Using Ticagrelor with Antiplatelet cuts the risk of stroke

Prolonged use of ticagrelor (Brilinta) together with aspirin following a myocardial infarction (MI) decreases the risk of stroke, or death from cardiovascular disease. However, there will be major bleeding risk.

Patients randomized 1 to 3 years after an MI to a median 33 months of dual antiplatelet therapy with ticagrelor cut those risks compared with a similar duration of aspirin alone, Marc P. Bonaca, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues reported online in the New England Journal of Medicine.

The primary composite of cardiovascular death, MI, or stroke at 3 years of treatment occurred in:

  • 9.04% on placebo plus aspirin
  • 7.77% on 60-mg ticagrelor twice daily and aspirin (hazard ratio 0.84, 95% CI 0.74 to 0.95)
  • 7.85% on 90-mg ticagrelor twice daily and aspirin (HR 0.85, 95% CI 0.75-0.96)

Rates of major bleeding by Thrombolysis in Myocardial Infarction (TIMI) criteria was more than doubled ticagrelor, at 2.60% with 90-mg and 2.30% with 60-mg versus 1.06% with placebo (both P<0.001).

But the most worrisome forms — intracranial hemorrhage and fatal bleeding — were not elevated with ticagrelor. The rates were 0.63% on 90 mg, 0.71% on 60 mg, and 0.60% on placebo.

The 60-mg dose is probably the better choice because it was better tolerated and caused less bleeding, said PEGASUS principle investigator Marc S. Sabatine, MD, MPH, who reported the results at a late-breaking clinical trial session at the American College of Cardiology (ACC) meeting in San Diego.

The results, confirming top-line results released by drugmaker AstraZeneca in January from the 21,162-patient trial, might make a greater case for ticagrelor’s use in secondary prevention but weren’t seen as a home-run for the drug.

“The one piece of data we have right now that really supports ticagrelor is in ST-segment MI in the PLATO study,” noted W. Douglas Weaver, MD, of the Henry Ford Hospital in Detroit and a past president of the ACC.

Aside from problems found in its conduct, “PLATO didn’t have much effect on people treated in the United States versus treated in Europe, so I think a lot of doctors wanted another piece of evidence this drug could be superior in some other setting,” he told MedPage Today. “So therefore I do think this is an important study.”

But Richard A. Chazal, MD, ACC vice president and medical director of the heart and vascular institute at Lee Memorial Health System in Fort Myers, Fla., told MedPage Today the only thing that can be gleaned from PEGASUS is that “both doses of the drug are effective.”

Even that efficacy may really be a somewhat zero-sum game, John F. Keaney Jr., MD, of the University of Massachusetts Medical School in Worcester, said in an accompanying editorial.

“On the basis of the 60-mg ticagrelor dose, treating 10,000 patients for 1 year would prevent approximately 42 primary endpoint events and produce approximately 31 TIMI major bleeding events — close to an even proposition,” he wrote.

He suggested that the data could prompt speculation as to whether dual platelet inhibition with high-potency agents is “approaching the point of diminishing returns.”

However, Weaver and others saw the findings as confirmation of the recent benefits seen with 30 months versus the typical 12 months of dual antiplatelet therapy (DAPT) after stenting in the landmark DAPT trial.

“Now to me it’s confirmatory that you can change outcomes by inhibiting this for another year,” conference chair Athena Poppas, MD, director of the echocardiography lab at Rhode Island Hospital and director of cardiovascular imaging at its Cardiovascular Institute, both in Providence.

The message, again, as in the DAPT trial may be that it’s not just the early risk that needs to be addressed, Weaver suggested.

“In the past, cardiologists kind of treated the procedure. You could stent and think it’s over with. But it’s not over with, the disease is still there,” he told MedPage Today. “Here’s a piece of evidence that patients who don’t have bleeding problems, they need to stay on these drugs — perhaps ticagrelor in particular — for a long period of time.”

Chazal argued that the ticagrelor findings cannot be extrapolated to a comparison with clopidogrel (Plavix).

“Could clopidogrel do the same thing? We don’t know. We need another study,” Weaver said.

Poppas was more willing to extrapolate. “Which drug you choose is a conversation with the patient, and cost is a big issue,” she said.

Clopidogrel has an off-patent price tag of less than $10 for a month’s supply, compared with $350 for ticagrelor.

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