Combination Anticoagulant and Antiplatelet Therapy in Acute Stroke

The Big Heart Disease Lie

Cure for Cardiovascular Disease Found

Get Instant Access

The Cochrane group examined (a) whether the addition of UFH or LMWH to anti-platelet agents offers any net advantage over antiplatelet monotherapy for acute stroke, and (b) the effectiveness of anticoagulants compared to antiplatelets in acute ischemic stroke.17 They included 4 trials of 16,558 patients, each of which specified aspirin (160-333 mg daily) as the control, and all of which randomized patients within 14 days of stroke onset. The anticoagulants tested were UFH and LMWH. Almost 98% of the patients were followed up for 6 months.

Compared with aspirin monotherapy, anticoagulant treatment was associated with a small but significant increase in the number of deaths at the end of follow-up (OR 1.10, 95% CI 1.01-1.29), equivalent to 20 more deaths per 1000 patients treated with anticoagulants. Subgroup analysis showed that the combination of low-dose UFH and aspirin was associated with a marginally significant reduced risk of any recurrent stroke (OR 0.75, 95% CI 0.56-1.03) and a marginally significant reduced risk of death at 14 days (OR 0.84, 95% CI 0.69-1.01), with no clear adverse effect on death at the end of follow-up.

As in previous reviews they also found an increased risk of sICH (OR 2.27, 95% CI 1.49-3.46), equivalent to 10 more (95% CI 0-10 more) sICHs per 1000 patients treated. An interaction by anticoagulant dose on sICH was observed (p = 0.01), with a greater risk in trials using high-dose anticoagulants (OR 3.24, 95% CI 2.09-5.04) as opposed to low-dose anticoagulants (OR 1.29, 95% CI 0.72-2.32). A similar dose-response relationship was observed when comparing UFH plus aspirin with aspirin monotherapy in the IST trial. Compared directly with aspirin, anticoagulants were associated with a nonsignificant increase in the risk of recurrent stroke (OR 1.20, 95% CI 0.99-1.46), equivalent to 10 more recurrent strokes per 1000 patients treated.

This was largely influenced by the high-dose UFH group in 1ST (OR 1.38, 95% CI 1.05-1.82). An interaction by UFH dose (p = 0.01) on recurrent stroke risk with combination UFH-aspirin therapy compared to aspirin monotherapy was observed, with a trend toward increased risk of recurrent stroke with high-dose UFH + aspirin (OR 1.22, 95% CI 0.92-1.62) and a trend toward reduced risk with low-dose UFH + aspirin (OR 0.75, 95% CI 0.56-1.03), equivalent to 10 fewer (95% CI 020 fewer) recurrent strokes per 1000 patients treated. They found a small, but significant benefit of LMWH over aspirin in the prevention of symptomatic DVT, equivalent to 10 (95% CI 0-30) fewer DVTs per 1000 patients treated. Compared with aspirin, anticoagulants were associated with nonsignificantly fewer symptomatic PEs (OR 0.85, 95% CI 0.55-1.32). There were fewer PEs with the combination of UFH and aspirin (OR 0.58, 95% CI 0.34-1.00), equivalent to 5 fewer (CI 0-10) PEs per 1000 patients treated. However, the overall incidence of symptomatic DVT and PE was low (1.1% and 0.7%).

Overall no evidence was found to support the claim that anticoagulants offer a net advantage over aspirin in patients with acute ischemic stroke. There was evidence, however, to suggest that combination anticoagulant and aspirin therapy was associated with a small increase in the number of deaths at the end of follow-up, equivalent to 20 more deaths per 1000 patients treated. This adverse effect can probably be attributed partly to the 10 extra sICHs, and the 5 extra major extracranial hemorrhages per 1000 patients treated with combination anticoagulant/ aspirin therapy.

Was this article helpful?

0 0
Your Heart and Nutrition

Your Heart and Nutrition

Prevention is better than a cure. Learn how to cherish your heart by taking the necessary means to keep it pumping healthily and steadily through your life.

Get My Free Ebook


Post a comment