BackgroundVarenicline is an efficacious smoking‐cessation drug. However, previous meta‐analyses provide conflicting results regarding its cardiovascular safety. The publication of several new randomized controlled trials (RCTs) provides an opportunity to reassess this potential adverse drug reaction.Methods and ResultsWe searched MEDLINE, EMBASE, and the Cochrane Library for RCTs that compare varenicline with placebo for smoking cessation. RCTs reporting cardiovascular serious adverse events and/or all‐cause mortality during the treatment period or within 30 days of treatment discontinuation were eligible for inclusion. Relative risks (RRs) with 95% CIs were generated by using DerSimonian–Laird random‐effects models. Thirty‐eight RCTs met our inclusion criteria (N=12 706). Events were rare in both varenicline (57/7213) and placebo (43/5493) arms. No difference was observed for cardiovascular serious adverse events when comparing varenicline with placebo (RR 1.03, 95% CI 0.72–1.49). Similar findings were obtained when examining cardiovascular (RR 1.04, 95% CI 0.57–1.89) and noncardiovascular patients (RR 1.03, 95% CI 0.64–1.64). Deaths were rare in both varenicline (11/7213) and placebo (9/5493) arms. Although 95% CIs were wide, pooling of all‐cause mortality found no difference between groups (RR 0.88, 95% CI 0.50–1.52), including when stratified by participants with (RR 1.24, 95% CI 0.40–3.83) and without (RR 0.77, 95% CI 0.40–1.48) cardiovascular disease.ConclusionsWe found no evidence that varenicline increases the rate of cardiovascular serious adverse events. Results were similar among those with and without cardiovascular disease. Given varenicline's efficacy as a smoking cessation drug and the long‐term cardiovascular benefits of cessation, it should continue to be prescribed for smoking cessation.

IMPORTANCE Stent retrievers are a promising alternative for the treatment of acute ischemic stroke (AIS). Several recently completed clinical trials have examined the use of stent retrievers with intravenous recombinant tissue plasminogen activator (rtPA) compared with rtPA alone. OBJECTIVE To conduct a systematic review and meta-analysis of randomized clinical trials to quantify the benefits and risks of using stent retrievers in addition to rtPA for the treatment of AIS. DATA SOURCES The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials databases were searched from inception to July 2015 for the keywords stent*, retriev*, Solitaire, Trevo, Revive, and stroke. Trial registries were also searched. A total of 326 publications were identified and 213 potentially relevant records were screened. STUDY SELECTION Randomized clinical trials that examined stent retrievers with rtPA vs rtPA alone were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS Two independent reviewers extracted study data and performed quality assessment using the Cochrane Risk of Bias Tool. DerSimonian and Laird random-effects models were used to estimate relative risks (RRs), risk differences (RDs), and numbers needed to treat. MAIN OUTCOMES AND MEASURES The primary outcome was the proportion of patients achieving functional independence (defined as a score of 0-2 on the modified Rankin Scale, with 0 indicating no disability and 6 indicating death) at 90 days. Risks of all-cause mortality, intracranial hemorrhage, and parenchymal hematoma at 90 days were also assessed. RESULTS Five randomized clinical trials met our inclusion criteria (n = 1287 patients). Patients randomized to stent-retriever therapy with rtPA had significantly improved rates of functional independence at 90 days compared with those randomized to rtPA alone (RR, 1.72; 95% CI, 1.48-1.99; RD, 0.19; 95% CI, 0.13-0.25). When data were pooled across trials, the effect of stent-retriever therapy on all-cause mortality at 90 days was inconclusive (RR, 0.82; 95% CI, 0.60-1.11; RD, −0.04; 95% CI, −0.08 to 0.1). There were similarly no detectable differences in the risks of intracranial hemorrhage (RR, 1.15; 95% CI, 0.67-1.97; RD, 0.00; 95% CI, −0.02 to 0.03) or parenchymal hematoma (RR, 1.18; 95% CI, 0.71-1.94; RD, 0.01; 95% CI, −0.01 to 0.04), although the 95% CIs were wide. Fixed-effects sensitivity analyses produced similar results for all outcomes. CONCLUSIONS AND RELEVANCE The use of stent retrievers in conjunction with rtPA vs rtPA alone is associated with significant improvement of functional independence 90 days after AIS.

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