Aspirin in combination with dipyridamole is better than aspirin alone for secondary stroke prevention

A study conducted by the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group in 2006 has finally resolved the uncertainty regarding whether to use aspirin alone or in combination in patients with cerebral ischaemia. The research results collaborated with results of previous systematic reviews; prove that aspirin in combination with dipyridamole is the superior regimen for secondary prevention of stroke. Combination therapy was associated with reduced rates of vascular deaths, stroke and myocardial infarction compared to aspirin therapy alone.

Several studies have considered the role of aspirin and other anti-platelet medications in secondary prevention of transient ischaemic attack or ischaemic stroke of presumed arterial origin. The benefits of aspirin albeit small, are well documented and generally accepted. However, researchers have long been attempting to identify better methods of secondary stroke prevention for the future. Of interest has been the role of combination therapy, in particular aspirin and dypyridamole (which alone has an even more modest effect compared to aspirin), for anti-thrombotic therapy. Until recently results had been equivocal. Two previous large trials found that the combination of clopidogrel and aspirin provided no additional benefits compared with either of these drugs alone. Whilst the second European Stroke Prevention Study (ESPS 2) conducted earlier had suggested a relative risk reduction of vascular events following the addition of dipyridamole to aspirin therapy. Other smaller studies also produced conflicting results. A recent issue of the Lancet published results of the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) which finally confirms the benefits of dual therapy using aspirin and dipyridamole. Results were based on 2739 patients confirmed to have had a transient ischaemic attack or ischaemic stroke of presumed arterial origin within 6 months of entering the trial. Patients were randomised to receive aspirin (30-325 mg daily based on physician prescriptions) alone or in combination with dipyridamole (200 mg twice daily). Patients were followed for a mean of 3.5 years primarily considering the incidence of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction or major bleeding complications. Results showed a significant benefit of dual therapy over aspirin therapy alone in terms of primary outcome events. This is consistent with the aforementioned ESPS 2 trial. In addition, researchers performed a new systematic review which showed a robust treatment effect with the overall risk ratio for the composite of vascular death, stroke, or myocardial infarction being measured as 0.82. However, an important consideration is the large proportion of patients receiving the combination of aspirin and dipyridamole who discontinued treatment due to side effects, a substantially greater number than aspirin treatment alone. The most commonly reported side effect was headaches, which is a known side effect of dipyridamole that has also been reported in previous studies. Furthermore, whilst final auditing of outcome events was blinded, treatment was open so the study has been criticised for its theoretical potential for bias. The current results of the ESPRIT research and combined meta-analysis is sufficient evidence to adopt combination therapy with dipyridamole and aspirin into routine clinical practice, along with other primary stroke prevention techniques (such as lifestyle modifications). This serves to benefit substantial numbers of patients in Australia who suffer cerebral ischaemia of arterial origin. Further research is required to determine suitable methods to reduce adverse effects of dipyridamole (such as dose titration) to promote successful long term use. In addition, new anti-platelet therapies and acute stroke treatments are further areas of current research. Reference:ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.Lancet 2006; 367: 1665-73.