Key result
Aspirin plus dipyridamole cuts composite vascular events and bleeding ~20% vs. aspirin alone.
Why the study?
Results of trials comparing aspirin plus dipyridamole versus aspirin alone for secondary prevention after ischaemic stroke of arterial origin were inconsistent.
Does aspirin plus dipyridamole reduce the risk of a composite of vascular death, non-fatal stroke, non-fatal myocardial infarction, or major bleeding compared to aspirin alone in patients with recent transient ischaemic attack or minor stroke?
RCT (n=2,739)
Open-label treatment, blinded outcome auditing
Randomised controlled trial
Does aspirin plus dipyridamole reduce the risk of a composite of vascular death, non-fatal stroke, non-fatal myocardial infarction, or major bleeding compared to aspirin alone in patients with recent transient ischaemic attack or minor stroke?
The combination of aspirin and dipyridamole significantly reduces the risk of vascular events compared to aspirin alone for secondary prevention after cerebral ischemia, though it carries a higher rate of discontinuation due to headaches.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“A major problem with ESPRIT is that the dose of aspirin was left to the discretion of the treating physician. Forty-eight percent of the patients were treated with 50 mg/day or less of aspirin, and only 5% were treated with at least 300 mg/day. The low dose that many of the patients received may not have been adequate and may explain why there was a significant difference from the aspirin/dipyridamole combination.”
“In the ESPRIT study, half the patients on aspirin alone received less than 75 mg aspirin and therefore might have been underdosed. The putative benefit of the combination seems to occur only after 2 years, at a time when 27% of the patients had already given up taking the combination (compared with 8% on aspirin). Nevertheless, the intention-to-treat analysis reveals greater effects for all efficacy endpoints than the on-treatment analysis. The inconsistency indicates that patients might profit more if they discontinue treatment early.”
“If a similar association between bleeding and outcome existed in ESPRIT, it would account, at least partly, for the superior efficacy of aspirin and dipyridamole compared with aspirin alone, and would underscore the importance of developing and adopting safer treatments that reduce the risk of bleeding while maintaining antithrombotic efficacy.”
Supports aspirin-dipyridamole over aspirin alone after TIA or minor stroke; extends prior meta-analyses confirming vascular event reduction.
BACKGROUND: Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty. METHODS: We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070). FINDINGS: Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache. INTERPRETATION: The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.
No takes yet. Share an insight, caveat, or question.
‡ (2006) conducted an RCT in Transient ischaemic attack or minor stroke of presumed arterial origin (n=2,739). Aspirin plus dipyridamole vs. Aspirin alone (30-325 mg daily) was evaluated on Composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication (HR 0.80, 95% CI 0.66-0.98). Aspirin plus dipyridamole reduced the primary composite of vascular death, non-fatal stroke, non-fatal myocardial infarction, or major bleeding compared to aspirin alone (HR 0.80, 95% CI 0.66-0.98; ARR 1.0% per year).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: