Avi Shimony

Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation

New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.

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.

Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism: direct and adjusted indirect meta-analysis of randomised controlled trials

Objective To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism. Design Systematic review and random effects meta-analysis. Data were extracted independently by two investigators. An adjusted indirect comparison was performed to compare between novel oral anticoagulants. Data sources Medline, Embase, and Cochrane Library (from inception to April 2012). Hand searching of relevant scientific works and contact with experts. Study selection Randomised controlled trials of novel oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism. Selected outcomes were recurrent events, major bleeding, and all cause mortality. Results Nine studies met our inclusion criteria, involving 16 701 patients evaluated for efficacy and 16 611 for safety. Data were stratified according to different novel oral anticoagulants. For recurrent acute venous thromboembolism, there were no significant differences in events rates between any of the anticoagulants and conventional treatment (rivaroxaban (four studies): relative risk 0.85, 95% confidence interval 0.55 to 1.31; dabigatran (two studies): 1.09, 0.76 to 1.57; ximelagatran (two studies): 1.06, 0.62 to 1.80; and apixaban (one study): 0.98, 0.20 to 4.79). Rivaroxaban reduced the risk of major bleeding compared with conventional treatment (0.57, 0.39 to 0.84), whereas other novel oral anticoagulants did not (0.76 (0.49 to 1.18) for dabigatran; 0.54 (0.28 to 1.03) for ximelagatran; 2.95 (0.12 to 71.82) for apixaban). For all cause mortality there were no significant differences between the novel oral anticoagulants and conventional treatment (0.96 (0.72 to 1.27) for rivaroxaban; 1.00 (0.67 to 1.50) for dabigatran; 0.67 (0.42 to 1.08) for ximelagatran; 6.89 (0.36 to 132.06) for apixaban). The adjusted indirect comparison between rivaroxaban and dabigatran did not show superiority of either drug over the others for major bleeding (0.75, 0.41 to 1.34) or the other endpoints. Conclusions Compared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding.

Meta-analysis of ten trials on the effectiveness of the radial versus the femoral approach in primary percutaneous coronary intervention.

The radial approach in primary percutaneous coronary intervention (PCI) has been recently assessed in both randomized and observational studies. However, observational studies have several biases that favor the radial approach. We conducted a meta-analysis of randomized controlled trials to compare the clinical outcomes of radial and femoral approach in primary PCI for ST-segment elevation myocardial infarction. The outcomes of interest included death, major bleeding, vascular complications/hematoma, and procedure time. The data were pooled using random-effects models. Ten randomized controlled trials involving 3,347 patients met our inclusion criteria. The radial approach was associated with improved survival (odds ratio 0.53, 95% confidence interval 0.33-0.84) and reduced vascular complications/hematoma (odds ratio 0.35, 95% confidence interval 0.24-0.53). A nonsignificant trend was found toward reduced major bleeding with the radial approach (odds ratio 0.63, 95% confidence interval 0.35-1.12). The procedural time with the radial approach was longer by < 2 minutes (mean difference 1.76 minutes, 95% confidence interval 0.59-2.92). In conclusion, in patients undergoing primary PCI, the radial approach is associated with lower short-term mortality. When feasible, the radial approach should be the favored route in primary PCI.

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.

Meta-Analysis of Monotherapy Versus Combination Therapy for Pulmonary Arterial Hypertension

Previous studies comparing combination therapy (CT) of pulmonary vasodilators to monotherapy (MT) in patients with pulmonary arterial hypertension (PAH) report conflicting results as to whether CT is more efficacious than MT. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials comparing CT to MT for patients with PAH. Data were pooled using the DerSimonian-Laird random-effects model. Six randomized controlled trials including 729 patients met our inclusion criteria. Follow-up ranged from 12 to 16 weeks. Compared to MT, CT resulted in a modest increase in 6-minute walk distance at the end of follow-up (weighted mean difference 25.2 m, 95% confidence interval [CI] 13.3 to 37.2). CT did not decrease mortality (risk ratio [RR] 0.42, 95% CI 0.08 to 2.25), admissions for worsening PAH (RR 0.72, 95% CI 0.36 to 1.44), or escalation of therapy (RR 0.36, 95% CI 0.09 to 1.39) and did not improve New York Heart Association functional class (RR 1.32, 95% CI 0.38 to 4.5) compared to MT. Incidence of study-drug discontinuation was similar between groups (RR 0.89, 95% CI 0.53 to 1.48). CT did not decrease the combined end point of mortality, admission for worsening PAH, lung transplantation, or escalation of PAH therapy (RR 0.42, 95% CI 0.17 to 1.04). In conclusion, this meta-analysis suggests that in PAH CT does not offer an advantage over MT apart from modestly increasing exercise capacity. However, given the paucity of good-quality data, more studies are required to define the efficacy of CT in this population before establishing final guidelines.

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.

Sex-related differences in access to care among patients with premature acute coronary syndrome

Background: Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care. Methods: We studied 1123 patients (18–55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures. Results: Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non–ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework. Interpretation: Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.

Meta-analysis of randomized controlled trials of intracoronary versus intravenous administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention for acute coronary syndrome.

It is unclear whether intracoronary (IC) bolus administration of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes is superior to intravenous (IV) administration. We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of IC and IV administrations of GPIs in patients with acute coronary syndromes. We systematically searched the Cochrane Library, EMBASE, and MEDLINE databases for RCTs comparing IC to IV administration of GPIs (abciximab, eptifibatide, tirofiban) during PCI. Data were pooled and stratified into short (1 month to 3 months) and mid-/long-term (≥6 months) follow-up durations. Ten RCTs involving 1,590 patients met our inclusion criteria. Compared to the IV group the IC group was more likely to have complete perfusion (Thrombolysis In Myocardial Infarction grade 3 flow) after PCI (risk ratio [RR] 1.08, 95% confidence interval [CI] 1.02 to 1.15). IC administration was associated with similar bleeding rates as IV (RR 0.92, 95% CI 0.68 to 1.24) but with a significant decrease in short-term target vessel revascularization (RR 0.54, 95% CI 0.30 to 0.96). IC administration was also associated with a significant decrease in short-term mortality (RR 0.45, 95% CI 0.23 to 0.90) but this decrease was no longer significant in mid-/long-term RCTs. In conclusion, compared to IV administration IC administration of GPIs has favorable effects on Thrombolysis In Myocardial Infarction flow, target vessel revascularization, and short-term mortality after PCI, with no difference in rates of bleeding. Data regarding mid-/long-term outcomes were limited and inconclusive. Large RCTs with longer follow-up are required to determine long-term safety and efficacy.

Incidence and Significance of Pericardial Effusion in Patients With Pulmonary Arterial Hypertension

BACKGROUND The incidence of pericardial effusion (PEF) during long-term follow-up among patients with pulmonary arterial hypertension (PAH) is unknown. We aimed to determine the incidence and prognostic significance of developing a new PEF among PAH patients. METHODS Records of consecutive patients diagnosed with PAH between January 1990 and May 2010 were reviewed. Patients had systematically undergone right heart catheterization, transthoracic echocardiography, and coronary angiography during their initial assessment as well as routine echocardiograms during follow-up. Effusions were graded as small (echo-free space in diastole <10 mm), moderate (10-20 mm), or large (≥ 20 mm). RESULTS The entire cohort consisted of 154 patients. The prevalence of identified PEF during initial assessment was 28.6%. The incidence of PEF among patients with no effusions who had additional echocardiographic studies during follow-up (n = 102) was 44.1%. Patients who developed PEF during follow-up had no differences with respect to baseline characteristics, associated aetiologies, hemodynamic parameters, and extent of coronary disease. Among these 102 patients, survival estimates were 94.9%, 75.0%, and 62.4% at 1, 3, and 5 years, respectively. Development of a PEF that was at least moderate-sized at its first appearance was a predictor of mortality in univariate (hazard ratio, 6.85; 95% confidence interval, 2.60-18.10) as well as multivariate analysis (hazard ratio, 3.95; 95% confidence interval, 1.26-12.40). CONCLUSIONS PEF develops frequently in PAH patients. In patients with no PEF at baseline, the appearance of a new moderate-size or larger PEF is associated with increased mortality, whereas no significantly increased mortality was observed when a small PEF develops.