While prasugrel (Effient®) or ticagrelor (Brilinta®) have replaced clopidogrel (Plavix®) in the management of acute coronary syndromes, I wonder why we haven’t seen much of their infiltration in the market for secondary prevention of stroke.  Perhaps these therapies have been evaluated but the evidence has not been convincing at all. In fact, there is evidence of potential harm that is worth noting.

Prasugrel

Prasugrel is actually contraindicated in patients with a history of TIA (transient ischemic attack) and stroke. This contraindication stems mainly from the safety data collected in TRITON-TIMI 38 in 2007 – a study designed to evaluate the efficacy of dual antiplatelet therapy of prasugrel with ASA as compared to clopidogrel with ASA in patients with acute coronary syndromes with scheduled percutaneous coronary intervention.

The study found that the dual antiplatelet group with prasugrel and ASA developed significantly more non-CABG related major bleeding which include both life threatening bleed and fatal bleeding:

Major Bleeding in Prasugrel.jpg

It was found the the majority of the bleeding was driven by two risk factors: patients with history of stroke or transient ischemic attack and elderly, frail patients. Given the clinical significance of the above safety data, prasugrel is contraindicated in individuals with a history of TIA or stroke.

Ticagrelor

Unlike prasugrel, ticagrelor is not contraindicated in patients with a history of stroke or TIA. Ticagrelor was recently evaluated for its efficacy in secondary stroke prevention in SOCRATES.  In this double-blind controlled study, ticagrelor was compared with aspirin in about 13000 patients for secondary stroke prevention.   The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.  As listed in the abstract of SOCRATES, the results are as follow:

  • During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P = 0.07).
  • Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00).
  • Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.

While these results show a trend with greater benefits seen in the ticargrelor group, the difference is statistically insignificant. The authors have concluded that ticagrelor is not superior to aspirin in the secondary prevention of stroke or cardiovascular events.

So for now, our antiplatelet options are still primarily aspirin or clopidegrel for secondary stroke prevention.

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