016;101(2):801–9.PubMed
10.
Zurück zum Zitat Shafarenko MS, Catapano J, Luo S, Zuker RM, Van Arsdell G, Borschel GH. Outcomes following coronary artery bypass grafting with microsurgery in paediatric patients. Interact Cardiovasc Thorac Surg. 2018;27(1):27–33.PubMed Shafarenko MS, Catapano J, Luo S, Zuker RM, Van Arsdell G, Borschel GH. Outcomes following coronary artery bypass grafting with microsurgery in paediatric patients. Interact Cardiovasc Thorac Surg. 2018;27(1):27–33.PubMed
11.
Zurück zum Zitat Amin S, Werner RS, Madsen PL, Krasopoulos G, Taggart DP. Influence of external stenting on venous graft flow parameters in coronary artery bypass grafting: a randomized study. Interact Cardiovasc Thorac Surg. 2018;26(6):926–31.PubMed Amin S, Werner RS, Madsen PL, Krasopoulos G, Taggart DP. Influence of external stenting on venous graft flow parameters in coronary artery bypass grafting: a randomized study. Interact Cardiovasc Thorac Surg. 2018;26(6):926–31.PubMed
12.
Zurück zum Zitat Gordon JB, Daniels LB, Kahn AM, Jimenez-Fernandez S, Vejar M, Numano F, Burns JC. The Spectrum of cardiovascular lesions requiring intervention in adults after Kawasaki disease. JACC Cardiovasc Interv. 2016;9(7):687–96.PubMed Gordon JB, Daniels LB, Kahn AM, Jimenez-Fernandez S, Vejar M, Numano F, Burns JC. The Spectrum of cardiovascular lesions requiring intervention in adults after Kawasaki disease. JACC Cardiovasc Interv. 2016;9(7):687–96.PubMed
13.
Zurück zum Zitat Laukkanen JA, Kunutsor SK, Niemela M, Kervinen K, Thuesen L, Makikallio TH. All-cause mortality and major cardiovascular outcomes comparing percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: a meta-analysis of short-term and long-term randomised trials. Open Heart. 2017;4(2):e000638.PubMedPubMedCentral Laukkanen JA, Kunutsor SK, Niemela M, Kervinen K, Thuesen L, Makikallio TH. All-cause mortality and major cardiovascular outcomes comparing percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: a meta-analysis of short-term and long-term randomised trials. Open Heart. 2017;4(2):e000638.PubMedPubMedCentral
14.
Zurück zum Zitat Badheka AO, Panaich SS, Arora S, Patel N, Patel NJ, Savani C, Deshmukh A, Cohen MG. Percutaneous coronary intervention: relationship between procedural volume and outcomes. Curr Cardiol Rep. 2016;18(4):39.PubMed Badheka AO, Panaich SS, Arora S, Patel N, Patel NJ, Savani C, Deshmukh A, Cohen MG. Percutaneous coronary intervention: relationship between procedural volume and outcomes. Curr Cardiol Rep. 2016;18(4):39.PubMed
15.
Zurück zum Zitat Hannan EL, Farrell LS, Walford G, Berger PB, Stamato NJ, Venditti FJ, Jacobs AK, Holmes DR Jr, Sharma S, King SB 3rd. Utilization of radial artery access for percutaneous coronary intervention for ST-segment elevation myocardial infarction in New York. JACC Cardiovasc Interv. 2014;7(3):276–83.PubMed Hannan EL, Farrell LS, Walford G, Berger PB, Stamato NJ, Venditti FJ, Jacobs AK, Holmes DR Jr, Sharma S, King SB 3rd. Utilization of radial artery access for percutaneous coronary intervention for ST-segment elevation myocardial infarction in New York. JACC Cardiovasc Interv. 2014;7(3):276–83.PubMed
16.
Zurück zum Zitat Hye RJ, Voeks JH, Malas MB, Tom M, Longson S, Blackshear JL, Brott TG. Anesthetic type and risk of myocardial infarction after carotid endarterectomy in the carotid revascularization Endarterectomy versus stenting trial (CREST). J Vasc Surg. 2016;64(1):3–8 e1.PubMedPubMedCentral Hye RJ, Voeks JH, Malas MB, Tom M, Longson S, Blackshear JL, Brott TG. Anesthetic type and risk of myocardial infarction after carotid endarterectomy in the carotid revascularization Endarterectomy versus stenting trial (CREST). J Vasc Surg. 2016;64(1):3–8 e1.PubMedPubMedCentral
17.
Zurück zum Zitat Yamanaka T, Kawai Y, Miyoshi T, Mima T, Takagaki K, Tsukuda S, Kazatani Y, Nakamura K, Ito H. Remote ischemic preconditioning reduces contrast-induced acute kidney injury in patients with ST-elevation myocardial infarction: a randomized controlled trial. Int J Cardiol. 2015;178:136–41.PubMed Yamanaka T, Kawai Y, Miyoshi T, Mima T, Takagaki K, Tsukuda S, Kazatani Y, Nakamura K, Ito H. Remote ischemic preconditioning reduces contrast-induced acute kidney injury in patients with ST-elevation myocardial infarction: a randomized controlled trial. Int J Cardiol. 2015;178:136–41.PubMed
18.
Zurück zum Zitat Nishizawa K, Yano T, Tanno M, Miki T, Kuno A, Tobisawa T, Ogasawara M, Muratsubaki S, Ohno K, Ishikawa S, et al. Chronic treatment with an erythropoietin receptor ligand prevents chronic kidney disease-induced enlargement of myocardial infarct size. Hypertension. 2016;68(3):697–706.PubMed Nishizawa K, Yano T, Tanno M, Miki T, Kuno A, Tobisawa T, Ogasawara M, Muratsubaki S, Ohno K, Ishikawa S, et al. Chronic treatment with an erythropoietin receptor ligand prevents chronic kidney disease-induced enlargement of myocardial infarct size. Hypertension. 2016;68(3):697–706.PubMed
19.
Zurück zum Zitat Lee WC, Fang HY, Chen HC, Chen CJ, Yang CH, Hang CL, Wu CJ, Fang CY. Anemia: a significant cardiovascular mortality risk after ST-segment elevation myocardial infarction complicated by the comorbidities of hypertension and kidney disease. PLoS One. 2017;12(7):e0180165.PubMedPubMedCentral Lee WC, Fang HY, Chen HC, Chen CJ, Yang CH, Hang CL, Wu CJ, Fang CY. Anemia: a significant cardiovascular mortality risk after ST-segment elevation myocardial infarction complicated by the comorbidities of hypertension and kidney disease. PLoS One. 2017;12(7):e0180165.PubMedPubMedCentral
20.
Zurück zum Zitat Hansen MK, Gammelager H, Jacobsen CJ, Hjortdal VE, Layton JB, Rasmussen BS, Andreasen JJ, Johnsen SP, Christiansen CF. Acute kidney injury and long-term risk of cardiovascular events after cardiac surgery: a population-based cohort study. J Cardiothorac Vasc Anesth. 2015;29(3):617–25.PubMed Hansen MK, Gammelager H, Jacobsen CJ, Hjortdal VE, Layton JB, Rasmussen BS, Andreasen JJ, Johnsen SP, Christiansen CF. Acute kidney injury and long-term risk of cardiovascular events after cardiac surgery: a population-based cohort study. J Cardiothorac Vasc Anesth. 2015;29(3):617–25.PubMed
21.
Zurück zum Zitat Nojiri T, Yamamoto K, Maeda H, Takeuchi Y, Ose N, Susaki Y, Inoue M, Okumura M. A double-blind placebo-controlled study of the effects of Olprinone, a specific Phosphodiesterase III inhibitor, for preventing postoperative atrial fibrillation in patients undergoing pulmonary resection for lung Cancer. Chest. 2015;148(5):1285–92.PubMed Nojiri T, Yamamoto K, Maeda H, Takeuchi Y, Ose N, Susaki Y, Inoue M, Okumura M. A double-blind placebo-controlled study of the effects of Olprinone, a specific Phosphodiesterase III inhibitor, for preventing postoperative atrial fibrillation in patients undergoing pulmonary resection for lung Cancer. Chest. 2015;148(5):1285–92.PubMed
22.
Zurück zum Zitat Brown DG, Wilkerson EC, Love WE. A review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons. J Am Acad Dermatol. 2015;72(3):524–34.PubMed Brown DG, Wilkerson EC, Love WE. A review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons. J Am Acad Dermatol. 2015;72(3):524–34.PubMed
23.
Zurück zum Zitat Karibe H, Hayashi T, Narisawa A, Kameyama M, Nakagawa A, Tominaga T. Clinical characteristics and outcome in elderly patients with traumatic brain injury: for establishment of management strategy. Neurol Med Chir. 2017;57(8):418–25. Karibe H, Hayashi T, Narisawa A, Kameyama M, Nakagawa A, Tominaga T. Clinical characteristics and outcome in elderly patients with traumatic brain injury: for establishment of management strategy. Neurol Med Chir. 2017;57(8):418–25.
24.
Zurück zum Zitat Harrison SA, Chang ML, Beavo JA. Differential inhibition of cardiac cyclic nucleotide phosphodiesterase isozymes by cardiotonic drugs. Circulation. 1986;73(3 Pt 2):III109–16.PubMed Harrison SA, Chang ML, Beavo JA. Differential inhibition of cardiac cyclic nucleotide phosphodiesterase isozymes by cardiotonic drugs. Circulation. 1986;73(3 Pt 2):III109–16.PubMed
25.
Zurück zum Zitat Shipley JB, Tolman D, Hastillo A, Hess ML. Milrinone: basic and clinical pharmacology and acute and chronic management. Am J Med Sci. 1996;311(6):286–91.PubMed Shipley JB, Tolman D, Hastillo A, Hess ML. Milrinone: basic and clinical pharmacology and acute and chronic management. Am J Med Sci. 1996;311(6):286–91.PubMed
26.
Zurück zum Zitat Endoh M, Yamashita S, Taira N. Positive inotropic effect of amrinone in relation to cyclic nucleotide metabolism in the canine ventricular muscle. J Pharmacol Exp Ther. 1982;221(3):775–83.PubMed Endoh M, Yamashita S, Taira N. Positive inotropic effect of amrinone in relation to cyclic nucleotide metabolism in the canine ventricular muscle. J Pharmacol Exp Ther. 1982;221(3):775–83.PubMed
27.
Zurück zum Zitat Endoh M, Yanagisawa T, Taira N, Blinks JR. Effects of new inotropic agents on cyclic nucleotide metabolism and calcium transients in canine ventricular muscle. Circulation. 1986;73(3 Pt 2):III117–33.PubMed Endoh M, Yanagisawa T, Taira N, Blinks JR. Effects of new inotropic agents on cyclic nucleotide metabolism and calcium transients in canine ventricular muscle. Circulation. 1986;73(3 Pt 2):III117–33.PubMed
28.
Zurück zum Zitat Levy JH, Bailey JM, Deeb GM. Intravenous milrinone in cardiac surgery. Ann Thorac Surg. 2002;73(1):325–30.PubMed Levy JH, Bailey JM, Deeb GM. Intravenous milrinone in cardiac surgery. Ann Thorac Surg. 2002;73(1):325–30.PubMed
29.
Zurück zum Zitat Chen EP, Bittner HB, Davis RD Jr, Van Trigt P 3rd. Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension. Ann Thorac Surg. 1997;63(3):814–21.PubMed Chen EP, Bittner HB, Davis RD Jr, Van Trigt P 3rd. Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension. Ann Thorac Surg. 1997;63(3):814–21.PubMed
30.
Zurück zum Zitat Kwak YL, Oh YJ, Shinn HK, Yoo KJ, Kim SH, Hong YW. Haemodynamic effects of a milrinone infusion without a bolus in patients undergoing off-pump coronary artery bypass graft surgery. Anaesthesia. 2004;59(4):324–31.PubMed Kwak YL, Oh YJ, Shinn HK, Yoo KJ, Kim SH, Hong YW. Haemodynamic effects of a milrinone infusion without a bolus in patients undergoing off-pump coronary artery bypass graft surgery. Anaesthesia. 2004;59(4):324–31.PubMed
31.
Zurück zum Zitat Lee JH, Oh YJ, Shim YH, Hong YW, Yi G, Kwak YL. The effect of milrinone on the right ventricular function in patients with reduced right ventricular function undergoing off-pump coronary artery bypass graft surgery. J Korean Med Sci. 2006;21(5):854–8.PubMedPubMedCentral Lee JH, Oh YJ, Shim YH, Hong YW, Yi G, Kwak YL. The effect of milrinone on the right ventricular function in patients with reduced right ventricular function undergoing off-pump coronary artery bypass graft surgery. J Korean Med Sci. 2006;21(5):854–8.PubMedPubMedCentral
32.
Zurück zum Zitat McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the heart failure association (HFA) of the ESC. Eur J Heart Fail. 2012;14(8):803–69.PubMed McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the heart failure association (HFA) of the ESC. Eur J Heart Fail. 2012;14(8):803–69.PubMed
33.
Zurück zum Zitat Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;128(16):1810–52.PubMed Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;128(16):1810–52.PubMed
34.
Zurück zum Zitat Zangrillo A, Biondi-Zoccai G, Ponschab M, Greco M, Corno L, Covello RD, Cabrini L, Bignami E, Melisurgo G, Landoni G. Milrinone and mortality in adult cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth. 2012;26(1):70–7.PubMed Zangrillo A, Biondi-Zoccai G, Ponschab M, Greco M, Corno L, Covello RD, Cabrini L, Bignami E, Melisurgo G, Landoni G. Milrinone and mortality in adult cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth. 2012;26(1):70–7.PubMed
35.
Zurück zum Zitat Majure DT, Greco T, Greco M, Ponschab M, Biondi-Zoccai G, Zangrillo A, Landoni G. Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: an update. J Cardiothorac Vasc Anesth. 2013;27(2):220–9.PubMed Majure DT, Greco T, Greco M, Ponschab M, Biondi-Zoccai G, Zangrillo A, Landoni G. Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: an update. J Cardiothorac Vasc Anesth. 2013;27(2):220–9.PubMed
36.
Zurück zum Zitat Tang X, Liu P, Li R, Jing Q, Lv J, Liu L, Liu Y. Milrinone for the treatment of acute heart failure after acute myocardial infarction: a systematic review and meta-analysis. Basic Clin Pharmacol Toxicol. 2015;117(3):186–94.PubMed Tang X, Liu P, Li R, Jing Q, Lv J, Liu L, Liu Y. Milrinone for the treatment of acute heart failure after acute myocardial infarction: a systematic review and meta-analysis. Basic Clin Pharmacol Toxicol. 2015;117(3):186–94.PubMed
37.
Zurück zum Zitat Koperny M, Lesniak W, Jankowski M, Bala M. The Cochrane collaboration - the role in the evolution of evidence-based medicine and development of cooperation in Poland. Przeglad Epidemiol. 2016;70(3):508–20. Koperny M, Lesniak W, Jankowski M, Bala M. The Cochrane collaboration - the role in the evolution of evidence-based medicine and development of cooperation in Poland. Przeglad Epidemiol. 2016;70(3):508–20.
38.
Zurück zum Zitat Couture P, Denault AY, Pellerin M, Tardif JC. Milrinone enhances systolic, but not diastolic function during coronary artery bypass grafting surgery. Can J Anaesthesia. 2007;54(7):509–22. Couture P, Denault AY, Pellerin M, Tardif JC. Milrinone enhances systolic, but not diastolic function during coronary artery bypass grafting surgery. Can J Anaesthesia. 2007;54(7):509–22.
39.
Zurück zum Zitat Doolan LA, Jones EF, Kalman J, Buxton BF, Tonkin AM. A placebo-controlled trial verifying the efficacy of milrinone in weaning high-risk patients from cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1997;11(1):37–41.PubMed Doolan LA, Jones EF, Kalman J, Buxton BF, Tonkin AM. A placebo-controlled trial verifying the efficacy of milrinone in weaning high-risk patients from cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1997;11(1):37–41.PubMed
40.
Zurück zum Zitat Hadadzadeh M, Hosseini SH, Mostafavi Pour Manshadi SM, Naderi N, Emami Meybodi M. Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial. Acta medica Iranica. 2013;51(10):681–6.PubMed Hadadzadeh M, Hosseini SH, Mostafavi Pour Manshadi SM, Naderi N, Emami Meybodi M. Effect of milrinone on short term outcome of patients with myocardial dysfunction undergoing off-pump coronary artery bypass graft: a randomized clinical trial. Acta medica Iranica. 2013;51(10):681–6.PubMed
41.
Zurück zum Zitat Hamada Y, Kawachi K, Yamamoto T, Nakata T, Kashu Y, Sato M, Watanabe Y. Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone. Jpn Circ J. 1999;63(8):605–9.PubMed Hamada Y, Kawachi K, Yamamoto T, Nakata T, Kashu Y, Sato M, Watanabe Y. Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone. Jpn Circ J. 1999;63(8):605–9.PubMed
42.
Zurück zum Zitat Hayashida N, Tomoeda H, Oda T, Tayama E, Chihara S, Kawara T, Aoyagi S. Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass. Ann Thorac Surg. 1999;68(5):1661–7.PubMed Hayashida N, Tomoeda H, Oda T, Tayama E, Chihara S, Kawara T, Aoyagi S. Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass. Ann Thorac Surg. 1999;68(5):1661–7.PubMed
43.
Zurück zum Zitat Jebeli M, Ghazinoor M, Mandegar MH, Rasouli MR, Eghtesadi-Araghi P, Goodarzynejad H, Mohammadzadeh R, Darehzereshki A, Dianat S. Effect of milrinone on short-term outcome of patients with myocardial dysfunction undergoing coronary artery bypass graft: a randomized controlled trial. Cardiol J. 2010;17(1):73–8.PubMed Jebeli M, Ghazinoor M, Mandegar MH, Rasouli MR, Eghtesadi-Araghi P, Goodarzynejad H, Mohammadzadeh R, Darehzereshki A, Dianat S. Effect of milrinone on short-term outcome of patients with myocardial dysfunction undergoing coronary artery bypass graft: a randomized controlled trial. Cardiol J. 2010;17(1):73–8.PubMed
44.
Zurück zum Zitat Jo HR, Lee WK, Kim YH, Min JH, Chae YK, Choi IG, Kim YS, Lee YK. The effect of milrinone infusion on right ventricular function during coronary anastomosis and early outcomes in patients undergoing off-pump coronary artery bypass surgery. Korean J Anesthesiol. 2010;59(2):92–8.PubMedPubMedCentral Jo HR, Lee WK, Kim YH, Min JH, Chae YK, Choi IG, Kim YS, Lee YK. The effect of milrinone infusion on right ventricular function during coronary anastomosis and early outcomes in patients undergoing off-pump coronary artery bypass surgery. Korean J Anesthesiol. 2010;59(2):92–8.PubMedPubMedCentral
45.
Zurück zum Zitat Kwak YL, Oh YJ, Kim SH, Shin HK, Kim JY, Hong YW. Efficacy of pre-emptive milrinone in off-pump coronary artery bypass surgery: comparison between patients with a low and normal pre-graft cardiac index. Eur J Cardio-Thorac Surg. 2004;26(4):687–93. Kwak YL, Oh YJ, Kim SH, Shin HK, Kim JY, Hong YW. Efficacy of pre-emptive milrinone in off-pump coronary artery bypass surgery: comparison between patients with a low and normal pre-graft cardiac index. Eur J Cardio-Thorac Surg. 2004;26(4):687–93.
46.
Zurück zum Zitat Mollhoff T, Loick HM, Van Aken H, Schmidt C, Rolf N, Tjan TD, Asfour B, Berendes E. Milrinone modulates endotoxemia, systemic inflammation, and subsequent acute phase response after cardiopulmonary bypass (CPB). Anesthesiology. 1999;90(1):72–80.PubMed Mollhoff T, Loick HM, Van Aken H, Schmidt C, Rolf N, Tjan TD, Asfour B, Berendes E. Milrinone modulates endotoxemia, systemic inflammation, and subsequent acute phase response after cardiopulmonary bypass (CPB). Anesthesiology. 1999;90(1):72–80.PubMed
47.
Zurück zum Zitat Shi Y, Denault AY, Couture P, Butnaru A, Carrier M, Tardif JC. Biventricular diastolic filling patterns after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg. 2006;131(5):1080–6.PubMed Shi Y, Denault AY, Couture P, Butnaru A, Carrier M, Tardif JC. Biventricular diastolic filling patterns after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg. 2006;131(5):1080–6.PubMed
48.
Zurück zum Zitat Mehta PK, Wei J, Wenger NK. Ischemic heart disease in women: a focus on risk factors. Trends Cardiovasc Med. 2015;25(2):140–51.PubMed Mehta PK, Wei J, Wenger NK. Ischemic heart disease in women: a focus on risk factors. Trends Cardiovasc Med. 2015;25(2):140–51.PubMed
49.
Zurück zum Zitat Charlson FJ, Moran AE, Freedman G, Norman RE, Stapelberg NJ, Baxter AJ, Vos T, Whiteford HA. The contribution of major depression to the global burden of ischemic heart disease: a comparative risk assessment. BMC Med. 2013;11:250.PubMedPubMedCentral Charlson FJ, Moran AE, Freedman G, Norman RE, Stapelberg NJ, Baxter AJ, Vos T, Whiteford HA. The contribution of major depression to the global burden of ischemic heart disease: a comparative risk assessment. BMC Med. 2013;11:250.PubMedPubMedCentral
50.
Zurück zum Zitat Kivimaki M, Nyberg ST, Batty GD, Fransson EI, Heikkila K, Alfredsson L, Bjorner JB, Borritz M, Burr H, Casini A, et al. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. Lancet. 2012;380(9852):1491–7.PubMedPubMedCentral Kivimaki M, Nyberg ST, Batty GD, Fransson EI, Heikkila K, Alfredsson L, Bjorner JB, Borritz M, Burr H, Casini A, et al. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. Lancet. 2012;380(9852):1491–7.PubMedPubMedCentral
51.
Zurück zum Zitat Ambrose JA, Singh M. Pathophysiology of coronary artery disease leading to acute coronary syndromes. F1000prime rep. 2015;7:08.PubMedPubMedCentral Ambrose JA, Singh M. Pathophysiology of coronary artery disease leading to acute coronary syndromes. F1000prime rep. 2015;7:08.PubMedPubMedCentral
52.
Zurück zum Zitat Arbeus M, Axelsson B, Friberg O, Magnuson A, Bodin L, Hultman J. Milrinone increases flow in coronary artery bypass grafts after cardiopulmonary bypass: a prospective, randomized, double-blind, placebo-controlled study. J Cardiothorac Vasc Anesth. 2009;23(1):48–53.PubMed Arbeus M, Axelsson B, Friberg O, Magnuson A, Bodin L, Hultman J. Milrinone increases flow in coronary artery bypass grafts after cardiopulmonary bypass: a prospective, randomized, double-blind, placebo-controlled study. J Cardiothorac Vasc Anesth. 2009;23(1):48–53.PubMed
53.
Zurück zum Zitat Song JW, Jo YY, Jun NH, Kim HK, Kwak YL. The effect of milrinone on the intraoperative hemodynamics during off-pump coronary bypass surgery in patients with an elevated echocardiographic index of the ventricular filling pressure. Korean J Anesthesiol. 2011;60(3):185–91.PubMedPubMedCentral Song JW, Jo YY, Jun NH, Kim HK, Kwak YL. The effect of milrinone on the intraoperative hemodynamics during off-pump coronary bypass surgery in patients with an elevated echocardiographic index of the ventricular filling pressure. Korean J Anesthesiol. 2011;60(3):185–91.PubMedPubMedCentral
54.
Zurück zum Zitat Yamaguchi A, Tanaka M, Naito K, Kimura C, Kobinata T, Okamura H, Ino T, Adachi H. The efficacy of intravenous milrinone in left ventricular restoration. Ann Thorac Cardiovasc Surg. 2009;15(4):233–8.PubMed Yamaguchi A, Tanaka M, Naito K, Kimura C, Kobinata T, Okamura H, Ino T, Adachi H. The efficacy of intravenous milrinone in left ventricular restoration. Ann Thorac Cardiovasc Surg. 2009;15(4):233–8.PubMed
55.
Zurück zum Zitat Yamaura K, Okamoto H, Akiyoshi K, Irita K, Taniyama T, Takahashi S. Effect of low-dose milrinone on gastric intramucosal pH and systemic inflammation after hypothermic cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2001;15(2):197–203.PubMed Yamaura K, Okamoto H, Akiyoshi K, Irita K, Taniyama T, Takahashi S. Effect of low-dose milrinone on gastric intramucosal pH and systemic inflammation after hypothermic cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2001;15(2):197–203.PubMed
56.
Zurück zum Zitat Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the global burden of disease study 2015. Lancet 2016, 388(10053):1545–1602. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the global burden of disease study 2015. Lancet 2016, 388(10053):1545–1602.
57.
Zurück zum Zitat Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the global burden of disease study 2015. Lancet 2016, 388(10053):1459–1544. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the global burden of disease study 2015. Lancet 2016, 388(10053):1459–1544.
58.
Zurück zum Zitat Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Murray CJ, Naghavi M. Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: the global burden of disease 2010 study. Circulation. 2014;129(14):1483–92.PubMedPubMedCentral Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Murray CJ, Naghavi M. Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: the global burden of disease 2010 study. Circulation. 2014;129(14):1483–92.PubMedPubMedCentral
59.
Zurück zum Zitat Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Flaxman A, Murray CJ, Naghavi M. The global burden of ischemic heart disease in 1990 and 2010: the global burden of disease 2010 study. Circulation. 2014;129(14):1493–501.PubMedPubMedCentral Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Flaxman A, Murray CJ, Naghavi M. The global burden of ischemic heart disease in 1990 and 2010: the global burden of disease 2010 study. Circulation. 2014;129(14):1493–501.PubMedPubMedCentral
60.
Zurück zum Zitat Aguilar-Palacio I, Malo S, Feja C, Lallana M, Leon-Latre M, Casasnovas JA, Rabanaque M, Guallar E. Risk factors control for primary prevention of cardiovascular disease in men: evidence from the Aragon workers health study (AWHS). PLoS One. 2018;13(2):e0193541.PubMedPubMedCentral Aguilar-Palacio I, Malo S, Feja C, Lallana M, Leon-Latre M, Casasnovas JA, Rabanaque M, Guallar E. Risk factors control for primary prevention of cardiovascular disease in men: evidence from the Aragon workers health study (AWHS). PLoS One. 2018;13(2):e0193541.PubMedPubMedCentral
61.
Zurück zum Zitat Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Thorac Cardiovasc Surg. 2015;149(3):e5–23.PubMed Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Thorac Cardiovasc Surg. 2015;149(3):e5–23.PubMed
62.
Zurück zum Zitat Anguita M, Comin J, Almenar L, Crespo M, Delgado J, Gonzalez-Costello J, Hernandez-Madrid A, Manito N, Perez de la Sota E, Segovia J, et al. Comments on the ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. A report of the task force of the clinical practice guidelines Committee of the Spanish Society of cardiology. Rev Esp Cardiol (Engl Ed). 2012;65(10):874–8. Anguita M, Comin J, Almenar L, Crespo M, Delgado J, Gonzalez-Costello J, Hernandez-Madrid A, Manito N, Perez de la Sota E, Segovia J, et al. Comments on the ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. A report of the task force of the clinical practice guidelines Committee of the Spanish Society of cardiology. Rev Esp Cardiol (Engl Ed). 2012;65(10):874–8.
63.
Zurück zum Zitat McGill HC Jr, McMahan CA, Gidding SS. Preventing heart disease in the 21st century: implications of the Pathobiological determinants of atherosclerosis in youth (PDAY) study. Circulation. 2008;117(9):1216–27.PubMed McGill HC Jr, McMahan CA, Gidding SS. Preventing heart disease in the 21st century: implications of the Pathobiological determinants of atherosclerosis in youth (PDAY) study. Circulation. 2008;117(9):1216–27.PubMed
64.
Zurück zum Zitat McNeal CJ, Dajani T, Wilson D, Cassidy-Bushrow AE, Dickerson JB, Ory M. Hypercholesterolemia in youth: opportunities and obstacles to prevent premature atherosclerotic cardiovascular disease. Curr Atheroscler Rep. 2010;12(1):20–8.PubMed McNeal CJ, Dajani T, Wilson D, Cassidy-Bushrow AE, Dickerson JB, Ory M. Hypercholesterolemia in youth: opportunities and obstacles to prevent premature atherosclerotic cardiovascular disease. Curr Atheroscler Rep. 2010;12(1):20–8.PubMed
65.
Zurück zum Zitat Naci H, Ioannidis JP. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ. 2013;347:f5577.PubMedPubMedCentral Naci H, Ioannidis JP. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ. 2013;347:f5577.PubMedPubMedCentral
66.
Zurück zum Zitat Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, Veerman JL, Delwiche K, Iannarone ML, Moyer ML, et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the global burden of disease study 2013. BMJ. 2016;354:i3857.PubMedPubMedCentral Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, Veerman JL, Delwiche K, Iannarone ML, Moyer ML, et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the global burden of disease study 2013. BMJ. 2016;354:i3857.PubMedPubMedCentral
67.
Zurück zum Zitat Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, Berra K, Blair SN, Costa F, Franklin B, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the council on clinical cardiology (subcommittee on exercise, rehabilitation, and prevention) and the council on nutrition, physical activity, and metabolism (subcommittee on physical activity). Circulation. 2003;107(24):3109–16.PubMed Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, Berra K, Blair SN, Costa F, Franklin B, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the council on clinical cardiology (subcommittee on exercise, rehabilitation, and prevention) and the council on nutrition, physical activity, and metabolism (subcommittee on physical activity). Circulation. 2003;107(24):3109–16.PubMed
68.
Zurück zum Zitat Gutierrez J, Ramirez G, Rundek T, Sacco RL. Statin therapy in the prevention of recurrent cardiovascular events: a sex-based meta-analysis. Arch Intern Med. 2012;172(12):909–19.PubMed Gutierrez J, Ramirez G, Rundek T, Sacco RL. Statin therapy in the prevention of recurrent cardiovascular events: a sex-based meta-analysis. Arch Intern Med. 2012;172(12):909–19.PubMed
69.
Zurück zum Zitat Ohman EM. CLINICAL PRACTICE. Chronic stable angina. N Engl J Med. 2016;374(12):1167–76.PubMed Ohman EM. CLINICAL PRACTICE. Chronic stable angina. N Engl J Med. 2016;374(12):1167–76.PubMed
70.
Zurück zum Zitat Sipahi I, Akay MH, Dagdelen S, Blitz A, Alhan C. Coronary artery bypass grafting vs percutaneous coronary intervention and long-term mortality and morbidity in multivessel disease: meta-analysis of randomized clinical trials of the arterial grafting and stenting era. JAMA Intern Med. 2014;174(2):223–30.PubMed Sipahi I, Akay MH, Dagdelen S, Blitz A, Alhan C. Coronary artery bypass grafting vs percutaneous coronary intervention and long-term mortality and morbidity in multivessel disease: meta-analysis of randomized clinical trials of the arterial grafting and stenting era. JAMA Intern Med. 2014;174(2):223–30.PubMed
71.
Zurück zum Zitat Stergiopoulos K, Boden WE, Hartigan P, Mobius-Winkler S, Hambrecht R, Hueb W, Hardison RM, Abbott JD, Brown DL. Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials. JAMA Intern Med. 2014;174(2):232–40.PubMed Stergiopoulos K, Boden WE, Hartigan P, Mobius-Winkler S, Hambrecht R, Hueb W, Hardison RM, Abbott JD, Brown DL. Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials. JAMA Intern Med. 2014;174(2):232–40.PubMed
72.
Zurück zum Zitat Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002;40(7):1366–74.PubMed Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002;40(7):1366–74.PubMed
73.
Zurück zum Zitat Head SJ, da Costa BR, Beumer B, Stefanini GG, Alfonso F, Clemmensen PM, Collet JP, Cremer J, Falk V, Filippatos G, et al. Adverse events while awaiting myocardial revascularization: a systematic review and meta-analysis. Eur J Cardio-Thorac Surg. 2017;52(2):206–17. Head SJ, da Costa BR, Beumer B, Stefanini GG, Alfonso F, Clemmensen PM, Collet JP, Cremer J, Falk V, Filippatos G, et al. Adverse events while awaiting myocardial revascularization: a systematic review and meta-analysis. Eur J Cardio-Thorac Surg. 2017;52(2):206–17.
74.
Zurück zum Zitat Gasz B. The influence of healthcare policy on the outcome parameters of myocardial revascularization procedures as opposed to geographical differences. Eur J Cardio-Thorac Surg. 2018;54(1):196. Gasz B. The influence of healthcare policy on the outcome parameters of myocardial revascularization procedures as opposed to geographical differences. Eur J Cardio-Thorac Surg. 2018;54(1):196.
75.
Zurück zum Zitat Byrne JG, Leacche M. Off-pump CABG surgery “no-touch” technique to reduce adverse neurological outcomes. J Am Coll Cardiol. 2017;69(8):937–8.PubMed Byrne JG, Leacche M. Off-pump CABG surgery “no-touch” technique to reduce adverse neurological outcomes. J Am Coll Cardiol. 2017;69(8):937–8.PubMed
76.
Zurück zum Zitat Karkhanis R, Tam DY, Fremes SE. Management of patients with end-stage renal disease: coronary artery bypass graft surgery versus percutaneous coronary intervention. Curr Opin Cardiol. 2018;33(5):546–50.PubMed Karkhanis R, Tam DY, Fremes SE. Management of patients with end-stage renal disease: coronary artery bypass graft surgery versus percutaneous coronary intervention. Curr Opin Cardiol. 2018;33(5):546–50.PubMed
77.
Zurück zum Zitat Makikallio T, Holm NR, Lindsay M, Spence MS, Erglis A, Menown IB, Trovik T, Eskola M, Romppanen H, Kellerth T, et al. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. Lancet. 2016;388(10061):2743–52.PubMed Makikallio T, Holm NR, Lindsay M, Spence MS, Erglis A, Menown IB, Trovik T, Eskola M, Romppanen H, Kellerth T, et al. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. Lancet. 2016;388(10061):2743–52.PubMed
78.
Zurück zum Zitat Park SJ. Stenting versus bypass surgery for the treatment of left main coronary artery disease. Yonsei Med J. 2009;50(6):739–43.PubMedPubMedCentral Park SJ. Stenting versus bypass surgery for the treatment of left main coronary artery disease. Yonsei Med J. 2009;50(6):739–43.PubMedPubMedCentral
79.
Zurück zum Zitat Ohno K, Kuno A, Murase H, Muratsubaki S, Miki T, Tanno M, Yano T, Ishikawa S, Yamashita T, Miura T. Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal toll-like receptors in rats. Am J Phys Heart Circ Phys. 2017;313(6):H1130–42. Ohno K, Kuno A, Murase H, Muratsubaki S, Miki T, Tanno M, Yano T, Ishikawa S, Yamashita T, Miura T. Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal toll-like receptors in rats. Am J Phys Heart Circ Phys. 2017;313(6):H1130–42.
80.
Zurück zum Zitat Movsesian M, Ahmad F, Hirsch E. Functions of PDE3 Isoforms in Cardiac Muscle. J Cardiovasc Dev Dis. 2018;5:10. Movsesian M, Ahmad F, Hirsch E. Functions of PDE3 Isoforms in Cardiac Muscle. J Cardiovasc Dev Dis. 2018;5:10.
81.
Zurück zum Zitat Madeira M, Caetano F, Almeida I, Fernandes A, Reis L, Costa M, Goncalves L. Inotropes and cardiorenal syndrome in acute heart failure - a retrospective comparative analysis. Rev Portuguesa Cardiol. 2017;36(9):619–25. Madeira M, Caetano F, Almeida I, Fernandes A, Reis L, Costa M, Goncalves L. Inotropes and cardiorenal syndrome in acute heart failure - a retrospective comparative analysis. Rev Portuguesa Cardiol. 2017;36(9):619–25.
82.
Zurück zum Zitat Gao B, Qu Y, Sutherland W, Chui RW, Hoagland K, Vargas HM. Decreased contractility and altered responses to inotropic agents in myocytes from tachypacing-induced heart failure canines. J Pharmacol Toxicol Methods. 2018;93:98–107.PubMed Gao B, Qu Y, Sutherland W, Chui RW, Hoagland K, Vargas HM. Decreased contractility and altered responses to inotropic agents in myocytes from tachypacing-induced heart failure canines. J Pharmacol Toxicol Methods. 2018;93:98–107.PubMed
83.
Zurück zum Zitat Parissis JT, Farmakis D, Nieminen M. Classical inotropes and new cardiac enhancers. Heart Fail Rev. 2007;12(2):149–56.PubMed Parissis JT, Farmakis D, Nieminen M. Classical inotropes and new cardiac enhancers. Heart Fail Rev. 2007;12(2):149–56.PubMed
84.
Zurück zum Zitat Kikura M, Sato S. Effects of preemptive therapy with milrinone or amrinone on perioperative platelet function and haemostasis in patients undergoing coronary bypass grafting. Platelets. 2003;14(5):277–82.PubMed Kikura M, Sato S. Effects of preemptive therapy with milrinone or amrinone on perioperative platelet function and haemostasis in patients undergoing coronary bypass grafting. Platelets. 2003;14(5):277–82.PubMed
85.
Zurück zum Zitat Heringlake M, Wernerus M, Grunefeld J, Klaus S, Heinze H, Bechtel M, Bahlmann L, Poeling J, Schon J. The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting. Crit Care. 2007;11(2):R51.PubMedPubMedCentral Heringlake M, Wernerus M, Grunefeld J, Klaus S, Heinze H, Bechtel M, Bahlmann L, Poeling J, Schon J. The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting. Crit Care. 2007;11(2):R51.PubMedPubMedCentral
86.
Zurück zum Zitat Metra M, Eichhorn E, Abraham WT, Linseman J, Bohm M, Corbalan R, DeMets D, De Marco T, Elkayam U, Gerber M, et al. Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials. Eur Heart J. 2009;30(24):3015–26.PubMedPubMedCentral Metra M, Eichhorn E, Abraham WT, Linseman J, Bohm M, Corbalan R, DeMets D, De Marco T, Elkayam U, Gerber M, et al. Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials. Eur Heart J. 2009;30(24):3015–26.PubMedPubMedCentral
87.
Zurück zum Zitat Bayram M, De Luca L, Massie MB, Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005;96(6A):47G–58G.PubMed Bayram M, De Luca L, Massie MB, Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005;96(6A):47G–58G.PubMed
88.
Zurück zum Zitat Mebazaa A, Parissis J, Porcher R, Gayat E, Nikolaou M, Boas FV, Delgado JF, Follath F. Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods. Intensive Care Med. 2011;37(2):290–301.PubMed Mebazaa A, Parissis J, Porcher R, Gayat E, Nikolaou M, Boas FV, Delgado JF, Follath F. Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods. Intensive Care Med. 2011;37(2):290–301.PubMed
89.
Zurück zum Zitat Lee J, Kim WH, Ryu HG, Lee HC, Chung EJ, Yang SM, Jung CW. Stroke volume variation-guided versus central venous pressure-guided low central venous pressure with Milrinone during living donor hepatectomy: a randomized double-blinded clinical trial. Anesth Analg. 2017;125(2):423–30.PubMed Lee J, Kim WH, Ryu HG, Lee HC, Chung EJ, Yang SM, Jung CW. Stroke volume variation-guided versus central venous pressure-guided low central venous pressure with Milrinone during living donor hepatectomy: a randomized double-blinded clinical trial. Anesth Analg. 2017;125(2):423–30.PubMed
90.
Zurück zum Zitat Movsesian M, Stehlik J, Vandeput F, Bristow MR. Phosphodiesterase inhibition in heart failure. Heart Fail Rev. 2009;14(4):255–63.PubMed Movsesian M, Stehlik J, Vandeput F, Bristow MR. Phosphodiesterase inhibition in heart failure. Heart Fail Rev. 2009;14(4):255–63.PubMed
91.
Zurück zum Zitat Belletti A, Castro ML, Silvetti S, Greco T, Biondi-Zoccai G, Pasin L, Zangrillo A, Landoni G. The effect of inotropes and vasopressors on mortality: a meta-analysis of randomized clinical trials. Br J Anaesth. 2015;115(5):656–75.PubMed Belletti A, Castro ML, Silvetti S, Greco T, Biondi-Zoccai G, Pasin L, Zangrillo A, Landoni G. The effect of inotropes and vasopressors on mortality: a meta-analysis of randomized clinical trials. Br J Anaesth. 2015;115(5):656–75.PubMed
92.
Zurück zum Zitat Koster G, Bekema HJ, Wetterslev J, Gluud C, Keus F, van der Horst IC. Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med. 2016;42(9):1322–35.PubMedPubMedCentral Koster G, Bekema HJ, Wetterslev J, Gluud C, Keus F, van der Horst IC. Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med. 2016;42(9):1322–35.PubMedPubMedCentral
Metadaten
Titel
The effect of milrinone on mortality in adult patients who underwent CABG surgery: a systematic review of randomized clinical trials with a meta-analysis and trial sequential analysis
verfasst von
Yu-shan Ren
Lan-fang Li
Tao Peng
Yu-jun Tan
Ying Sun
Guo-liang Cheng
Gui-min Zhang
Jie Li
Publikationsdatum
01.12.2020
Verlag
BioMed Central
Erschienen in
BMC Cardiovascular Disorders / Ausgabe 1/2020
Elektronische ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-020-01598-8

Weitere Artikel der Ausgabe 1/2020

BMC Cardiovascular Disorders 1/2020 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.