AHA 2016: Ticagrelor Not Superior for PAD

In accordance with the American Heart Association's new guidelines on treating peripheral artery disease, many cardiologists already recommend medications to inhibit blood platelets, and thereby prevent blood clotting in peripheral artery disease patients. And now, a new study may help cardiologists as they determine which medication to prescribe.

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"In someone with known vascular disease, whether it's PAD or coronary artery disease, the goal is to prevent complications, especially heart attacks," says James Froehlich, M.D., MPH, a cardiologist at the University of Michigan's Frankel Cardiovascular Center. "The question is which medication is best?"

In a surprising turn, a late-breaking clinical trial called EUCLID presented at the American Heart Association's Scientific Sessions 2016 failed to find reason to switch PAD patients to a different antiplatelet agent called ticagrelor.

Current practices

Nearly 9 million Americans have PAD, a disease that causes blockages in the arteries to the legs. Walking can be difficult, and many people experience chronic lower leg pain with walking. Statins and blood thinners are used to lower the patient's risk of heart attack, stroke or cardiovascular death, which are increased in patients with PAD.

The most affordable and most commonly recommended antiplatelet agent for preventive therapy in PAD is aspirin, Froehlich says. Clopidogrel, known as Plavix, has been shown to be slightly more effective than aspirin, but not necessarily better enough to warrant the increased price burden on most patients, he says.

Comparison to ticagrelor

In one of the largest PAD studies to date, Duke University Medical Center researchers explored whether a different antiplatelet agent that's had success in other patients would also be useful for preventive medicine in PAD patients.

Ticagrelor, also known as Brilinta, is produced by research funder AstraZeneca and was shown to be superior to clopidogrel in patients with acute coronary syndromes and stable coronary artery disease.

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But this double-blind trial of 13,885 subjects from 28 countries did not find significant differences in the number of cardiovascular events (death, stroke or heart attack) between PAD patients who received clopidogrel and PAD patients who received ticagrelor. And, more subjects had to discontinue ticagrelor due to side effects.

"The bottom line is there was no difference," says Froehlich, also a member of U-M's Institute for Healthcare Policy and Innovation. "There's no reason to choose ticagrelor over clopidogrel for secondary prevention for patients with PAD. It's also important to remember that aspirin is an effective choice at a price lower than both of those medications. We currently rarely use clopidogrel over aspirin for this indication."

The results are a reminder not to extrapolate findings from one condition to another, Froehlich adds.

"EUCLID demonstrates why the studies must be done," Froehlich says. "Only a randomized trial could answer this question even though it seemed logical to extrapolate the ticagrelor benefits from coronary disease to PAD."

Moving toward personalized medicine

The EUCLID study is also unique in its use of genetic screening. Subjects were screened for a gene mutation that makes them resistant to clopidogrel, or Plavix. Those who were Plavix resistant were excluded.

"This is one of the first major studies that included in its criteria genetic susceptibility to a medication," Froehlich says. "It helps us understand who does and does not benefit from certain therapies."