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CLINICAL RESEARCH: HEART FAILURE

The Cardioprotective Effects of the Angiotensin-Converting Enzyme Inhibitor Perindopril in Patients With Stable Coronary Artery Disease Are Not Modified by Mild to Moderate Renal Insufficiency

Insights From the EUROPA Trial

Jasper J. Brugts, MD, MSc^_*,1, Eric Boersma, PhD, MSc^_*, Michel Chonchol, MD, Jaap W. Deckers, MD, PhD^_*,2, Michel Bertrand, MD^,2, Willem J. Remme, MD, PhD^,2, Roberto Ferrari, MD, PhD^||,2, Kim Fox, MD^¶,2, Maarten L. Simoons, MD, PhD^_*,2,_* on behalf of the EUROPA Investigators

^_* Department of Cardiology, Thoraxcenter Erasmus Medical Center, Rotterdam, the Netherlands
Department of Renal Disease and Hypertension, University of Colorado, Denver, Colorado
Lille Heart Institute, Lille, France
Sticares Cardiovascular Research Foundation, Rotterdam, the Netherlands
^|| Azienda Ospedalier and University di Ferrara, Ferrara, Italy
^¶ Royal Brompton and National Heart Hospital, London, United Kingdom.

Manuscript received March 12, 2007; revised manuscript received July 6, 2007, accepted August 8, 2007.

^_* Reprint requests and correspondence: Prof. Dr. Maarten L. Simoons, Chief Department of Cardiology, Erasmus MC, Thoraxcenter ‘s Gravendijkwal 230, 3015CE Rotterdam, the Netherlands. (Email: m.simoons{at}erasmusmc.nl).

Objectives: This study sought to examine whether the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitor therapy by perindopril are modified by renal function in patients with stable coronary artery disease.

Background: A recent study reported that an impaired renal function identified a subgroup of patients with stable coronary artery disease more likely to benefit from ACE inhibition therapy. In light of the growing interest in tailored therapy for targeting medications to specific subgroups, remarks on the consistency of the treatment effect by ACE inhibitors are highly important.

Methods: The present study involved 12,056 patients with stable coronary artery disease without heart failure randomized to perindopril or placebo. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease equation. Cox regression analysis was used to estimate multivariable-adjusted hazard ratios.

Results: The mean eGFR was 76.2 (±18.1) ml/min/1.73 m². During follow-up, the primary end point (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) occurred in 454 of 5,761 patients (7.9%) with eGFR 75 and in 631 of 6,295 patients (10.0%) with eGFR <75. Treatment benefits of perindopril were apparent in both patient groups either with eGFR 75 (hazard ratio 0.77; 95% confidence interval 0.64 to 0.93) or eGFR <75 (hazard ratio 0.84; 95% confidence interval 0.72 to 0.98). We observed no significant interaction between renal function and treatment benefit (p = 0.47). Using different cutoff points of eGFR at the level of 60 or 90 resulted in similar trends.

Conclusions: The treatment benefit of perindopril is consistent and not modified by mild to moderate renal insufficiency.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CAD = coronary artery disease   CI = confidence interval   eGFR = estimated glomerular filtration rate   HR = hazard ratio   MI = myocardial infarction