乌鸦传媒

For peripheral artery disease (PAD), using a more potent antiplatelet agent -- ticagrelor (Brilinta) -- wasn't better than standard clopidogrel (Plavix) for outcomes in the randomized EUCLID trial.

After a median of 30 months' follow-up, the combined endpoint of cardiovascular death, MI, and ischemic stroke occurred at similar rates between ticagrelor and clopidogrel recipients (10.8% versus 10.6%, HR 1.02, 95% CI 0.92-1.13).

There was no difference in acute limb ischemia (1.7% for both groups, HR 1.03, 95% CI 0.79-1.33) or major bleeding (1.6% for both groups, HR 1.10, 95% CI 0.84-1.43) rates either, , of Duke University Medical Center in Durham, N.C., reported at the American Heart Association meeting in New Orleans and simultaneously online in the.

What's more, patients on ticagrelor had to discontinue their drugs more often the clopidogrel group because of dyspnea (4.8% versus 0.8%, P<0.001) and minor bleeding (2.4% versus 1.6%, P<0.001), two well-described side effects of the more potent antiplatelet.

"In an era when we have to be looking at cost effective care, this may steer our treatment at least in the patient in whom we're using the agent specifically for peripheral vascular disease, not one who's had a recent MI or acute coronary syndrome," , president of the American College of Cardiology, told 乌鸦传媒, noting the generic availability of clopidogrel.

"Our findings show the hazards of extrapolating evidence from patients with coronary artery disease [CAD] to those with PAD," the authors wrote, in a nod to prior findings that ticagrelor trumped clopidogrel.

How can the contrasting data be reconciled? Patel suggested that he and his colleagues studied stable patients with a different biology than say, those from the PLATO trial.

Discussing the EUCLID trial at AHA, , of University of Florida in Gainesville, agreed and pointed to the exclusion of patients who were poor metabolizers of clopidogrel, or those who lacked enzymes responsible for converting the prodrug to an active compound.

Excluding individuals who couldn't metabolize clopidogrel may have been what allowed clopidogrel to match ticagrelor for PAD, Pepine suggested.

Furthermore, ischemic stroke was less common among ticagrelor recipients, occurring among 1.9% of patients (versus 2.4% of clopidogrel group, P=0.03).

The discussant suggested a difference in blood pressure may be at play: Pepine cited the DISPERSE-2 study that found elevated hypertension with clopidogrel use.

The double-blind EUCLID trial randomized 13,885 patients with PAD to monotherapy with ticagrelor or clopidogrel. Patients were included if they had an ankle-brachial index of 0.80 or under or had received prior revascularization of the lower limbs.

The ticagrelor and clopidogrel groups had 29.1% and 28.9% rates of concomitant clinical CAD on baseline, respectively. Median age was 66, with 72% of participants being men.

Missing from the trial were data on the impact of aspirin on events.

"Clearly, many knowledge gaps remain relative to PAD," Pepine emphasized, calling for researchers to fill in the gaps regarding optimal antiplatelet therapy to prevent cardiovascular and limb-related events; the role of additional medical therapies for claudication; and what dietary intervention and drugs in addition to statins can do to prevent and modify PAD.

But a different direction entirely may be needed, , of the University Hospital, Nijmegen, the Netherlands, commented in an interview with 乌鸦传媒.

Citing the failure of dual antiplatelet therapy to do better than monotherapy in PAD patients in the CHARISMA trial, looking at anticoagulants might be a better approach than a stronger antiplatelet attack, he suggested.

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