Mike Manchak, MD; Robert Holloway, MD, MPH
Does adding clopidogrel to aspirin reduce recurrence in patients with recent lacunar stroke?
2 x 2 factorial, randomized, placebo-controlled trial (Secondary Prevention of Small Subcortical Strokes [SPS3] trial). ClinicalTrials.gov NCT00059306.
Blinded* (patients, clinicians, and event adjudication committee).
Mean 3.4 years (antiplatelet component of the trial was stopped early for apparent futility and potential harm).
82 clinical centers in North America, Latin America, and Spain.
3020 patients ≥ 30 years of age (mean age 63 y, 63% men) who had symptomatic, magnetic resonance imaging (MRI)–confirmed lacunar stroke 14 to 180 days before randomization or transient lacunar ischemic attacks confirmed by diffusion-weighted MRI. Exclusion criteria included disabling stroke (modified Rankin score ≥ 4 out of 6); major risk factors for cardioembolic sources of stroke; ipsilateral carotid artery disease appropriate for surgery; subcortical infarction with diameter > 1.5 cm; MRI-confirmed recent or remote cortical infarction; and history of intracerebral hemorrhage other than microbleeding, intracranial hemorrhage other than traumatic hemorrhage, or cortical ischemic stroke.
Enteric-coated aspirin, 325 mg/d, plus clopidogrel, 75 mg/d (n = 1517), or aspirin plus matching placebo (n = 1503). Patients were also randomized to 1 of 2 systolic blood pressure targets (< 130 mm Hg or 130 to 149 mm Hg).
Recurrent stroke (ischemic stroke or intracranial hemorrhage including subdural hematoma). Other outcomes included major extracranial hemorrhage and all-cause mortality.
87% (intention-to-treat analysis).
Clopidogrel plus aspirin did not reduce recurrent stroke and increased major extracranial hemorrhage and all-cause mortality more than aspirin alone (Table).
In patients with recent lacunar stroke, adding clopidogrel to aspirin did not reduce recurrent stroke and increased major extracranial hemorrhage and all-cause mortality.
Aspirin plus clopidogrel vs aspirin plus placebo in patients with recent lacunar stroke†
†Abbreviations defined in Glossary. RRR, RRI, NNH, and CI calculated from hazard ratios and control event rates in article.
‡Ischemic stroke (6.6% vs 8.3%, P = 0.13), intracranial hemorrhage (1.4% vs 0.86%, P = 0.15), and unknown stroke type (0.26% vs 0.07%, P = 0.22).
Manchak M, Holloway R. Adding clopidogrel to aspirin did not reduce recurrent stroke and increased bleeding in lacunar stroke. Ann Intern Med. ;157:JC6–2. doi: 10.7326/0003-4819-157-12-201212180-02002
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Published: Ann Intern Med. 2012;157(12):JC6-2.
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