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.
OBJECTIVE
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 > or =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 > or =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.
Department of Cardiology, Thoraxcenter Erasmus Medical Center, Rotterdam, The Netherlands.
Jasper J
JJ
Brugts
Eric
E
Boersma
Michel
M
Chonchol
Jaap W
JW
Deckers
Michel
M
Bertrand
Willem J
WJ
Remme
Roberto
R
Ferrari
Kim
K
Fox
Maarten L
ML
Simoons
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000494:pharmacology / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000150:complications*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril