Stroke and Acute Coronary Syndrome: How to Prevent Recurrence

How best to prevent future vascular events in a patient who has a history of stroke and an acute coronary syndrome?

Several studies have compared clopidogrel, aspirin, or a combination for secondary prevention. In the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study,¹ Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial,² and Aspirin and Clopidogrel Compared With Clopidogrel Alone After Recent Ischaemic Stroke or Transient Ischaemic Attack in High-Risk Patients (MATCH) study,³ clopidogrel and combination therapy were more effective than aspirin alone in preventing vascular events.

THE CARDIOLOGIST’S CHOICE

Clopidogrel has become standard therapy for secondary prevention after a myocardial infarction. There is one drawback, however. The combination of clopidogrel and aspirin may increase the risk of bleeding. In patients in the MATCH study who had a recent stroke or transient ischemic attack (TIA), aspirin and clopidogrel led to a greater absolute increase in bleeding than absolute reduction in vascular events, compared with aspirin alone.³

THE NEUROLOGIST’S CHOICE

Let us look at secondary prevention from the neurologist’s point of view. The Second European Stroke Prevention Study (ESPS-2) compared aspirin with aspirin plus extended-release dipyridamole (ASA/ER-DP) after stroke or TIA.⁴ Combination ASA/ER-DP reduced the relative risk of secondary strokes by 23% compared with aspirin alone. Thirty-six percent of the patients in this study also had coronary disease. In this group, ASA/ER-DP was as effective in preventing stroke and death as it was in other patients in the study. Unlike the CAPRIE, CURE, and MATCH studies, ESPS-2 did not demonstrate an increase in bleeding complications with combination therapy compared with aspirin alone.

From a neurologist’s perspective, the choice for secondary prevention after stroke or TIA seems to be ASA/ER-DP. But which therapy is best if your patient has a history of both cardiac and neurovascular events?

A SUGGESTION-AND A CAVEAT

Recently, a neurologist addressed this potential conflict. Gebel suggested clopidogrel and aspirin if the patient’s most recent vascular event was cardiac and ASA/ER-DP for treatment after stroke or TIA.⁵

What if your patient is already taking ASA/ER-DP after a stroke and has an acute coronary syndrome? The definitive answer is not available. However, a word of caution is in order. Because the increase in bleeding events in patients taking clopidogrel and aspirin in the MATCH study exceeded the absolute reduction in vascular events, it would seem prudent not switch to this combination therapy in patients with stroke or TIA.

The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial is currently enrolling 15,500 stroke patients. It will be the first study to compare ER-DP with clopidogrel.

References:

REFERENCES:

1.

CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).

Lancet

. 1996; 348:1329-1339.

2.

Yusuf S, Zhao F, Mehta SR, et al; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.

N Engl J Med

. 2001;345:494-502.

3.

Diener HC, Bogousslavsky J, Brass LM, et al; MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial.

Lancet

. 2004;364:331-337.

4.

Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

J Neurol Sci

. 1996;143:1-13.

5.

Gebel JM Jr. Secondary stroke prevention with antiplatelet therapy with emphasis on the cardiac patient: a neurologist’s view.

J Am Coll Cardiol

. 2005; 46:752-755.