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Perindopril Has Synergistic Effect With Calcium Channel Blockers inPrevention of Cardiac Events and Death in Patients With CoronaryArtery Disease: Presented at ESC
By Chris Berrie

MUNICH, Germany -- September 5, 2008 -- Addition of theangiotensin-converting enzyme (ACE) inhibitor perindopril tocalcium channel blocker (CCB) therapy shows a clinical interactionfor reduction of total mortality and major coronary events inpatients with stable coronary artery disease (CAD), according toresults of a post hoc analysis of a randomised, double-blind,placebo-controlled study.

Michel Bertrand, MD, Lille Heart Institute and University of Lille,Lille, France, presented the study findings here at the EuropeanSociety of Cardiology 2008 Congress (ESC) on behalf of the EuropeanTrial on the Reduction of Cardiac Events With Perindopril in StableCoronary Artery Disease (EUROPA).

The aim of the study was to investigate potential synergisticeffects between perindopril and CCBs through an analysis of theEUROPA trial data, Dr. Bertrand said in his presentation onSeptember 2.

The EUROPA trial involved randomisation of 6,108 patients withstable CAD to placebo and 6,110 to perindopril 8 mg/day. Withineach treatment arm, patients either did or did not take a CCB.

With this study design, 1,100 patients received placebo plus CCBand 1,022 received perindopril plus CCB. These patients were a meanof 61.8 and 61.4 years old, respectively, and men made up 84.2% and82.4% of the groups, respectively. Demographic and medication data,as well as CAD and medical histories, were well balanced acrossthese 2 groups.

For the primary endpoint, combined cardiovascular death, nonfatalmyocardial infarction (MI), and resuscitated cardiac arrest reacheda significant 35% reduction in relative risk for perindopril plusCCB versus CCB alone (hazard ratio [HR], 0.645; P = .0147).

For the synergy analysis, Dr. Bertrand said, "Synergy wasconsidered if the hazard ratio of perindopril plus a calciumchannel blocker was lower than the hazard ratio of perindoprilalone multiplied by the hazard ratio of the calcium channel blockeralone, a traditional method for statistics."

Once the data were fully adjusted for a number of covariants, forthe primary endpoint, the HR for the combined treatment was lowerthan that of the product of the 2 treatments alone (0.50 vs 0.64,respectively).

Similarly, the same effect was seen for the HRs of each secondaryendpoint: total mortality (0.31 vs 0.52, respectively),cardiovascular mortality (0.29 vs 0.36), fatal and nonfatal MI(0.68 vs 0.75), and hospitalisation for heart failure (0.14 vs0.18).

"These data show that possibly there is a synergistic effectof the perindopril and calcium channel blockers on theseendpoints," Dr. Bertrand added.

He noted that the types and doses of the CCBs remain unknown,although he speculated that "the absence of differences inheart rate between the subgroups taking and not taking a CCBsuggests that the CCBs were possibly mainly dihydropyridines."

"This clinical interaction between perindopril and CCBs thatsuggests synergistic effects of course merits furtherinvestigation," he added.

Funding for this study was provided by Servier.

[Presentation title: Synergistic Effect of Perindopril and CalciumChannel Blockers in Prevention of Cardiac Events and Death inCoronary Artery Disease Patients -- Analysis From the EUROPA Study.Abstract 3267]