Debunking the gospel of heparin for strokes

Portraying heparin as a religion may be an exaggeration, but not so far from the truth.

An Internal Medicine 2009 session on stroke and transient ischemic attack opened with a photo of a stroke neurologist bowing before a vial of heparin flanked by two candles. Portraying heparin as a religion may be an exaggeration but not so far from the truth, said presenter Scott E. Kasner, MD, director of the Comprehensive Stroke Center at the University of Pennsylvania.

The “heparinism gospel” teaches that antithrombotic therapy with heparin prevents recurrent embolism, stroke propagation of thrombus and systemic thromboembolism, not to mention its anti-inflammatory and neuroprotective properties, said Dr. Kasner. The thinking goes that it's better to treat every stroke patient with heparin, in the absence of contraindications, because doctors cannot predict which patients will have progression or re-embolization, and the risks of heparin are low.

The problem is that there is no evidence to support that gospel, said Dr. Kasner. In 1997, for example, the International Stroke Trial (IST), which included almost 20,000 patients, randomized patients to subcutaneous heparin versus “avoid heparin” and aspirin versus “avoid aspirin” groups and found no clear indication or contraindication for either aspirin or heparin. The trial found that heparin was associated with fewer recurrent ischemic strokes but more hemorrhagic stroke, so had no net benefit.

Two other major randomized trials concluded that acute anticoagulation was ineffective for stroke, said Dr. Kasner. But while neurologists wanted a definitive clinical trial, many did not accept the results, said Dr. Kasner. “It was heparinism heresy.”

Some stroke subgroups may benefit from some form of anticoagulation, he said. In the IST, for example, heparin reduced the risk of recurrent stroke by 2.1% but increased the risk of hemorrhage by 1.7% in over 3,000 patients with atrial fibrillation at the time of randomization. Again, there was no net benefit.

Evidence suggests that there is no rush to give heparin in most patients with a cardioembolic source of stroke, said Dr. Kasner. He recommended waiting 48 hours in patients with minor strokes and five to seven days for major strokes.

Anticoagulation with warfarin has proven better than aspirin in preventing recurrent strokes due to cardioembolism, but antiplatelet medication is better in almost all other cases, he said. “Aspirin, ticlopidine, clopidogrel and dipyridamole (DP) plus aspirin are as effective, safer, easier to use and less expensive.”

In the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) Trial, which compared combinations of telmisartan with either ER-DP and aspirin, clopidogrel, or placebo, the rate of first recurrent stroke was similar between the combination therapy and the single antiplatelet agent treatment groups. The findings show that ER-DP plus aspirin combination therapy is as effective as clopidogrel in reducing stroke recurrence with no major safety differences, said Dr. Kasner.

Clopidogrel is often preferred and may be the best choice for prevention and treatment of stroke because it is easer to administer, said Dr. Kasner. However, with aspirin a fraction of the cost of the other drugs, “There is a population-wide argument for aspirin from a cost standpoint.”