Frailty and adverse outcomes in older adults being discharged from the emergency department: A prospective cohort study.

BACKGROUND: A growing number of frail older adults are treated in the emergency department (ED) and discharged home. There is an unmet need to identify older adults that are predisposed to functional decline and repeat ED visits so as to target them with proactive interventions. METHODS: A prospective cohort study was conducted in patients 75 years or older who were being discharged from the ED. The objective was to test the value of frailty screening tests, namely 5-meter gait speed and handgrip strength, to predict repeat ED visits at 1 and 6 months and functional decline at 1 month using multivariable logistic regression. RESULTS: After excluding 7 patients lost to follow-up, 150 patients were available for analysis. The mean age was 81.1 ± 4.9 years with 51% females, 13% arriving by ambulance, and 67% having at least two comorbid conditions. At ED discharge, 41% of patients were found to have slow gait speed, whereas 23% had weak handgrip strength. After adjustment, only slow gait speed was independently associated with functional decline at 1 month (odds ratio [OR] 1.39 per 0.1 meters/second decrement, 95% confidence interval [CI], 1.12 to 1.72) and repeat ED visits at 6 months (OR 1.20 per 0.1 meters/second decrement, 95% CI, 1.01 to 1.42). CONCLUSIONS: Gait speed can be feasibly measured at the time of ED discharge to identify frail older adults at risk for early functional decline and subsequent return to the ED. Conversely, grip strength was not found to be associated with functional decline or ED visits.

Defining optimal activated clotting time for percutaneous coronary intervention: A systematic review and Bayesian meta-regression.

BACKGROUND: Guidelines recommend routine monitoring of unfractionated heparin (UFH) with activated clotting time (ACT) during percutaneous coronary intervention (PCI). However, the optimal ACT for patients undergoing PCI is unclear. METHODS: We sought to determine the association of peak ACT during PCI with 30-day major adverse cardiac events (MACE; all-cause mortality, myocardial infarction, and revascularization) and bleeding events. We searched the Cochrane Central Register of Controlled Trials, EMBASE, and Medline for randomized controlled trials (RCTs) evaluating UFH through May 2015. Only patients randomized to UFH alone or to UFH with a glycoprotein IIb/IIIa inhibitor (GPI) were analyzed using Bayesian meta-regression. RESULTS: Among 13 included RCTs (n = 17455), eight (n = 5521) included study arms of UFH alone and 12 (n = 11934) included arms of UFH with a GPI. Peak ACT ranged from 201 to 460 sec for UFH alone and 248-317 sec for UFH with a GPI. With UFH alone, the probability of MACE was 7.0% (95% credible interval [CrI] 1.5, 31.5) for a peak ACT of 200 sec and 5.8% (95% CrI 2.6, 12.0) for 300 sec. Among UFH with a GPI, the probability of MACE was 2.8% (95% CrI 0.8, 6.8) for a peak ACT of 200 sec and 7.2% (95% CrI 5.4, 9.7) for 300 sec. CONCLUSION: Among individual RCTs, the probability of MACE and major bleeding events associated with low versus high values of peak ACT is inconsistent. Our meta-regression results are inconclusive, emphasizing the need for RCTs comparing low versus high doses of UFH. © 2016 Wiley Periodicals, Inc.

Effect of Fixed-Bolus (5,000 Units) Unfractionated Heparin Before Primary Percutaneous Coronary Intervention on Activated Clotting Time, Time Flow, and All-Cause Mortality.

The American College of Cardiology Foundation /American Heart Association guidelines recommend a weight-based dose of unfractionated heparin (UFH) for primary percutaneous coronary intervention (PCI). However, it is convention to administer a fixed-bolus dose of 5,000 units of UFH. It is unclear if 5,000 units are sufficient to achieve a therapeutic first activated clotting time (ACT). We conducted a retrospective cohort study to determine the proportion of therapeutic first ACT in patients who received 5,000 units of UFH before primary PCI. We examined the association of therapeutic first ACT with clinical outcomes, including post-PCI Thombolysis in Myocardial Infarction (TIMI) grade flow, myocardial infarction, bleeding, and mortality. Among the 269 included patients, 74.7% were men, and 61.4% were overweight or obese. The mean first ACT was 243.4 (SD = 61.5) seconds. Most patients (56.1%) had an infratherapeutic first ACT, 21.9% had a therapeutic first ACT, and 21.9% had a supratherapeutic first ACT. Furthermore, 44.6% of patients who achieved the American College of Cardiology Foundation/American Heart Association target weight-based dosing had an infratherapeutic ACT. The proportion of patients with post-PCI TIMI grade flow 0 to 2 was 14.6% among those with a first ACT that was infratherapeutic versus 6.8% among those with a first ACT that was not infratherapeutic (relative risk 2.15, 95% CI 0.99 to 4.65). In conclusion, over half of patients with ST-elevation myocardial infarction administered 5,000 units of UFH have an infratherapeutic first ACT and the high rate of poor TIMI grade flow in patients with an infratherapeutic ACT is concerning.

Icatibant Compared to Steroids and Antihistamines for ACE-Inhibitor-Induced Angioedema.

Article chosen Bas M, Greve J, Stelter K, et al. A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema. N Engl J Med 2015;372:418-25. doi:10.1056/NEJMoa1312524.

A National Survey of Mentoring Practices for Young Investigators in Circulatory and Respiratory Health.

Background. Improving mentorship may help decrease the shortage of young investigators (graduate students, postdoctoral fellows, and new investigators) available to work as independent researchers in cardiovascular and respiratory health. Objectives. To determine (1) the mentoring practices for trainees affiliated with the Canadian Institutes of Health Research (CIHR), Institute of Circulatory and Respiratory Health (ICRH), (2) the positive attributes of mentors, and (3) the recommendations regarding what makes good mentorship. Methods. We conducted a survey and descriptive analysis of young investigators with a CIHR Training and Salary Award from 2010 to 2013 or who submitted an abstract to the ICRH 2014 Young Investigators Forum. Clinicians were compared to nonclinicians. Results. Of 172 participants, 7.0% had no mentor. Only 43.6% had defined goals and 40.7% had defined timelines, while 54.1% had informal forms of mentorship. A significant proportion (33.1%) felt that their current mentorship did not meet their needs. Among clinicians, 22.2% would not have chosen the same mentor again versus 11.4% of nonclinicians. All participants favored mentors who provided guidance on career and work-life balance. Suggestions for improved mentoring included formal mentorship, increased networking, and quality assurance. Conclusion. There is an important need to improve mentoring in cardiovascular and respiratory health.

Should family members witness cardiopulmonary resuscitation?

CLINICAL QUESTION: What is the effect of family presence during cardiopulmonary resuscitation on family members and the medical team? ARTICLE CHOSEN: Jabre P, Belpomme V, Azoulay E, et al. Family presence during cardiopulmonary resuscitation. N Engl J Med 2013;368:1008-18. OBJECTIVE: The authors sought to determine whether systematically offering relatives the option to be present during cardiopulmonary resuscitation increases the proportion of relatives with posttraumatic stress disorder-related symptoms after 90 days. Secondary outcomes included the presence of anxiety and depression symptoms in relatives, the effect of family presence on medical efforts at resuscitation, the well-being of the medical team, and the occurrence of medicolegal claims.

Alternative smoking cessation aids: a meta-analysis of randomized controlled trials.

BACKGROUND: Acupuncture, hypnotherapy, and aversive smoking are the most frequently studied alternative smoking cessation aids. These aids are often used as alternatives to pharmacotherapies for smoking cessation; however, their efficacy is unclear. METHODS: We carried out a random effect meta-analysis of randomized controlled trials to determine the efficacy of alternative smoking cessation aids. We systematically searched the Cochrane Library, EMBASE, Medline, and PsycINFO databases through December 2010. We only included trials that reported cessation outcomes as point prevalence or continuous abstinence at 6 or 12 months. RESULTS: Fourteen trials were identified; 6 investigated acupuncture (823 patients); 4 investigated hypnotherapy (273 patients); and 4 investigated aversive smoking (99 patients). The estimated mean treatment effects were acupuncture (odds ratio [OR], 3.53; 95% confidence interval [CI], 1.03-12.07), hypnotherapy (OR, 4.55; 95% CI, 0.98-21.01), and aversive smoking (OR, 4.26; 95% CI, 1.26-14.38). CONCLUSION: Our results suggest that acupuncture and hypnotherapy may help smokers quit. Aversive smoking also may help smokers quit; however, there are no recent trials investigating this intervention. More evidence is needed to determine whether alternative interventions are as efficacious as pharmacotherapies.

Addition of frailty and disability to cardiac surgery risk scores identifies elderly patients at high risk of mortality or major morbidity.

Background- Cardiac surgery risk scores perform poorly in elderly patients, in part because they do not take into account frailty and disability which are critical determinants of health status with advanced age. There is an unmet need to combine established cardiac surgery risk scores with measures of frailty and disability to provide a more complete model for risk prediction in elderly patients undergoing cardiac surgery. Methods and Results- This was a prospective, multicenter cohort study of elderly patients (≥70 years) undergoing coronary artery bypass and/or valve surgery in the United States and Canada. Four different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores were measured in all patients. The primary outcome was the STS composite end point of in-hospital postoperative mortality or major morbidity. A total of 152 patients were enrolled, with a mean age of 75.9±4.4 years and 34% women. Depending on the scale used, 20-46% of patients were found to be frail, and 5-76% were found to have at least 1 disability. The most predictive scale in each domain was: 5-meter gait speed ≥6 seconds as a measure of frailty (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.17-5.90), ≥3 impairments in the Nagi scale as a measure of disability (OR, 2.98; 95% CI, 1.35-6.56) and either the Parsonnet score (OR, 1.08; 95% CI, 1.04-1.13) or Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI, 1.01-1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or STS-PROMM alone, (area under the curve, 0.68-0.72), addition of frailty and disability provided incremental value and improved model discrimination (area under the curve, 0.73-0.76). Conclusions- Clinicians should use an integrative approach combining frailty, disability, and risk scores to better characterize elderly patients referred for cardiac surgery and identify those that are at increased risk.

The cardiovascular effects of peroxisome proliferator-activated receptor agonists.

Although peroxisome proliferator-activated receptor agonists are prescribed to improve cardiovascular risk factors, their cardiovascular safety is controversial. We therefore reviewed the literature to identify landmark randomized controlled trials evaluating the effect of peroxisome proliferator-activated receptor gamma agonists (pioglitazone and rosiglitazone), alpha agonists (fenofibrate and gemfibrozil), and pan agonists (bezafibrate, muraglitazar, ragaglitazar, tesaglitazar, and aleglitazar) on cardiovascular outcomes. Pioglitazone may modestly reduce cardiovascular events but also may increase the risk of bladder cancer. Rosiglitazone increases the risk of myocardial infarction and has been withdrawn in European and restricted in the United States. Fibrates improve cardiovascular outcomes only in select subgroups: fenofibrate in diabetic patients with metabolic syndrome, gemfibrozil in patients with dyslipidemia, and bezafibrate in patients with diabetes or metabolic syndrome. The cardiovascular safety of the new pan agonist aleglitazar, currently in phase II trials, remains to be determined. The heterogenous effects of peroxisome proliferator-activated receptor agonists to date highlight the importance of postmarketing surveillance. The critical question of why peroxisome proliferator-activated receptor agonists seem to improve cardiovascular risk factors without significantly improving cardiovascular outcomes requires further investigation.

Safety of laparoscopic vs open bariatric surgery: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the risk of reoperation, wound infection, incisional hernia, anastomotic leak, and all-cause mortality associated with laparoscopic vs open bariatric surgery at a minimum of 12 months' follow-up. DATA SOURCES: We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases through June 1, 2010, for randomized controlled trials comparing laparoscopic with open bariatric surgery. STUDY SELECTION: We included all randomized controlled trials that reported weight loss outcomes and complications at a minimum of 12 months' follow-up and had a minimum of 50 patients. We identified 6 randomized controlled trials, which randomized 510 patients. DATA EXTRACTION: Data were extracted by 2 reviewers on study design, baseline characteristics, and surgical procedure. The outcome data extracted included change in weight and body mass index and the incidence of reoperation, wound infection, incisional hernia, anastomotic leak, and all-cause mortality. DATA SYNTHESIS: We used random-effects models, which accounted for within-study and between-study variability, to estimate pooled risk ratios (95% CIs). Compared with open surgery, laparoscopic surgery was associated with lower risk of wound infection (relative risk [RR], 0.21; 95% CI, 0.07-0.65) and incisional hernia (RR, 0.11; 95% CI, 0.03-0.35). The risk of reoperation (RR, 1.06; 95% CI, 0.70-1.61), anastomotic leak (RR, 0.64; 95% CI, 0.14-2.95), and all-cause mortality (RR, 0.86; 95% CI, 0.22-3.28) may be similar for laparoscopic and open bariatric surgery. CONCLUSION: Laparoscopic surgery may be a safer treatment than open surgery for patients requiring bariatric surgery.

Coronary artery perforation during percutaneous coronary intervention: a systematic review and meta-analysis.

Numerous studies have examined the incidence, predictors, outcomes, and management strategies of coronary artery perforation (CAP). Individually, these studies have been inconclusive because of their limited sample sizes and/or single-centre designs. We conducted a systematic review and meta-analysis of studies pertaining to CAP in order to estimate its incidence and outcomes and to critically review its risk factors and treatment. We systematically searched the literature to identify all registry studies investigating CAP. Data were pooled by means of the random-effects model. In 16 studies involving 197,061 percutaneous coronary interventions, the pooled incidence of CAP was 0.43% (95% confidence interval, 0.35%-0.52%). The most reproducible risk factors were treatment of complex lesions and use of atheroablative devices. A variety of major management strategies for CAP were used, in particular, observation, heparin reversal, prolonged balloon inflation, covered stent implantation, pericardiocentesis, and surgery. In a hierarchical Bayesian random-effects model, the pooled tamponade rates were 0.4% (95% credible interval [CrI], 0.0%-5.7%), 3.3% (95% CrI, 0.0%-11.4%), and 45.7% (95% CrI, 34.9%-57.5%) for patients with Ellis class I, II, and III CAP, respectively. Pooled mortality rates were 0.3% (95% CrI, 0.0%-4.4%), 0.4% (95% CrI, 0.0%-2.8%), and 21.2% (95% CrI, 12.0%-31.4%) for patients with Ellis class I, II, and III CAP respectively. CAP complicating percutaneous coronary intervention is rare, and its morbidity and mortality vary directly with Ellis classification. Management discrepancies highlight the need to establish a uniform treatment paradigm for CAP.

Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Aerobic exercise is a common nonpharmacological intervention for the management of obesity. However, the efficacy of isolated aerobic exercise at promoting weight loss is unclear. We conducted a systematic review and meta-analysis to evaluate the efficacy of isolated aerobic exercise programs in overweight and obese populations. METHODS: We searched for published randomized controlled trial reports of aerobic exercise through January 20, 2010. Trials with an isolated aerobic exercise intervention were included. A random-effect model was used to synthesize the results of each intervention. RESULTS: We identified 14 trials involving 1847 patients. The duration of aerobic exercise programs ranged from 12 weeks to 12 months. Results were pooled for programs with 6-month duration and programs with 12-month duration. Six-month programs were associated with a modest reduction in weight (weighted mean difference [WMD]=-1.6 kg; 95% confidence interval [CI], -1.64 to -1.56) and waist circumference (WMD=-2.12 cm; 95% CI, -2.81 to -1.44). Twelve-month programs also were associated with modest reductions in weight (WMD=-1.7 kg; 95% CI, -2.29 to -1.11) and waist circumference (WMD=-1.95 cm; 95% CI, -3.62 to -0.29). CONCLUSION: Moderate-intensity aerobic exercise programs of 6-12 months induce a modest reduction in weight and waist circumference in overweight and obese populations. Our results show that isolated aerobic exercise is not an effective weight loss therapy in these patients. Isolated aerobic exercise provides modest benefits to blood pressure and lipid levels and may still be an effective weight loss therapy in conjunction with diets.

Therapeutic hypothermia in acute myocardial infarction: a systematic review.

Therapeutic hypothermia preserves neurologic function in post-cardiac arrest patients. Several studies suggest that hypothermia may preserve myocardial function in patients with acute myocardial infarction (AMI). We carried out a systematic review to evaluate the efficacy of therapeutic hypothermia at reducing infarct size and decreasing major adverse cardiac events (MACEs) and all-cause mortality in AMI patients. We searched ClinicalTrials.gov, the Cochrane Clinical Trials Register, EMBASE, and MEDLINE through July 2010 for studies investigating therapeutic hypothermia in AMI patients. Data were extracted by 2 reviewers. We identified 5 studies (693 patients), 2 of which were feasibility trials and 3 of which were randomized controlled trials (RCTs). Feasibility trials showed that therapeutic hypothermia is a safe and feasible intervention. RCTs showed that cardiac outcomes were similar at 30 days' follow-up for the hypothermia and control groups. Mean infarct size ranged from 2.0% to 14.1% of the left ventricle in the hypothermia group and from 8.0% to 13.8% of the left ventricle in the control group. MACEs ranged from 0.0% to 6.2% in the hypothermia group and 3.9% to 10.0% in the control group. All-cause mortality ranged from 0.0% to 3.4% and 2.2% to 10.0% in the hypothermia and control groups, respectively. Subgroup analyses suggested that hypothermia may reduce infarct size in patients with anterior wall infarction. Our review suggests that therapeutic hypothermia is safe and feasible. However, more evidence is needed to determine whether therapeutic hypothermia is associated with improved infarct size, MACEs, or all-cause mortality in RCTs of AMI patients.

Meta-analysis of usefulness of d-dimer to diagnose acute aortic dissection.

Numerous studies have examined whether plasma D-dimer (DD) can be used to identify patients with acute aortic dissection (AAD). These studies have been inconclusive because of their limited sample sizes and the different cut-off values employed. We aimed to conduct a systematic review and meta-analysis to examine the utility of plasma DD as a screening tool for AAD. We systematically searched EMBASE and MEDLINE and hand-searched relevant articles to identify studies investigating plasma DD as a screening tool for AAD. A value of 500 ng/ml was defined as the threshold for a positive plasma DD finding because it is widely used for ruling out pulmonary emboli. Using DerSimonian-Laird random-effects models we pooled data across studies to estimate sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (LRs). We identified 7 studies involving 298 subjects with AAD and 436 without. When data were pooled across studies, sensitivity (0.97, 95% confidence interval [CI] 0.94 to 0.99) and negative predictive value (0.96, 95% CI 0.93 to 0.98) were high. Specificity (0.56, 95% CI 0.51 to 0.60) and positive predictive value (0.60, 95% CI 0.55 to 0.66) were low. Negative LR showed an excellent discriminative ability (0.06, 95% CI 0.03 to 0.12), whereas positive LR did not (2.43, 95% CI 1.89 to 3.12). In conclusion, our meta-analysis suggests that plasma DD <500 ng/ml is a useful screening tool to identify patients who do not have AAD. Plasma DD may thus be used to identify subjects who are unlikely to benefit from further aortic imaging.

The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis.

OBJECTIVES: We sought to conduct a systematic review and meta-analysis of the cardiovascular risk associated with the metabolic syndrome as defined by the 2001 National Cholesterol Education Program (NCEP) and 2004 revised National Cholesterol Education Program (rNCEP) definitions. BACKGROUND: Numerous studies have investigated the cardiovascular risk associated with the NCEP and rNCEP definitions of the metabolic syndrome. There is debate regarding the prognostic significance of the metabolic syndrome for cardiovascular outcomes. METHODS: We searched the Cochrane Library, EMBASE, and Medline databases through June 2009 for prospective observational studies investigating the cardiovascular effects of the metabolic syndrome. Two reviewers extracted data, which were aggregated using random-effects models. RESULTS: We identified 87 studies, which included 951,083 patients (NCEP: 63 studies, 497,651 patients; rNCEP: 33 studies, 453,432 patients). There was little variation between the cardiovascular risk associated with NCEP and rNCEP definitions. When both definitions were pooled, the metabolic syndrome was associated with an increased risk of cardiovascular disease (CVD) (relative risk [RR]: 2.35; 95% confidence interval [CI]: 2.02 to 2.73), CVD mortality (RR: 2.40; 95% CI: 1.87 to 3.08), all-cause mortality (RR: 1.58; 95% CI: 1.39 to 1.78), myocardial infarction (RR: 1.99; 95% CI: 1.61 to 2.46), and stroke (RR: 2.27; 95% CI: 1.80 to 2.85). Patients with the metabolic syndrome, but without diabetes, maintained a high cardiovascular risk. CONCLUSIONS: The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality. Studies are needed to investigate whether or not the prognostic significance of the metabolic syndrome exceeds the risk associated with the sum of its individual components. Furthermore, studies are needed to elucidate the mechanisms by which the metabolic syndrome increases cardiovascular risk.

Behavioural interventions for smoking cessation: a meta-analysis of randomized controlled trials.

AIMS: Widely varying estimates of treatment effects have been reported in randomized controlled trials (RCTs) investigating the efficacy of behavioural interventions for smoking cessation. Previous meta-analyses investigating behavioural interventions have important limitations and do not include recently published RCTs. We undertook a meta-analysis of RCTs to synthesize the treatment effects of four behavioural interventions, including minimal clinical intervention (brief advice from a healthcare worker), and intensive interventions, including individual, group, and telephone counselling. METHODS AND RESULTS: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline, and PsycINFO databases. We included only RCTs that reported biochemically validated smoking cessation outcomes at 6 and/or 12 months after the target quit date. Outcomes were aggregated using hierarchical Bayesian random-effects models. We identified 50 RCTs, which randomized n = 26 927 patients (minimal clinical intervention: 9 RCTs, n = 6456; individual counselling: 23 RCTs, n = 8646; group counselling: 12 RCTs, n = 3600; telephone counselling: 10 RCTs, n = 8225). The estimated mean treatment effects were minimal clinical intervention [odds ratio (OR) 1.50, 95% credible interval (CrI) 0.84-2.78], individual counselling (OR 1.49, 95% CrI 1.08-2.07), group counselling (OR 1.76, 95% CrI 1.11-2.93), and telephone counselling (OR 1.58, 95% CrI 1.15-2.29). CONCLUSION: Intensive behavioural interventions result in substantial increases in smoking abstinence compared with control. Although minimal clinical intervention may increase smoking abstinence, there is insufficient evidence to draw strong conclusions regarding its efficacy.

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials.

BACKGROUND: Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation. METHODS: We searched the US Centers for Disease Control and Prevention's Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention. RESULTS: We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13), bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR 1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09-4.08). INTERPRETATION: Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.