Despite the apparent additive benefit derived from extended-release dipyridamole plus aspirin, no evidence was found for an increase in adverse outcomes. Adverse gastrointestinal events in the combination therapy group were comparable with those noted with aspirin monotherapy, with an increased incidence of headache.20
As in ESPS-2, the European/Australian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) investigated the combination of aspirin and dipyridamole (principally extended-release dipyridamole). Using a primary combined endpoint of vascular death, nonfatal stroke, nonfatal myocardial infarction, and major bleeding complications, ESPRIT confirmed aspirin plus dipyridamole to be superior to aspirin monotherapy in reducing these complications.21 An overall risk ratio of 0.82 for the composite endpoint (P=0.0003) was determined in a meta-analysis of the trials comparing aspirin alone to aspirin plus dipyridamole.21 (See Figure 1, p. 39.)
An in-progress prospective secondary stroke prevention study, the Prospective Regimen for Effectively Avoiding Second Strokes (PRoFESS) study, which consists of 15,500 patients with a recent history of ischemic stroke, will provide the first head-to-head comparison of clopidogrel monotherapy with the extended-release dipyridamole plus aspirin combination. The two antiplatelet regimens will be evaluated through a 2 x 2 design in the presence and in the absence of the antihypertensive telmisartan, with results expected in 2007. PRoFESS findings should help to clarify the comparative efficacy of clopidogrel versus extended-release dipyridamole plus aspirin with regard to the primary endpoint (time to first stroke recurrence) and a vascular events composite endpoint.
Antiplatelet Treatment Guidelines
The American Academy of Neurology guidelines recommend the use of aspirin within 48 hours of stroke symptom onset (except when tissue plasminogen activator treatment has been used or is anticipated) to reduce mortality and prevent early stroke recurrence.22 A more extensive set of evidence-based guidelines for antiplatelet and antithrombotic use following ischemic stroke, including recommendations for secondary event prevention, was developed in 2004 by the American College of Chest Physicians (ACCP).23 The primary recommendation (Grade 1A) is to provide treatment with an antiplatelet agent (i.e., aspirin at 50 to 325 mg/day, extended-release dipyridamole at 200 mg plus aspirin at 25 mg twice daily, or clopidogrel at 75 mg/day) following noncardioembolic stroke. The ACCP has also suggested that extended-release dipyridamole plus aspirin (Grade 2A) or clopidogrel (Grade 2B) may be preferable to aspirin monotherapy. This suggestion does include the caveat that this “places a relatively high value on a small absolute risk reduction in stroke rates, and a relatively low value on minimizing drug expenditures.”23
When the post-stroke patient is prepared for discharge, place the highest priority on ensuring an effective continuum of care. Comprehensively review all medications, including those prescribed for prevention of secondary events, with the patient and family or caregivers. Explain the purpose of each medication, along with the consequences of poor compliance or discontinuation; reinforce the need for lifelong therapy for stroke prevention and amelioration of stroke risk factors at every opportunity.
A key step in establishing the continuum of care is to gain buy-in from the primary care provider for continuing medical therapy and follow-up. If appropriate, cite current guidelines from the American Academy of Neurology, the American College of Chest Physicians, and the American Stroke Association. Occupational or physical therapy, if indicated, should be planned before discharge and coordinated with the primary care provider for continued follow-up. This evaluation may also result in a recommendation for inpatient rehabilitation or, in the interim, a skilled nursing facility placement.
Given the improvement that many patients realize over the short term, staged discharge to a skilled nursing facility may be followed after a short interval by a stay at an inpatient rehabilitation facility. Coordination of this staged approach must be carefully implemented, as it is easy for this to fall through the cracks during transitions of care.