Therapeutics Systematic review and meta-analysis
Meta-analysis finds benefit for dual antiplatelet therapy but limitations preclude changing standard mono antiplatelet therapy approach for acute non-cardioembolic ischaemic stroke or transient ischaemic attack 10.1136/eb-2013-101649
76 patients. PubMed was searched from January 2011 to November 2012 for potentially eligible studies. A manual search of references from original articles and reviews was performed. All data were analysed using Cochrane Review Manager. Primary analyses were performed for each outcome with trials subdivided by different drugs assessed. Results were presented as risk ratios (RR) and 95% CIs.
Findings Compared with mono antiplatelet therapy, dual antiplatelet therapy reduced recurrent stroke (RR=0.69, 95% CI 0.60 to 0.80) and composite outcome of stroke, TIA, acute coronary syndrome and all-cause mortality (RR=0.71, 95% CI 0.63 to 0.81), and insignificantly increased major bleeding (RR=1.35; 95% CI 0.70 to 2.59).
Commentary Wilbert S Aronow Division of Cardiology, New York Medical College/Westchester Medical Center, Valhalla, New York, USA Correspondence to: Dr Wilbert S Aronow, Division of Cardiology, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595, USA; [email protected]
Commentary on: Wong KSL, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack. An updated systematic review and meta-analysis. Circulation 2013;128:1656–66.
Context Current guidelines recommend aspirin, aspirin plus clopidogrel or aspirin plus extended-release dipyridamole for treatment of acute ischaemic stroke (IS) or transient ischaemic attack (TIA) to prevent recurrent stroke, myocardial infarction and cardiovascular death.1 The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial randomised 5170 Chinese patients within 24 h after the onset of IS or TIA to clopidogrel plus aspirin versus aspirin plus placebo for 90 days. Clopidogrel plus aspirin reduced recurrent stroke without increased haemorrhage.2 In recent years, various studies have attempted to assess the comparable risks and effectiveness of dual and mono antiplatelet therapy, but with conflicting results.3–5 Wong and colleagues reviewed the findings of several studies, including the CHANCE trial.
Methods A meta-analysis assessed 14 studies—a total of 9012 patients with acute IS or TIA—comparing dual versus mono antiplatelet therapy. The CHANCE trial contributed 5170 patients (57.4% of total patients). Aspirin plus clopidogrel versus aspirin was assessed in five trials in 5901 patients, aspirin plus clopidogrel versus clopidogrel in 491 patients, aspirin plus dipyridamole versus aspirin in 964 patients, aspirin plus dipyridamole versus dipyridamole in 220 patients, aspirin plus dipyridamole versus clopidogrel in 1360 patients and cilostazol plus aspirin versus aspirin in 76 patients. Twelve studies were included from a previous meta-analysis plus the CHANCE trial and one other study of
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Meta-analyses tend to overestimate efficacy of therapy because negative studies are less likely published. The present meta-analysis has numerous limitations: the study focused strongly on the CHANCE study, which provided 57.4% of the total patients; the studies varied in study populations, stroke severity, antiplatelet drugs used, onset to time of treatment, follow-up durations and other variables; finally, in some studies, only a small portion of patients were treated within 3 days of IS or TIA. Confounders might be different between patients treated with dual versus mono antiplatelet therapy in these patients. Propensity analyses need to be performed in these studies. CHANCE first investigated dual versus mono antiplatelet therapy before assessing different mono antiplatelet therapies. We do not know the extent to which clopidogrel monotherapy use from days 21 to 90 (following 21 days of dual clopidogrel plus aspirin therapy) affected difference in outcomes compared with 3 months of aspirin monotherapy. Results of ongoing clinical trials will provide more data on the efficacy and risks of dual and mono antiplatelet therapy. Until these data are available, aspirin monotherapy as currently recommended should be favoured for treatment of acute IS or TIA. If a patient develops a new IS or TIA while being treated with aspirin, use of mono clopidogrel therapy should be favoured. Competing interests None. References 1. National Collaborating Centre for Chronic Conditions (UK). National clinical guide for diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). National Institute for Health and Care Excellence (NICE) Clinical Guidelines, 2008. 2. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369:11–19. 3. Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008;359:1238–51. 4. Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PROFESS subgroup analysis. Stroke 2010;41:732–8. 5. Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomized, double-blind, placebo-controlled trial. Lancet 2004;364:331–7.
Meta-analysis finds benefit for dual antiplatelet therapy but limitations preclude changing standard mono antiplatelet therapy approach for acute non-cardioembolic ischaemic stroke or transient ischaemic attack 10.1136/eb-2013-101649
76 patients. PubMed was searched from January 2011 to November 2012 for potentially eligible studies. A manual search of references from original articles and reviews was performed. All data were analysed using Cochrane Review Manager. Primary analyses were performed for each outcome with trials subdivided by different drugs assessed. Results were presented as risk ratios (RR) and 95% CIs.
Findings Compared with mono antiplatelet therapy, dual antiplatelet therapy reduced recurrent stroke (RR=0.69, 95% CI 0.60 to 0.80) and composite outcome of stroke, TIA, acute coronary syndrome and all-cause mortality (RR=0.71, 95% CI 0.63 to 0.81), and insignificantly increased major bleeding (RR=1.35; 95% CI 0.70 to 2.59).
Commentary Wilbert S Aronow Division of Cardiology, New York Medical College/Westchester Medical Center, Valhalla, New York, USA Correspondence to: Dr Wilbert S Aronow, Division of Cardiology, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595, USA; [email protected]
Commentary on: Wong KSL, Wang Y, Leng X, et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack. An updated systematic review and meta-analysis. Circulation 2013;128:1656–66.
Context Current guidelines recommend aspirin, aspirin plus clopidogrel or aspirin plus extended-release dipyridamole for treatment of acute ischaemic stroke (IS) or transient ischaemic attack (TIA) to prevent recurrent stroke, myocardial infarction and cardiovascular death.1 The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial randomised 5170 Chinese patients within 24 h after the onset of IS or TIA to clopidogrel plus aspirin versus aspirin plus placebo for 90 days. Clopidogrel plus aspirin reduced recurrent stroke without increased haemorrhage.2 In recent years, various studies have attempted to assess the comparable risks and effectiveness of dual and mono antiplatelet therapy, but with conflicting results.3–5 Wong and colleagues reviewed the findings of several studies, including the CHANCE trial.
Methods A meta-analysis assessed 14 studies—a total of 9012 patients with acute IS or TIA—comparing dual versus mono antiplatelet therapy. The CHANCE trial contributed 5170 patients (57.4% of total patients). Aspirin plus clopidogrel versus aspirin was assessed in five trials in 5901 patients, aspirin plus clopidogrel versus clopidogrel in 491 patients, aspirin plus dipyridamole versus aspirin in 964 patients, aspirin plus dipyridamole versus dipyridamole in 220 patients, aspirin plus dipyridamole versus clopidogrel in 1360 patients and cilostazol plus aspirin versus aspirin in 76 patients. Twelve studies were included from a previous meta-analysis plus the CHANCE trial and one other study of
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Evid Based Med June 2014 | volume 19 | number 3 |
Meta-analyses tend to overestimate efficacy of therapy because negative studies are less likely published. The present meta-analysis has numerous limitations: the study focused strongly on the CHANCE study, which provided 57.4% of the total patients; the studies varied in study populations, stroke severity, antiplatelet drugs used, onset to time of treatment, follow-up durations and other variables; finally, in some studies, only a small portion of patients were treated within 3 days of IS or TIA. Confounders might be different between patients treated with dual versus mono antiplatelet therapy in these patients. Propensity analyses need to be performed in these studies. CHANCE first investigated dual versus mono antiplatelet therapy before assessing different mono antiplatelet therapies. We do not know the extent to which clopidogrel monotherapy use from days 21 to 90 (following 21 days of dual clopidogrel plus aspirin therapy) affected difference in outcomes compared with 3 months of aspirin monotherapy. Results of ongoing clinical trials will provide more data on the efficacy and risks of dual and mono antiplatelet therapy. Until these data are available, aspirin monotherapy as currently recommended should be favoured for treatment of acute IS or TIA. If a patient develops a new IS or TIA while being treated with aspirin, use of mono clopidogrel therapy should be favoured. Competing interests None. References 1. National Collaborating Centre for Chronic Conditions (UK). National clinical guide for diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). National Institute for Health and Care Excellence (NICE) Clinical Guidelines, 2008. 2. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369:11–19. 3. Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008;359:1238–51. 4. Bath PM, Cotton D, Martin RH, et al. Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PROFESS subgroup analysis. Stroke 2010;41:732–8. 5. Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomized, double-blind, placebo-controlled trial. Lancet 2004;364:331–7.
