The Role of Dipyridamole in the Secondary Prevention of Stroke
ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomized controlled trial. Lancet. 2006 May 20;367(9623):1665-1673.
Background
To date, studies have resulted in inconsistent results in trials of aspirin versus aspirin in combination with dipyridamole for secondary prevention of ischemic stroke. Four early, smaller studies have yielded non-significant results, in contrast to the statistically significant relative risk reduction seen with the addition of dipyridamole to aspirin in the European Stroke Prevention Study 2 (ESPS-2).1-2
Methods
The European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) study group conducted a prospective randomized controlled trial of 2,763 patients with transient ischemic attacks or minor ischemic stroke of presumed arterial origin who received aspirin (30-325 mg daily) with or without dipyridamole (200 mg twice daily) as secondary prevention. The primary outcome for this study was a composite of death from vascular causes, nonfatal stroke, nonfatal myocardial infarction, or major bleeding complication. Mean follow-up of patients enrolled was 3.5 years.
Results
In an intention-to-treat analysis, the primary combined endpoint occurred in 16% (216) of the patients on aspirin alone (median aspirin dose was 75 mg in both groups) compared with 13% (173) of the patients on aspirin plus dipyridamole. This result was statistically significant, with an absolute risk reduction of 1% per year. As noted in other trials, patients on dipyridamole discontinued their study medication more frequently than patients on aspirin alone, mostly due to headache.
Conclusions
The results of this trial, taken in the context of previously published data, support the combination of aspirin plus dipyridamole over aspirin alone for the secondary prevention of ischemic stroke of presumed arterial origin. Addition of these data to the previous meta-analysis of trials resulted in a statistically significant risk ratio for the composite endpoint of 0.82 (95% confidence interval, 0.74-0.91).1
Commentary
Ischemic stroke and transient ischemic attacks remain a challenge to effectively manage medically and are appropriately greatly feared health complications for many patients, resulting in significant morbidity and mortality. Prior studies of secondary prevention with aspirin therapy have demonstrated only a modest reduction in vascular complications in these patients.3-4
The results of this trial are consistent with data from the Second European Stroke Prevention Study, and in combination, these data confirm that the addition of dipyridamole for patients who can tolerate it offers significant benefit.2 The magnitude of the effect results in a number needed to treat of 100 patients for one year to prevent one vascular death, stroke, or myocardial infarction. Given the clinical significance of these outcomes, many patients may prefer a trial on combination therapy.
References
- Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86.
- Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1-13.
- Warlow C. Secondary prevention of stroke. Lancet. 1992;339:724-727.
- Algra A, van Gijn J. Cumulative meta-analysis of aspirin efficacy after cerebral ischaemia of arterial origin. J Neurol Neurosurg Psychiatry. 1999 Feb;66(2):255.
The Effectiveness of CTA in Diagnosing Acute Pulmonary Embolism
Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006 Jun 1;354(22):2317-2327.
Background
The Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) trial was designed to answer questions about the accuracy of contrast-enhanced multidetector computed tomographic angiography (CTA). Recent studies of the use of single-row or multidetector CTA alone have suggested a low incidence of pulmonary embolism in follow-up of untreated patients with normal findings on CTA.