Balance of symptomatic pulmonary embolism and symptomatic intracerebral hemorrhage with low-dose anticoagulation in recent ischemic stroke: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The current consensus is that anticoagulation therapy has no role acutely in the management of ischemic stroke, although there is still debate for specific conditions, such as cerebral venous thrombosis and cervical dissection. In addition, anticoagulation is used in the prevention of venous thromboembolic events. We assess the balance between preventing symptomatic pulmonary embolism (sPE) and causing symptomatic intracerebral hemorrhage (sICH) in patients with recent stroke who were randomized to low-dose subcutaneous anticoagulation in trials. METHODS: We systematically searched the Cochrane Library, Medline, Embase, and Science Citation Index for prospective randomized controlled trials assessing the effect of heparin and other antithrombotic therapies in patients with acute/early ischemic stroke. Included trials had to record information on pulmonary embolism and sICH. Risk ratios (RRs) were calculated for sICH per sPE for each trial using a random effects model. RESULTS: We identified 15 trials of low-dose subcutaneous anticoagulation. The trials studied low molecular weight heparin, heparinoids, and unfractionated heparin. The ratio of sICH to sPE was increased with low molecular weight heparin (RR 2.1; 95% confidence interval [CI] 1.03-4.28), but was in approximated unity with heparinoids (RR 1.27; 95% CI 0.31-5.17) and unfractionated heparin (RR 0.99; 95% CI 0.65-1.52). CONCLUSIONS: Prophylactic/low-dose heparin increased sICH by more than they reduced sPE in patients with recent ischemic stroke. Therefore, their routine acute use cannot be recommended, but they may still be relevant in patients at very high risk of PE (eg, morbid obesity, previous venous thromboembolism, and inherited thrombophilia) or if started later, although trials have not assessed these issues.

Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Antiplatelets are recommended for patients with acute noncardioembolic stroke or transient ischemic attack. We compared the safety and efficacy of dual versus mono antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. METHODS: Completed randomized controlled trials of dual versus mono antiplatelet therapy in patients with acute (≤3 days) ischemic stroke/transient ischemic attack were identified using electronic bibliographic searches. The primary outcome was recurrent stroke (ischemic, hemorrhagic, unknown; fatal, nonfatal). Comparison of binary outcomes between treatment groups was analyzed with random effect models and described using risk ratios (95% CI). RESULTS: Twelve completed randomized trials involving 3766 patients were included. In comparison with mono antiplatelet therapy, dual therapy (aspirin+dipyridamole and aspirin+clopidogrel) significantly reduced stroke recurrence, dual 58 (3.3%) versus mono 91 (5.0%; risk ratio, 0.67; 95% CI, 0.49-0.93); composite vascular event (stroke, myocardial infarction, vascular death), dual 74 (4.4%) versus mono 106 (6%; risk ratio, 0.75; 95% CI, 0.56-0.99); and the combination of stroke, transient ischemic attack, acute coronary syndrome, and all death, dual 100 (1.7%) versus mono 136 (9.1%; risk ratio, 0.71; 95% CI, 0.56-0.91); dual therapy was also associated with a nonsignificant trend to increase major bleeding, dual 15 (0.9%) versus mono 6 (0.4%; risk ratio, 2.09; 95% CI, 0.86-5.06). CONCLUSIONS: Dual antiplatelet therapy appears to be safe and effective in reducing stroke recurrence and combined vascular events in patients with acute ischemic stroke or transient ischemic attack as compared with mono therapy. These results need to be tested in prospective studies.

Blood pressure reduction and cardiovascular prevention: meta-regression using ordered categorical (ordinal) event data.

BACKGROUND: Blood pressure (BP)-lowering trials studying efficacy mostly assesses binary outcome events, for example stroke/no stroke. Analysis of ordered categorical vascular events (e.g. three levels: fatal stroke/nonfatal stroke/no stroke) provides information on severity and is more powerful statistically than analyses using binary data, as used in previous meta-regression analyses of BP lowering. METHODS: Summary data on stroke, myocardial infarction, and combined vascular events were obtained from published BP-lowering trials. Ordinal and binary odds ratios were calculated. The relationship between the difference in BP and treatment odds ratio was assessed using meta-regression. RESULTS: Thirty-eight trials involving 180 804 patients were included. A 'U' or 'J'-shaped relationship was found between on-treatment BP difference and three level ordinal stroke, ordinal myocardial infarction, and ordinal combined vascular outcome. Similar relationships were noted for binary stroke, myocardial infarction, and combined vascular outcome. Meta-regression curves for three level ordinal analyses were similar in shape and position to that for binary analyses. CONCLUSIONS: Meta-regression using ordinal outcomes in hypertension trials is practical and gives comparable values for the odds ratio as found in analyses based on binary outcomes. However, trials and meta-analyses reporting ordinal outcomes provide additional information in particular that lowering BP reduces both the severity and frequency of fatal and recurrent stroke. Trials should report data so that ordinal analyses may be performed.