Clinical features, use of evidence-based therapies, and cardiovascular outcomes among patients with chronic kidney disease following non-ST-elevation acute coronary syndrome

Abstract

Background: Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular events following acute coronary syndrome (ACS). The underlying pathobiology and optimal treatments for this population continue to be evaluated.

Hypothesis: Patients with CKD will receive fewer evidence-based therapies and experience high rates of adverse cardiovascular events in both the short- and long term.

Methods: The MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction 36) trial randomized non-ST-elevation ACS patients to ranolazine or placebo, with no exclusion for renal dysfunction (except dialysis). We conducted a prespecified analysis among 6543 patients based on the degree of CKD.

Results: Patients with worse renal function were older with more comorbidities (P < 0.0001 for each). They were less likely to receive evidence-based cardiovascular medicines (P < 0.04 for each). Rates of an early invasive management strategy varied based on renal function; however, among patients with the highest TIMI risk scores, the rates of an early invasive management strategy were similar regardless of glomerular filtration rate (GFR) (Pinteraction = 0.005). Lower GFR was associated with increased rates of cardiovascular disease or myocardial infarction in the short and long term, even after adjustment (GFR <30 vs ≥90 mL/min/1.73 m(2) ; hazard ratio [HR]: 3.24 [95% confidence interval {CI}: 1.26-8.38] through 7 days and HR: 2.12 [95% CI: 1.33-3.39] through 1 year). The effect of ranolazine vs placebo on clinical outcomes was similar among those with and without CKD (Pinteraction = not significant).

Conclusions: Following ACS, patients with renal dysfunction had more cardiovascular risk factors but were less likely to receive evidence-based medical therapies. A strong graded, independent relationship between the degree of CKD and poor clinical outcomes was observed over time. Continued efforts to optimize ACS treatment strategies in patients with CKD are warranted.

Trial registration: ClinicalTrials.gov NCT00099788.

© 2014 Wiley Periodicals, Inc.

Figures

Figure 1

Proportion of patients who underwent an early invasive management strategy based on glomerular filtration rate (GFR) across Thrombolysis in Myocardial Infarction (TIMI) risk score categories. Abbreviations: OR, odds ratio.

Figure 2

Kaplan‐Meier event rates at 1 year for cardiovascular death (left panel) and myocardial infarction (right panel) across glomerular filtration rate (GFR) categories. P values are generated from models adjusted for baseline variables (age, sex, weight, diabetes, hypertension, smoking, prior myocardial infarction/revascularization/heart failure), ST depression on presentation, and treatments including intent for early invasive therapy and medications in hospital and/or at discharge.

Figure 3

Risk of cardiovascular death or myocardial infarction at 1 year across glomerular filtration rate (GFR) categories adjusted for baseline variables (age, sex, weight, diabetes, hypertension, smoking, prior myocardial infarction (MI)/revascularization/heart failure), ST depression on presentation, and treatments including intent for early invasive therapy and medications in hospital and/or discharge. Abbreviations: CI, confidence interval; HR, hazard ratio.