Sarah B. Windle

Electronic Cigarettes in North America History, Use, and Implications for Smoking Cessation

Background— Designed to mimic the look and feel of tobacco cigarettes, electronic cigarettes (e-cigarettes) may facilitate smoking cessation. However, the efficacy and safety of e-cigarette use for this purpose remain poorly understood. Our objectives were to review the available data on the efficacy and safety of e-cigarettes for smoking cessation and to consider issues relevant to the context in which they are used, including product awareness and regulatory and ethical concerns. Methods and Results— We systematically searched PubMed for randomized controlled trials and uncontrolled, experimental studies involving e-cigarettes. Included studies were limited to English or French language reports. Quality assessment was performed according to the Cochrane Risk of Bias tool. We identified 169 publications, of which 7 studies were included. Studies have concluded that e-cigarettes can help reduce the number of cigarettes smoked and may be as effective for smoking cessation as the nicotine patch. Although there is a lack of data concerning the safety and efficacy of e-cigarettes as a smoking cessation therapy, available evidence showed no significant difference in adverse event rates between e-cigarettes and the nicotine patch. E-cigarettes are widely used among smokers attempting to quit. However, significant international variation remains in the regulatory mechanisms governing the sale and distribution of e-cigarettes. Ethical concerns surround the use of e-cigarettes among minors and their potential to undermine efforts to reduce cigarette smoking. Conclusion— Given the limited available evidence on the risks and benefits of e-cigarette use, large, randomized, controlled trials are urgently needed to definitively establish their potential for smoking cessation.Background— Designed to mimic the look and feel of tobacco cigarettes, electronic cigarettes (e-cigarettes) may facilitate smoking cessation. However, the efficacy and safety of e-cigarette use for this purpose remain poorly understood. Our objectives were to review the available data on the efficacy and safety of e-cigarettes for smoking cessation and to consider issues relevant to the context in which they are used, including product awareness and regulatory and ethical concerns. Methods and Results— We systematically searched PubMed for randomized controlled trials and uncontrolled, experimental studies involving e-cigarettes. Included studies were limited to English or French language reports. Quality assessment was performed according to the Cochrane Risk of Bias tool. We identified 169 publications, of which 7 studies were included. Studies have concluded that e-cigarettes can help reduce the number of cigarettes smoked and may be as effective for smoking cessation as the nicotine patch. Although there is a lack of data concerning the safety and efficacy of e-cigarettes as a smoking cessation therapy, available evidence showed no significant difference in adverse event rates between e-cigarettes and the nicotine patch. E-cigarettes are widely used among smokers attempting to quit. However, significant international variation remains in the regulatory mechanisms governing the sale and distribution of e-cigarettes. Ethical concerns surround the use of e-cigarettes among minors and their potential to undermine efforts to reduce cigarette smoking. Conclusion— Given the limited available evidence on the risks and benefits of e-cigarette use, large, randomized, controlled trials are urgently needed to definitively establish their potential for smoking cessation. # CLINICAL PERSPECTIVE {#article-title-40}

Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome

Background— Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. Methods and Results— We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group (P=0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (P=0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively (P=0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). Conclusions— Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573.

Legislative approaches to tackling the obesity epidemic

Canada and other developed countries are facing an obesity epidemic, with a substantial rise in the prevalence of overweight and obesity among adults and children.[1][1]–[3][2] The 2007–2009 Canadian Health Measures Survey revealed that 37% of adults were overweight (body mass index [BMI] 25.0

Stent Retrievers for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-analysis of Randomized Clinical Trials

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.

Combination Therapies for Smoking Cessation: A Hierarchical Bayesian Meta-Analysis

CONTEXT Treatment guidelines recommend the use of combination therapies for smoking cessation, particularly behavioral therapy (BT) as an adjunct to pharmacotherapy. However, these guidelines rely on previous reviews with important limitations. This studys objective was to evaluate the efficacy of combination therapies compared with monotherapies, using the most rigorous data available. EVIDENCE ACQUISITION A systematic review and meta-analysis of RCTs of pharmacotherapies, BTs, or both were conducted. The Cochrane Library, Embase, PsycINFO, and PubMed databases were systematically searched from inception to July 2015. Inclusion was restricted to RCTs reporting biochemically validated abstinence at 12 months. Direct and indirect comparisons were made in 2015 between therapies using hierarchical Bayesian models. EVIDENCE SYNTHESIS The search identified 123 RCTs meeting inclusion criteria (60,774 participants), and data from 115 (57,851 participants) were meta-analyzed. Varenicline with BT increased abstinence more than other combinations of a pharmacotherapy with BT (varenicline versus bupropion: OR=1.56, 95% credible interval [CrI]=1.07, 2.34; varenicline versus nicotine patch: OR=1.65, 95% CrI=1.10, 2.51; varenicline versus short-acting nicotine-replacement therapies: OR=1.68, 95% CrI=1.15, 2.53). Adding BT to any pharmacotherapy compared with pharmacotherapy alone was inconclusive, owing to wide CrIs (OR=1.17, CrI=0.60, 2.12). Nicotine patch with short-acting nicotine-replacement therapy appears safe and increases abstinence versus nicotine-replacement monotherapy (OR=1.63, CrI=1.06, 3.03). Data are limited concerning other pharmacotherapy combinations and their safety and tolerability. CONCLUSIONS Evidence suggests that combination therapy benefits may be less than previously thought. Combined with BT, varenicline increases abstinence more than other pharmacotherapy with BT combinations.

Pharmacological management strategies for stroke prevention following transcatheter aortic valve replacement: A systematic review

BACKGROUND The most appropriate pharmacological treatment for stroke prevention after transcatheter aortic valve replacement (TAVR) is unclear. We performed a systematic review of randomized controlled trials (RCTs) and observational studies examining the effect of various pharmacological treatment regimens on rates of stroke, bleeding, and death after TAVR. METHODS We searched Cochrane Library, Embase, and Medline for RCTs and observational studies comparing ≥2 antithrombotic regimens in TAVR patients. Included antithrombotic regimens were defined as one or more antiplatelet agents (aspirin, clopidogrel, prasugrel, or ticagrelor) and/or anticoagulants (vitamin K antagonists or novel oral anticoagulants). RESULTS Eight studies (2 RCTs and 6 observational studies) met our inclusion criteria (n=1598). Rates of major stroke ranged from 0% to 5.6% with no detected differences between treatment arms. All-cause mortality ranged from 5% to 15%, and no differences in mortality were detected between therapies. A consistent pattern of reduction in major or life-threatening bleeding was found with a single antiplatelet therapy (SAPT) compared to dual antiplatelet therapy (DAPT). However, this difference only reached statistical significance in a single cohort study (risk ratio 0.24; 95% confidence interval 0.12, 0.46). No differences between anticoagulant therapies were detected for any endpoint. Overall, studies were underpowered to detect differences between treatment groups. CONCLUSION Similar rates of stroke, bleeding, and mortality were found among most studies. A trend towards reduced rates of major or life-threatening bleeding when comparing SAPT to DAPT was found. Numbers of events were small, highlighting the need for larger studies on which to base pharmacological recommendations post-TAVR.

A randomized controlled trial of the efficacy and safety of varenicline for smoking cessation after acute coronary syndrome: Design and methods of the Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome trial

UNLABELLED Patients who continue to smoke after an acute coronary syndrome (ACS) have a significantly increased risk of reinfarction and death compared with those who quit. Varenicline is a first-line smoking cessation therapy with proven efficacy in the general population. However, its efficacy and safety immediately after an ACS are unknown. METHODS The EVITA trial is a multicenter, double-blind, randomized, placebo-controlled trial (NCT00794573). The primary objective is to evaluate the efficacy of varenicline after ACS in achieving biochemically validated smoking abstinence at 24 weeks. The secondary objectives are to examine the efficacy of varenicline for smoking abstinence and reduction in daily cigarette consumption at 52 weeks and to describe the occurrence of adverse events. Three hundred and two patients motivated to quit smoking were enrolled in the United States and Canada from November 2009 to December 2014 while hospitalized with an ACS. These participants were randomized (1:1) to either varenicline (1.0 mg twice daily) or placebo for 12 weeks. The trial includes follow-ups by telephone at weeks 1, 2, and 8 and clinic visits at weeks 4, 12, 24, and 52. Data collected include demographic and clinical characteristics, self-reported smoking, exhaled carbon monoxide (an indicator of current smoking), and adverse events. CONCLUSION The EVITA trial will provide novel information concerning the efficacy and safety of varenicline immediately after ACS. If varenicline is efficacious in this population, it will have a major impact on secondary prevention of recurrent clinical events in patients post-ACS.

Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital

BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. METHODS: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. RESULTS: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI −0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI −3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI −7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference −0.7%, 95% CI −7.8% to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573

A Systematic Review of Combination Therapies for Smoking Cessation

Introduction: The use of pharmacological and behavioural therapies has been shown to help smokers quit. However, the efficacy of combining smoking cessation therapies remains poorly understood. We conducted a systematic review of randomized controlled trials (RCTs) with factorial designs to assess the efficacy of combination smoking cessation therapies. Methods: We performed a systematic search of the Cochrane Library, EMBASE, PsycINFO, and PubMed databases for RCTs of combination therapies for smoking cessation. We included RCTs with factorial designs,reporting biochemically validated point prevalence or continuous abstinence outcomes at 6 or 12 months. Combination therapies were either two pharmacotherapies or apharmacotherapy with behavioural therapy. Pharmacotherapies included nicotine replacement therapies (NRTs), bupropion, and varenicline. Behavioural therapies included counselling and minimal intervention. Results: A total of 11 RCTs met our inclusion criteria: 4 combinations of pharmacotherapies and 7 combinations of a pharmacotherapy with behavioural intervention. Combinations were two NRTs (2 RCTs), bupropion with NRT (3 RCTs), bupropion with behavioural intervention (4 RCTs), and NRT with behavioural intervention (3 RCTs). No identified trials combined varenicline with other included pharmacotherapies. Combining pharmacotherapies did not increase smoking abstinence at 6 or 12 months, compared with pharmacological monotherapies. Evidence suggests a modest yet inconsistent benefit from combining pharmacotherapy with behavioural therapy. Conclusion: Evidence from RCTs with factorial designs does not conclusively show combination smoking cessation therapies to be superior to monotherapies. Pharmacotherapies could be prescribed without behavioural therapy, with minimal loss of treatment efficacy. Key words: Smoking cessation, combination therapy, systematic review

Electronic Cigarettes in North AmericaCLINICAL PERSPECTIVE

Background— Designed to mimic the look and feel of tobacco cigarettes, electronic cigarettes (e-cigarettes) may facilitate smoking cessation. However, the efficacy and safety of e-cigarette use for this purpose remain poorly understood. Our objectives were to review the available data on the efficacy and safety of e-cigarettes for smoking cessation and to consider issues relevant to the context in which they are used, including product awareness and regulatory and ethical concerns. Methods and Results— We systematically searched PubMed for randomized controlled trials and uncontrolled, experimental studies involving e-cigarettes. Included studies were limited to English or French language reports. Quality assessment was performed according to the Cochrane Risk of Bias tool. We identified 169 publications, of which 7 studies were included. Studies have concluded that e-cigarettes can help reduce the number of cigarettes smoked and may be as effective for smoking cessation as the nicotine patch. Although there is a lack of data concerning the safety and efficacy of e-cigarettes as a smoking cessation therapy, available evidence showed no significant difference in adverse event rates between e-cigarettes and the nicotine patch. E-cigarettes are widely used among smokers attempting to quit. However, significant international variation remains in the regulatory mechanisms governing the sale and distribution of e-cigarettes. Ethical concerns surround the use of e-cigarettes among minors and their potential to undermine efforts to reduce cigarette smoking. Conclusion— Given the limited available evidence on the risks and benefits of e-cigarette use, large, randomized, controlled trials are urgently needed to definitively establish their potential for smoking cessation.Background— Designed to mimic the look and feel of tobacco cigarettes, electronic cigarettes (e-cigarettes) may facilitate smoking cessation. However, the efficacy and safety of e-cigarette use for this purpose remain poorly understood. Our objectives were to review the available data on the efficacy and safety of e-cigarettes for smoking cessation and to consider issues relevant to the context in which they are used, including product awareness and regulatory and ethical concerns. Methods and Results— We systematically searched PubMed for randomized controlled trials and uncontrolled, experimental studies involving e-cigarettes. Included studies were limited to English or French language reports. Quality assessment was performed according to the Cochrane Risk of Bias tool. We identified 169 publications, of which 7 studies were included. Studies have concluded that e-cigarettes can help reduce the number of cigarettes smoked and may be as effective for smoking cessation as the nicotine patch. Although there is a lack of data concerning the safety and efficacy of e-cigarettes as a smoking cessation therapy, available evidence showed no significant difference in adverse event rates between e-cigarettes and the nicotine patch. E-cigarettes are widely used among smokers attempting to quit. However, significant international variation remains in the regulatory mechanisms governing the sale and distribution of e-cigarettes. Ethical concerns surround the use of e-cigarettes among minors and their potential to undermine efforts to reduce cigarette smoking. Conclusion— Given the limited available evidence on the risks and benefits of e-cigarette use, large, randomized, controlled trials are urgently needed to definitively establish their potential for smoking cessation. # CLINICAL PERSPECTIVE {#article-title-40}