Management quality indicators and in-hospital mortality among acute coronary syndrome patients admitted to tertiary hospitals in Ethiopia: prospective observational study

A prospective observational study was conducted at two tertiary hospitals in Ethiopia including Jimma University Medical Center (JUMC) and Saint Peter’s Specialized Hospital (SPSH). JUMC serves as a referral center for the southwestern part of the country (over 15,000,000 catchment population). JUMC provides general internal medicine, cardiology, and other specialty services. SPSH is in Addis Ababa and it is one of a few public hospitals which provide cardiac catheterization laboratories in Ethiopia. The study was carried out from March 15 to November 15, 2018.

All consecutive ACS patients admitted to JUMC and SPSH fulfilling the inclusion criteria were included. Patients were included if they fulfilled the following inclusion criteria: (I) age ≥ 18 years; (II) willing to provide written or oral informed consent; and (III) confirmed diagnosis of ACS based on the Third Universal Definition of Myocardial Infarction [16]. Patients who died before assessment, readmitted patients, change to the initial ACS diagnoses, and patients with non-type I myocardial infraction (secondary to non-ACS etiology) were excluded from the study. In this study, patients were categorized based on ACS subtype into ST-elevation myocardial infarction (STEMI) or non-ST-elevation acute coronary syndromes [NSTE-ACS: includes unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI)] [17, 18].

Using a pre-tested structured questioner, two trained nurses and two medical interns collected clinical data by interviewing hospitalized patients and extracting relevant data from patient’s medical records. The data collection tool includes sociodemographic characteristics, key diagnostics investigations (electrocardiography, cardiac biomarkers, echocardiography, and angiography), management (guideline-directed medications within the first 24 h of hospital admission and at discharge), and in-hospital clinical outcomes [in-hospital mortality and non-fatal major adverse cardiovascular events (MACE)].

Guideline-directed in-hospital medications were defined as the initiation of dual antiplatelet (Aspirin + one P2Y₁₂ inhibitor), beta blocker, and angiotensin converting enzyme (ACE) inhibitor within 24 h of hospitalization. Guideline-directed discharge medications were defined as receiving dual antiplatelet therapy (aspirin + one P2Y12 inhibitor), beta-blockers, statin, and ACE inhibitor at discharge. Guideline-directed medications were evaluated as quality of care indicators based on the international guideline for the management of STEMI or NSTE-ACS adopted at respective hospitals [17, 18].

The primary outcome of the study was in-hospital mortality which was ascertained from treating physician death summary note. The secondary endpoint was new onset non-fatal MACE defined as a composite of heart failure, stroke, re-infarction, cardiogenic shock, and major bleeding during a hospital stay. Definition for various components of MACE was available in the supplementary material (Clinical Check-list). All clinical endpoints were recorded by following patients on daily basis from admission to discharge or death.

The study protocol was approved by the Institutional Review Board (IRB) of Jimma University, Institute of Health with a reference number of IHRPGD/193/18. Permission was obtained from responsible bodies of respective hospitals before interviewing patients and extracting data from active patient’s case records. Written and verbal informed consent was obtained from all study participants.

The collected data were checked for completeness, clarity, and accuracy. Data was entered into Epidata version 4.2 and analyzed using statistical package for social science (SPSS) version 23 (IBM, Armonk, NY, USA). Patient characteristics, management, and clinical outcomes were summarized according to ACS subtypes. Continuous variables were presented as mean ± standard deviation or median (interquartile range), and categorical variables are presented as frequency (%). In-hospital ACS mortality rate was compared using Kaplan-Meier and log rank test. P-value < 0.25 was considered as a cut-off point to select variables on binary regression for multivariable Cox regression to determine independent predictors of time to ACS mortality. Two-tailed p -value < 0.05 was considered statistically significant.

The mean age of the study participants was 55.8 ± 11.9 years and 62.4% were males. About three -fourths (75.7%) were urban or semi-urban residents while more than half of the patients had no formal education. Only 9.4% of the study participants were transported to the hospital by ambulance. The median (IQR) time from symptom onset to first medical contact was 26 (10–43) hours without significant difference (Table 1).

The majority of the patients (79.6%) received an ECG within the first 24 h of hospital arrival and all patients received an ECG at some point during their hospital stay. Cardiac biomarkers were measured for all patients during hospitalization and 72.4% had elevated troponin I level. Diagnostic angiography was available at SPSH and it was performed for 43.6% of patients. Transthoracic Doppler echocardiography was done for 96.1 and 38.7% of the patients had reduced left ventricular ejection fraction (LVEF) less than 40% (Table 2).

Dual antiplatelet therapy (aspirin + clopidogrel) was administered for 73% of the patients during the first 24 h of hospital admission. The use of other guideline-directed medications includes statin (74.6%), beta-blockers (67.2%), any heparin (61.3), and ACEI/ARB (61.3) within the first 24 h of hospital admission. Patients presented with STEMI were more likely to receive evidence-based medication within the first 24 h of hospitalization compared to those presented with NSTE-ACS (Table 2).

None of the study participants received thrombolytic medications during hospitalization due to the unavailability of the medications. Although 43.6% of the participant undergone diagnostic cardiac catheterization, only 13 (7.2%) of the patients received percutaneous coronary interventions (PCI) during hospitalization.

The overall all in-hospital mortality rate was 20.4% with significant difference between STEMI (26%) and NSTE-ACS (11.4%) [p = 0.017]. The rate of non-fatal MACE defined as cardiogenic shock, stroke, re-infarction, and major bleeding during hospitalization was 25% (STEMI 28% and NSTEMI 20%). Cardiogenic shock was statistically significant among patients presented with STEMI compared to NSTE-ACS patients (p = 0.043). There was no statistically significant difference in other non-fatal MACE among ACS subtypes. Other common complications recorded during hospitalization were acute kidney injury (12.2%), hospital acquired infections (8.8%) and atrial fibrillations (7.2%) (Table 2).

Focusing on guideline-directed discharge medications, we have evaluated prescriptions of key medications on discharge. Discharge dual antiplatelet therapy was 76% (97% for aspirin alone). Statin prescription at discharge was high (96%), followed by beta-blockers (83%) and ACEI/ARB (76%). Discharge prescriptions of aspirin and clopidogrel were more common among STEMI patients compared to NSTEM-ACS patients with statistical significance (p = 0.020 and p = 0.007), respectively (Table 3).

On multivariable Cox-regression analysis, rural residence, symptom onset to FMC > 12 h, and Cardiogenic shock complication were independent predicators of time to in-hospital death among ACS patients. The in-hospital mortality rate was 3.64 times higher in ACS patients from rural areas compared to those from urban areas [Adjusted hazard ratio (AHR): 3.64, 95% CI: 1.81–7.29). Similarly, the rate of in-hospital mortality in patients presented to the hospitals after 12 h of symptom onset was 4.23 times more than patients presented to hospital within 12 h of symptom onset (AHR: 4.23, 95% CI: 1.28–13.81). In addition, the risk of in-hospital mortality in patients who develop cardiogenic shock was 7.20 times more than those patients without cardiogenic shock (AHR: 7.20, 95% CI: 3.55–14.55). (Table 4). Survival probability curve were generated from Kaplan Meier in-hospital death for independent predictors and compared by Log rank (Fig. 1).

Through this observational study, we have identified areas that need improvement to optimize the process of care and outcome among ACS patients. We observed a prolonged delay between symptom onset and presentation to hospitals for emergency care. This finding highlights the importance of creating awareness about ACS symptoms for general populations and community health workers since the prehospital delay was an independent predictor of in-hospital death in the present study. All-cause in-hospital mortality and non-fatal MACE rates in the present study were unacceptably high, stressing the importance of guideline-directed medical therapy and early reperfusion therapy. The use of guideline-directed medications such as dual antiplatelet, bet-blockers, and ACEIs should be prioritized during the acute phase (the first 24 h) since it has an impact on patient prognosis. In addition, increasing the number of interventional cardiologist and PCI cable center in available tertiary care hospitals as well as linking them with general hospitals and emergency medical service might improve outcomes of patients with ACS.

As a strength, the study was prospectively described relevant management protocol, in-hospital outcomes and independent predictors of in-hospital mortality among ACS patients. This study highlighted the process of care as quality indicators and identified area needs improvement to reduce mortality rate and complications among ACS patients in Ethiopia. However, the study has several limitations. First, this study was conducted on a small sample size (181 participants) due to erratic patient follow to selected hospitals. The calculated sample size was 190 based on the study conducted by A. Giday et al. in Ethiopia which reported an in-hospital mortality rate of 14.4% [37]. Second, the data represent patients survived the acute phase because ACS patients who died prehospital and shortly after hospital arrival were excluded. Third, we did not capture a key aspect of quality measures such as door-to-balloon/needle since only a minority of ACS patients received reperfusion therapy. Finally, we did not record economic cost, patient quality of life and post discharge medication adherence and outcomes which are also important performance measures.