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Study Results Reveal Potential Genetic Profiling for Prescribing ACE Inhibitors

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A presentation at a meeting of the European Society of Cardiology last month suggested that a genetic profiling model may help predict which cardiac patients will benefit from treatment with ACE inhibitors.

Although the study results require further validation, "if confirmed in subsequent studies, our findings open the route to individualize therapy by pharmacogenetic profiling," study authors said in a statement discussing their analysis.

Researcher Jasper Brugts of the Erasmus University Medical Center in Rotterdam led the randomized, placebo-controlled trial, involving 9,000 patients who are part of the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, or EUROPA. Researchers analyzed 12 candidate genes, determined to be "within the pharmacodynamic pathway of ACE inhibitors, using 52 haplotype-tagging SNPs," Brugts explained in a statement announcing the results of the study.

The primary outcome of the study was a reduction in cardiovascular mortality, non-fatal myocardial infarction, and resuscitated cardiac arrest over a four-year follow-up period. Researchers identified three SNPs, located in the angiotensin-II type I receptor genes and bradykinin type I receptor genes, which were significantly associated with the treatment benefit of perindopril after adjusting for confounding factors and correcting for multiple testing.

"A pharmacogenetic score, combining these three SNPs, demonstrated a stepwise reduction of risk in the placebo group and a stepwise decrease in treatment benefit of perindopril with an increasing score," the researchers reported.

Nearly 73.5 percent of patients in the genetically defined subgroup responded to perindopril, while the remaining 26.5 percent appeared to derive no benefit from treatment. "An interaction effect of similar direction and magnitude, although not statistically significant, was observed in a preliminary confirmatory analysis of over 1,000 patients with cerebrovascular disease, who were treated with perindopril or placebo from the [Perindopril Protection Against Recurrent Stroke Study] trial," researchers stated.

According to the study authors, this is the first analysis to identify gene variants linked to ACE inhibitor response. "Such individualized therapy could revolutionize medical drug therapy by prescribing drugs only to those patients most likely to benefit from the therapy," study authors said. "This would not only increase efficacy, but also decrease unnecessary treatment of patients and avoid unwanted side effects, thereby decreasing the overall costs."

Brugts did not respond to questions regarding the study ahead of press time. Perindopril is marketed under the brand name Aceon by Abbott. Several generic versions of the drug exist from Ivax Pharmaceuticals, Lupin, Aurobindo Pharmaceuticals, Roxane, and Apotex.

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