Treating Patients Who Have Recurrent Strokes While Taking Aspirin

 

 

Côté R et al. Neurology 2014 Feb 4.

Long-term aspirin plus clopidogrel wasn’t better than aspirin alone.

In the previously published SPS3 trial, 3000 patients who experienced lacunar strokes during the previous 6 months were randomized to receive aspirin alone or aspirin plus clopidogrel. During several years of follow-up, dual antiplatelet therapy did not prevent recurrent stroke and increased risk for major hemorrhage and death (NEJM JW Neurol Aug 29 2012). Now, in a post hoc analysis from this study, researchers present data on the 838 patients who already had been taking prophylactic aspirin at the time of the lacunar stroke that qualified them for the trial.

Outcomes in this subgroup mirrored those of the larger study. During mean follow-up of 3.5 years, the annual stroke rate was 3% in both the aspirin monotherapy and dual antiplatelet therapy treatment groups. However, annual mortality was higher with dual therapy than with aspirin alone (2.9% vs. 1.4%; P=0.004), and gastrointestinal bleeding was more common with dual therapy.

COMMENT

In this analysis, aspirin plus clopidogrel was not more effective than aspirin alone for preventing subsequent strokes in patients with previous lacunar strokes that occurred during aspirin therapy. Note that SPS3 patients were randomized an average of 2.5 months after their index lacunar strokes. In contrast, in the recently published CHANCE trial (NEJM JW Neurol Jun 26 2013), short-term dual therapy was more effective than aspirin alone in patients with transient ischemic attack or minor stroke who were randomized within 24 hours; in that study, no distinction was made between lacunar strokes and other stroke subtypes.

Combination Antiplatelet Therapy for Transient Ischemic Attack or Minor Stroke: Does It Work?

Wang Y et al. N Engl J Med 2013 Jun 26.

Results of a study in China suggest that it might. 

To compare the effects of aspirin plus clopidogrel with aspirin alone in minor stroke or transient ischemic attack (TIA), more than 100 centers in China recruited a total of 5170 patients with a diagnosis of “high-risk” TIA or minor stroke within 24 hours of symptom onset. High-risk TIA was defined as a score of ≥4 on the ABCD2 scale, which is based on age, blood pressure, and other clinical variables. Minor stroke was defined as a score of ≤3 on the NIH Stroke Scale score.

All patients received aspirin (75–300 mg) on day 1 and 75 mg of aspirin through day 21. Those randomized to dual antiplatelet therapy received 300 mg of clopidogrel on day 1 and 75 mg on days 2 through 90, with aspirin placebo on days 22 through 90. Those randomized to aspirin alone continued on 75 mg of aspirin daily though day 90, with clopidogrel placebo on days 1 through 90.

During the 90-day follow-up period, there was a significant, 32% relative reduction in the rate of stroke with dual antiplatelet therapy (11.7% with aspirin alone, 8.2% with the combination; hazard ratio, 0.68) and a significant reduction in the combination of fatal or disabling stroke (HR, 0.75). Major extracranial or intracranial hemorrhages did not differ (0.3% in both groups).

COMMENT

Some treatments initially used for cardiac disease (e.g., thrombolysis and statins) have percolated into the prevention and treatment of stroke. Other treatments commonly used for cardiac disease, such as intravenous heparin, have not been proven useful for stroke.

What about dual antiplatelet therapy, which is effective for acute coronary syndromes? This study showed an impressive 32% relative and 3.5% absolute reduction in the rate of stroke with dual antiplatelet therapy. Asian populations differ from others with respect to the pathophysiology of stroke, such as greater frequency of intracranial stenosis. A North American study with a similar design is in progress (the POINT trial). If the second study confirms the benefits of dual antiplatelet therapy, another “cardiac” treatment could soon be applied to patients with cerebrovascular disease.