Comparison of Outcomes in Patients With Insulin-Dependent Versus Non-Insulin Dependent Diabetes Mellitus Receiving Drug-Eluting Stents (from the First Phase of the Prospective Multicenter German DES.DE Registry)

doi:10.1016/j.amjcard.2010.06.042

The American Journal of Cardiology

Volume 106, Issue 9, 1 November 2010, Pages 1201-1207

https://doi.org/10.1016/j.amjcard.2010.06.042 Get rights and content

Drug-eluting stents have been effective in randomized controlled trials, but their safety and efficacy in patients with insulin-dependent diabetes has not been well studied. Baseline clinical and angiographic characteristics and in-hospital and follow-up events were recorded for enrolled patients. From October 2005 and October 2006, 581 patients with insulin-dependent diabetes and 1,078 with non-insulin-dependent diabetes treated with sirolimus- and paclitaxel-eluting stents were enrolled at 98 sites. The composite of death, myocardial infarction, and stroke, defined as major adverse cardiac and cerebrovascular events, as well as target vessel revascularization was used as the primary end point. Multiple logistic regression analysis was used to adjust for confounding parameters. Baseline clinical characteristics were more severe in patients with insulin-dependent diabetes, whereas descriptive characteristics were not unique. At 1-year follow-up, the comparison between the 2 groups revealed significantly higher rates of overall death (7.4% vs 4.6%, p <0.05), target vessel revascularization (15.1% vs 10.4%, p <0.05), and overall stent thrombosis (6.5% vs 4.1%, p <0.05) for insulin-dependent patients, while rates of major adverse cardiac and cerebrovascular events were not significantly different (12.8% vs 9.9%, p = 0.09). These results persisted even after risk adjustment for heterogenous baseline characteristics of the 2 groups. In conclusion, the data generated from the German Drug-Eluting Stent (DES.DE) registry revealed that even with drug-eluting stents, the annual risk for death, target vessel revascularization, and thrombotic events remains higher in patients with insulin-dependent diabetes compared to those with non-insulin-dependent diabetes.

Section snippets

Methods

The large, prospective, multicenter German Drug-Eluting Stent (DES.DE) registry design has been previously published.⁴ Briefly, the registry was initiated in October 2005 as an observational cohort study by Deutsche Gesellschaft für Kardiologie (the German Cardiac Society), Bundesverband Niedergelassener Kardiologen (the German Society of Cardiologists in Private Practice), and Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (Working Group of Hospital Cardiologists) to evaluate the

Results

From October 2005 to October 2006, 1,659 patients with diabetes treated with either paclitaxel-eluting stents or sirolimus-eluting stents were enrolled at 98 sites. The analysis was based on 962 patients (58.0%) receiving only paclitaxel-eluting stents, 668 (40.3%) receiving only sirolimus-eluting stents, and 29 (1.7%) who received a combination of paclitaxel-eluting stents and sirolimus-eluting stents. Among these patients, 581 (35.0%) had IDDM and 1,078 had NIDDM, with 849 (78.7%) receiving

Discussion

Diabetes mellitus is an important risk factor for cardiovascular disease progression. Coronary artery lesions in patients with diabetes are more often diffuse, occurring in multiple vessels with small luminal diameters and in segments adjacent to obstructive occlusions.¹³ A Finnish long-term follow-up study¹⁴ and the Nurses' Health Study¹⁵ revealed markedly larger numbers of fatal coronary events in patients with type 2 diabetes than in patients without diabetes after previous myocardial

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Short- and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: A systematic review and meta-analysis
2022, Indian Heart Journal
This study aims to assess differences in severity of short-term (<1 year) and long-term (≥1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients.
A systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulin-treated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I² statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias.
A total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR = 1.75 [1.24,2.47]; p = 0.002), MI (RR = 1.81[1.14,2.87]; p = 0.01], stent thrombosis (RR = 1.63[1.13, 2.35]; p = 0.009) and target lesion revascularization (TLR) (RR = 1.29[1.02,1.63]; p = 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR = 1.55 [1.22, 1.97]; p = 0.0003), MI (RR = 1.63 [1.35, 1.97]; p=<0.00001), MACE (R = 1.47 [1.31, 1.65]; p=<0.00001), stent thrombosis (RR = 1.54 [1.19,1.99]; p = 0.001), TLR (RR = 1.40 [1.18, 1.66]; p = 0.0001), target vessel revascularization (TVR) (RR = 1.35 [1.11, 1.64]; p = 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients.
Despite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.
Comparison of Long-Term Outcomes After Percutaneous Coronary Intervention in Patients With Insulin-Treated Versus Non-Insulin Treated Diabetes Mellitus
2021, American Journal of Cardiology
There are conflicting data on whether patients with insulin-treated diabetes mellitus (ITDM) have poorer outcomes compared with non-insulin treated diabetic (non-ITDM) patients following percutaneous coronary intervention (PCI). We therefore compared clinical outcomes following PCI in ITDM versus non-ITDM patients. We prospectively collected data on 4,579 patients with diabetes underwent PCI between 2005 and 2014 in a large multicenter registry and dichotomized them as having ITDM (n = 1,111) or non-ITDM (n = 3,468). The non-ITDM group was further divided into diet control only (diet-DM; n = 786) and those taking oral hypoglycemic agents (OHG-DM; n = 2,639), and clinical outcomes were compared with ITDM patients. Median follow-up for long-term mortality was 4.2 years (IQR 2.0 to 6.6 years). ITDM patients were more likely to be female, obese, and have severe renal impairment (all p <0.001). Procedural characteristics were similar other than a greater use of drug-eluting stents in ITDM patients. On multivariable analysis, ITDM was an independent predictor of 12-month major adverse cardiovascular and cerebrovascular events (MACCE; OR 1.26, 95% CI 1.02 to1.55, p = 0.03). Dividing the non-ITDM group further by treatment, a progressively higher rate of 12-month MACCE across the 3 groups was observed (13.5% vs 17.9% vs 21.8%; p <0.001). Long-term mortality was similar in the diet-DM and OHG-DM groups, but significantly higher in the ITDM group on Kaplan-Meier analysis (log-rank p <0.001). In conclusion, there is a clear gradient of adverse outcomes with escalation of therapy from diet control to OHGs to insulin.
Impact of Insulin-Treated and Noninsulin-Treated Diabetes Mellitus in All-Comer Patients Undergoing Percutaneous Coronary Interventions With Polymer-Free Biolimus-Eluting Stent (from the RUDI-FREE Registry)
2019, American Journal of Cardiology
Patients with diabetes mellitus (DM) have worse outcomes after percutaneous coronary intervention (PCI). Recent evidences suggest a differential impact of insulin-treated and noninsulin-treated DM on prognosis. We evaluated the clinical outcome of diabetic patients after PCI with polymer-free biolimus-eluting stent from the RUDI-FREE Registry, investigating a possible different prognostic impact of insulin-treated and noninsulin-treated DM. A total of 1,104 consecutive patients who underwent PCI with polymer-free biolimus-eluting stent, enrolled in the RUDI-FREE observational, multicenter, single-arm registry, were stratified by diabetic status; diabetic population was further divided on the basis of insulin treatment. Primary end points of the study were target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, target lesion revascularization) and major adverse cardiac and cerebrovascular events (composite of cardiac death, stroke, and myocardial infarction). Multiple ischemic adverse events were also single-handedly considered as secondary end points. At 1 year, TLF was significantly higher in the diabetic cohort, as compared with nondiabetic patients (6.0% vs 3.1%, p 0.022). None of the end points resulted significantly different between nondiabetics and noninsulin-treated diabetic patients. Divergently, compared with nondiabetic, insulin-treated diabetic patients faced significant higher rates of TLF (10.8% vs 3.1%, p 0.003), major adverse cardiac and cerebrovascular events (10.8% vs 3.4%, p 0.004), and of most of the analyzed adverse events. In conclusion, patients with DM had a higher risk of TLF compared with nondiabetics; nonetheless, the worse outcome of the diabetic population seems to be driven by the insulin-treated diabetic subpopulation. This finding suggests a different risk profile of insulin-treated and noninsulin-treated diabetic patients in the modern era of PCI.
MicroRNA-24 attenuates vascular remodeling in diabetic rats through PI3K/Akt signaling pathway
2019, Nutrition, Metabolism and Cardiovascular Diseases
Citation Excerpt :
However, existing diabetes drugs can only reduce vascular complications to a certain extent by strictly controlling blood glucose [37]. Even with the application of drug eluting stents (DES), the adjusted risk of restenosis was higher in patients with DM than in patients without DM [3,5,38]. Thus, optimal therapies against neointimal hyperplasia in diabetics are limited.
The vascular remodeling plays a crucial role in pathogenesis of diabetic cardiovascular complications. In this study, we intended to explore the effects and potential mechanisms of microRNA-24 (miR-24) on vascular remodeling under diabetic conditions.
MiR-24 recombinant adenovirus (Ad-miR-24-GFP) was used to induce miR-24 overexpression either in carotid arteries or high glucose (HG)-induced vascular smooth muscle cells (VSMCs). Cell proliferation was analyzed using CCK-8 method. Cell migration was examined using wound-healing and transwell assay. mRNA and protein expressions of critical factors were, respectively, measured by real-time PCR and western blot as follows: qRT-PCR for the levels of miR-24, PIK3R1; western blot for the protein levels of PI3K (p85α), Akt, p-Akt, mTOR, p-mTOR, 4E-BP1, p-4E-BP1, p70s6k, p-p70s6k, MMP 2, MMP 9, collagen Ⅰ, as well as collagen Ⅲ. Carotid arteries in diabetic rats suffered balloon injury were harvested and examined by HE, immunohistochemical and Masson trichrome staining.
The expression of miR-24 was decreased in HG-stimulated VSMCs and balloon-injured carotid arteries of diabetic rats, accompanied by increased mRNA expression of PIK3R1. The up-regulation of miR-24 suppressed VSMCs proliferation, migration, collagen deposition not only induced by HG in vitro, but also in balloon-injured diabetic rats, which were related to inactivation of PI3K/Akt signaling pathway.
The up-regulation of miR-24 significantly attenuated vascular remodeling both in balloon-injured diabetic rats and HG-stimulated VSMCs via suppression of proliferation, migration and collagen deposition by acting on PIK3R1 gene that modulated the PI3K/Akt/mTOR axes.
Meta-Analysis of Impact of Diabetes Mellitus on Outcomes After Transcatheter Aortic Valve Implantation
2017, American Journal of Cardiology
To date, the impact of diabetes mellitus (DM) on prognosis after transcatheter aortic valve implantation (TAVI) is still contradictory and thus merits further investigation. The purpose of this meta-analysis was to evaluate the impact of DM on outcomes after TAVI. A systematic search of the PubMed database was performed. Primary end points were 30-day and 1-year all-cause mortality after TAVI. Risk ratios (RRs) and 95% CIs were calculated using the random-effect or fixed-effect model, depending on heterogeneity between studies, and p values <0.05 was considered significant. A total of 16 studies involving 13,253 patients were included in our meta-analysis. There was no significant difference between the groups with DM and without DM regarding 30-day (RR 1.07, 95% CI 0.90 to 1.27, p = 0.45) or 1-year (RR 1.04, 95% CI 0.94 to 1.15, p = 0.42) all-cause mortality. The risks of 30-day complications, including myocardial infarction, stroke, major vascular complications, major bleeding, and acute kidney injury, were similar between patients with and without DM. In conclusion, DM neither affected short- or mid-term all-cause mortality nor short-term complications after TAVI.
Efficacy and Safety of the Absorb Everolimus-Eluting Bioresorbable Scaffold for Treatment of Patients With Diabetes Mellitus: Results of the Absorb Diabetic Substudy
2017, JACC: Cardiovascular Interventions
The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus.
Randomized, controlled trials have demonstrated comparable clinical outcomes following percutaneous coronary intervention with either Absorb BVS or metallic Xience everolimus-eluting stent. However, these trials lack power required to provide reliable treatment effect estimates in this high-risk population.
In a pre-specified, powered analysis, patients with diabetes who received ≥1 Absorb were pooled from the ABSORB II, III, and JAPAN randomized trials and from the single arm ABSORB EXTEND registry. The study composite primary endpoint was target lesion failure (TLF) at 1 year following Absorb BVS compared with a performance goal of 12.7%.
Among 754 diabetic patients included in analysis (27.3% insulin treated), the 1-year TLF rate was 8.3% (upper 1-sided 95% confidence limit: 10.1%; p = 0.0001 vs. performance goal). Scaffold thrombosis (definite or probable) was observed in 2.3% of patients. Multivariable regression identified older age, insulin treatment, and smaller pre-procedure reference vessel diameter as significant independent predictors of 1-year TLF.
The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus.

View all citing articles on Scopus

^†: A list of investigators of the German Drug-Eluting Stent (DES.DE) registry appears in the Appendix.

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Coronary artery diseaseComparison of Outcomes in Patients With Insulin-Dependent Versus Non-Insulin Dependent Diabetes Mellitus Receiving Drug-Eluting Stents (from the First Phase of the Prospective Multicenter German DES.DE Registry)†

Section snippets

Methods

Results

Discussion

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

JACC Cardiovasc Interv

J Am Coll Cardiol

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary

Eur Heart J

Guidelines for percutaneous coronary interventions: the Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology

Eur Heart J

2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Circulation

A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents

N Engl J Med

Coronary artery disease
Comparison of Outcomes in Patients With Insulin-Dependent Versus Non-Insulin Dependent Diabetes Mellitus Receiving Drug-Eluting Stents (from the First Phase of the Prospective Multicenter German DES.DE Registry)^†