Genotyping spares bleeding with cardiovascular drugs

2019 09 05 21 14 7857 Heart Pulmonary Trunk 400

Genotype-guided treatment meant less bleeding for some patients who underwent primary percutaneous coronary intervention (PCI) and were taking blood thinners in a Dutch study presented at the European Society of Cardiology and World Congress of Cardiology joint meeting, held August 31 to September 4 in Paris.

The randomized study showed that the P2Y12 inhibitor clopidogrel (Plavix) was as effective as newer drugs in the class -- ticagrelor (Brilinta) or prasugrel (Effient) -- for preventing thrombotic events in patients undergoing PCI with stent implantation, but with significantly less bleeding. In addition to the presentation at the meeting, results were reported by Dr. Jurriën ten Berg, PhD, of St. Antonius Hospital in Nieuwegein, the Netherlands, and colleagues in the New England Journal of Medicine online September 3.

"The results for both the thrombotic and bleeding outcomes of the trial are in line with data from observational studies and smaller trials investigating a genotype-guided strategy," the authors wrote in NEJM.

Putting antiplatelet therapies to the test

Plavix is a household name and was revolutionary in its day, but it doesn't work in about one-third of the white population who have CYP2C19 loss-of-function alleles and can't metabolize the drug. Platelet function testing, however, can help identify who will respond to treatment. Today, clopidogrel is available as a generic, but it competes with the branded and therefore more expensive drugs ticagrelor and prasugrel, both of which are more potent and don't require platelet function testing.

The study of 2,488 patients who were undergoing PCI with stent implantation compared the effects of 12 months of treatment with clopidogrel for carriers of loss-of-function alleles in one arm versus standard treatment with either ticagrelor or prasugrel for noncarriers in a second arm. Both cohorts also received aspirin.

The study was conducted at 10 European sites and was funded by the Netherlands Organisation for Health Research and Development. Genotype testing was performed with the TaqMan StepOnePlus test (Applied Biosystems) at a central lab or with the point-of-care Spartan RX assay (Spartan Bioscience).

For the primary efficacy end point -- a composite of adverse cardiovascular events, including death from any cause and heart attack -- outcomes were similar. The rate of events was 5.1% for the genotyped group compared with 5.9% for the comparator, which was not a significant difference.

There was a significant difference (p = 0.04), however, in bleeding events: The rate was 22% lower in the genotyped group (9.8%) than in the comparator group (12.5%). The rates of major bleeding were similar; the benefit was driven mostly by differences in minor bleeding.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is "essential" for preventing recurrent thrombotic events in ST-segment elevation myocardial infarction (STEMI) PCI stent implantation, the authors noted.

"Current guidelines favor the more potent platelet inhibitors ticagrelor and prasugrel over clopidogrel because the drugs are more effective for the prevention of thrombotic events," they wrote. "However, this greater efficacy comes with a higher risk of bleeding."

It's possible to start with a newer agent and then switch, but this requires more office visits for patients, they noted.

Although the guidelines favor ticagrelor and prasugrel, clopidogrel is still widely used in many countries, ten Berg commented in an email to

"If you use genotyping, clopidogrel is as effective as the other two," he said. "And yes, it will probably save money, but the most important finding is it saves bleeds, which [is] very important for patients."

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