Saurav Chatterjee

Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis.

IMPORTANCE Thrombolytic therapy may be beneficial in the treatment of some patients with pulmonary embolism. To date, no analysis has had adequate statistical power to determine whether thrombolytic therapy is associated with improved survival, compared with conventional anticoagulation. OBJECTIVE To determine mortality benefits and bleeding risks associated with thrombolytic therapy compared with anticoagulation in acute pulmonary embolism, including the subset of hemodynamically stable patients with right ventricular dysfunction (intermediate-risk pulmonary embolism). DATA SOURCES PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from inception through April 10, 2014. STUDY SELECTION Eligible studies were randomized clinical trials comparing thrombolytic therapy vs anticoagulant therapy in pulmonary embolism patients. Sixteen trials comprising 2115 individuals were identified. Eight trials comprising 1775 patients specified inclusion of patients with intermediate-risk pulmonary embolism. DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted trial-level data including number of patients, patient characteristics, duration of follow-up, and outcomes. MAIN OUTCOMES AND MEASURES The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage (ICH). Peto odds ratio (OR) estimates and associated 95% CIs were calculated using a fixed-effects model. RESULTS Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89% [41/1054] with anticoagulants; number needed to treat [NNT] = 59) and greater risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1061] vs 3.42% [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1024] vs 0.19% [2/1019]; NNH = 78). Major bleeding was not significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50-3.14). Thrombolysis was associated with a lower risk of recurrent pulmonary embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT = 54). In intermediate-risk pulmonary embolism trials, thrombolysis was associated with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events (OR, 3.19; 95% CI, 2.07-4.92). CONCLUSIONS AND RELEVANCE Among patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH. However, findings may not apply to patients with pulmonary embolism who are hemodynamically stable without right ventricular dysfunction.

Association of Blood Transfusion With Increased Mortality in Myocardial Infarction: A Meta-analysis and Diversity-Adjusted Study Sequential Analysis

BACKGROUND The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists. METHODS A systematic search of studies published between January 1, 1966, and March 31, 2012, was conducted using MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. English-language studies comparing blood transfusion with no blood transfusion or a liberal vs restricted blood transfusion strategy were identified. Two study authors independently reviewed 729 originally identified titles and abstracts and selected 10 for analysis. Study title, follow-up period, blood transfusion strategy, and mortality outcomes were extracted manually from all selected studies, and the quality of each study was assessed using the strengthening Meta-analysis of Observational Studies in Epidemiology checklist. RESULTS Studies of blood transfusion strategy in anemia associated with myocardial infarction were abstracted, as well as all-cause mortality rates at the longest available follow-up periods for the individual studies. Pooled effect estimates were calculated with random-effects models. Analyses of blood transfusion in myocardial infarction revealed increased all-cause mortality associated with a strategy of blood transfusion vs no blood transfusion during myocardial infarction (18.2% vs 10.2%) (risk ratio, 2.91; 95% CI, 2.46-3.44; P < .001), with a weighted absolute risk increase of 12% and a number needed to harm of 8 (95% CI, 6-17). Multivariate meta-regression revealed that blood transfusion was associated with a higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (risk ratio, 2.04; 95% CI, 1.06-3.93; P = .03). CONCLUSIONS Blood transfusion or a liberal blood transfusion strategy compared with no blood transfusion or a restricted blood transfusion strategy is associated with higher all-cause mortality rates. A practice of routine or liberal blood transfusion in myocardial infarction should not be encouraged but requires investigation in a large trial with low risk for bias.

Impact of More Restrictive Blood Transfusion Strategies on Clinical Outcomes: A Meta-analysis and Systematic Review

BACKGROUND There is accumulating evidence that restricting blood transfusions improves outcomes, with newer trials showing greater benefit from more restrictive strategies. We systematically evaluated the impact of various transfusion triggers on clinical outcomes. METHODS The MEDLINE database was searched from 1966 to April 2013 to find randomized trials evaluating a restrictive hemoglobin transfusion trigger of <7 g/dL, compared with a more liberal trigger. Two investigators independently extracted data from the trials. Outcomes evaluated included mortality, acute coronary syndrome, pulmonary edema, infections, rebleeding, number of patients transfused, and units of blood transfused per patient. Extracted data also included information on study setting, design, participant characteristics, and risk for bias of the included trials. A secondary analysis evaluated trials using less restrictive transfusion triggers, and a systematic review of observational studies evaluated more restrictive triggers. RESULTS In the primary analysis, pooled results from 3 trials with 2364 participants showed that a restrictive hemoglobin transfusion trigger of <7 g/dL resulted in reduced in-hospital mortality (risk ratio [RR], 0.74; confidence interval [CI], 0.60-0.92), total mortality (RR, 0.80; CI, 0.65-0.98), rebleeding (RR, 0.64; CI, 0.45-0.90), acute coronary syndrome (RR, 0.44; CI, 0.22-0.89), pulmonary edema (RR, 0.48; CI, 0.33-0.72), and bacterial infections (RR, 0.86; CI, 0.73-1.00), compared with a more liberal strategy. The number needed to treat with a restrictive strategy to prevent 1 death was 33. Pooled data from randomized trials with less restrictive transfusion strategies showed no significant effect on outcomes. CONCLUSIONS In patients with critical illness or bleed, restricting blood transfusions by using a hemoglobin trigger of <7 g/dL significantly reduces cardiac events, rebleeding, bacterial infections, and total mortality. A less restrictive transfusion strategy was not effective.

Benefits of β blockers in patients with heart failure and reduced ejection fraction: network meta-analysis

Objective To clarify whether any particular β blocker is superior in patients with heart failure and reduced ejection fraction or whether the benefits of these agents are mainly due to a class effect. Design Systematic review and network meta-analysis of efficacy of different β blockers in heart failure. Data sources CINAHL(1982-2011), Cochrane Collaboration Central Register of Controlled Trials (-2011), Embase (1980-2011), Medline/PubMed (1966-2011), and Web of Science (1965-2011). Study selection Randomized trials comparing β blockers with other β blockers or other treatments. Data extraction The primary endpoint was all cause death at the longest available follow-up, assessed with odds ratios and Bayesian random effect 95% credible intervals, with independent extraction by observers. Results 21 trials were included, focusing on atenolol, bisoprolol, bucindolol, carvedilol, metoprolol, and nebivolol. As expected, in the overall analysis, β blockers provided credible mortality benefits in comparison with placebo or standard treatment after a median of 12 months (odds ratio 0.69, 0.56 to 0.80). However, no obvious differences were found when comparing the different β blockers head to head for the risk of death, sudden cardiac death, death due to pump failure, or drug discontinuation. Accordingly, improvements in left ventricular ejection fraction were also similar irrespective of the individual study drug. Conclusion The benefits of β blockers in patients with heart failure with reduced ejection fraction seem to be mainly due to a class effect, as no statistical evidence from current trials supports the superiority of any single agent over the others.

New Oral Anticoagulants and the Risk of Intracranial Hemorrhage: Traditional and Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials of New Oral Anticoagulants in Atrial Fibrillation

IMPORTANCE Randomized studies have shown a decreased risk of intracranial hemorrhage (ICH) with use of novel oral anticoagulants (NOACs). However, it is unclear whether the magnitude of benefit is similar for all NOACs currently available. OBJECTIVE To perform a systematic review and meta-analysis to quantitatively assess the rates of ICH within the framework of both conventional and Bayesian statistics. DATA SOURCES The MEDLINE, CENTRAL, CINAHL, and EBSCO databases, supplemented with conference abstracts, were searched up to December 1, 2012, with no language restriction. STUDY SELECTION Randomized trials comparing NOACs vs a comparator and reporting on ICH events. DATA EXTRACTION AND SYNTHESIS The NOACs were pooled to perform a comparison with all comparators and among themselves in both traditional frequentist and Bayesian random-effects models using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled odds ratios and associated 95% confidence intervals as well as numbers needed to treat and 95% credible intervals for the Bayesian analysis. MAIN OUTCOMES AND MEASURES Intracranial hemorrhage events associated with NOACs in comparison with comparators, expressed as odds ratios. RESULTS Six studies (1 administering dabigatran etexilate mesylate, 2 administering rivaroxaban, and 3 administering apixaban) enrolling a total of 57,491 patients were included for analysis. The NOACs significantly reduced the risk of ICH against all comparators (odds ratio = 0.49; 95% CI, 0.36-0.65). Each of the 3 drugs reduced the risk of ICH, with Bayesian indirect comparison analysis not revealing a significant credible difference between the specific medications. CONCLUSIONS AND RELEVANCE Novel oral anticoagulants are uniformly associated with an overall reduced risk of ICH when used for stroke prevention in atrial fibrillation. Any of the currently available NOACs can be considered first line for patients at high risk for ICH.

New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials.

To evaluate the efficacy and safety of new oral anticoagulants (NOACs) in elderly adults.

Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials

BACKGROUND Some glucose-lowering drugs or strategies adversely affect cardiovascular outcomes. We aimed to assess the extent to which glucose lowering by various drugs or strategies increases the risk of heart failure in patients with or at risk for type 2 diabetes, and to establish whether risk is associated with achieved differences in glycaemia or weight control. METHODS We searched Ovid Medline, the Cochrane Library, and meeting abstracts up to Feb 20, 2015, for large randomised controlled trials of glucose-lowering drugs or strategies that assessed cardiovascular outcomes. The primary endpoint was incidence of heart failure. We derived pooled risk ratios (RRs) with random-effects models. FINDINGS We included data from 14 trials, with mean duration 4·3 (2·3) years, comprising 95 502 patients, of whom 3907 (4%) patients developed a heart failure event. Glucose-lowering drugs or strategies were associated with a 0·50% (SD 0·33) reduction in HbA1c and a 1·7 kg (2·8) weight gain. Overall, glucose-lowering drugs or strategies increased the risk of heart failure compared with standard care (RR 1·14, 95% CI 1·01-1·30; p=0·041). The magnitude of this effect varied dependent on the method of glucose lowering (p for interaction=0·00021). Across drug classes, risk was highest with peroxisome proliferator-activated receptor agonists (RR 1·42, 95% CI 1·15-1·76; six trials), intermediate with dipeptidyl peptidase-4 inhibitors (1·25, 1·08-1·45; two trials), and neutral with insulin glargine (0·90, 0·77-1·05; one trial). Target-based intensive glycaemic control strategies (RR 1·00, 95% CI 0·88-1·13; four trials) and intensive weight loss (0·80, 95% CI 0·62-1·04; one trial) were also not associated with development of heart failure. Meta-regression analysis showed that for every 1·0 kg of weight gain associated with glucose-lowering drugs or strategies, there was a 7·1% (95% CI 1·0-13·6) relative increase in the risk of heart failure compared with standard care (p=0·022). INTERPRETATION Compared with standard care, glycaemic lowering by various drugs or strategies might increase the risk of heart failure, with the magnitude of risk dependent on the method of glucose lowering and, potentially, weight gain. FUNDING None.

Novel Oral Anticoagulants in Patients With Renal Insufficiency: A Meta-analysis of Randomized Trials

BACKGROUND Recent reports suggest altered antithrombotic efficacy and higher risk of bleeding with new oral anticoagulants (NOACs) in patients with renal insufficiency. A meta-analysis was performed to evaluate the efficacy and safety with recommended doses of NOAC compared with conventional treatment in patients with renal insufficiency. METHODS PubMed, Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched from January 1, 2001 through March 23, 2014. Randomized controlled trials that compared NOACs (rivaroxaban, apixaban, and dabigatran) with comparators (vitamin K antagonist/warfarin, low molecular weight heparin, aspirin, placebo) were selected. We defined moderate renal insufficiency as creatinine clearance (estimated glomerular filtration rate [eGFR]) of 30-49 mL/min, and mild renal insufficiency as eGFR 50-79 mL/min. RESULTS There were 40,693 patients with renal insufficiency in 10 trials. Compared with other anticoagulants in patients with mild renal insufficiency there was significantly less major or clinically relevant nonmajor bleeding (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.72-0.90) and stroke or systemic embolism (OR, 0.70; 95% CI, 0.54-0.92) with NOACs. Using random effects meta-analysis, there was significantly less stroke or systemic embolism (OR, 0.72; 95% CI, 0.57-0.92) and a trend toward less major or clinically relevant nonmajor bleeding (OR, 0.82; 95% CI, 0.59-1.14) with the NOACs among patients with moderate renal insufficiency, and this became statistically significant when evaluated using a fixed effects model. NOACs showed efficiency comparable with conventional anticoagulants for prevention of venous thromboembolism or related mortality. CONCLUSIONS In patients with renal insufficiency, recommended doses of novel anticoagulants are noninferior and relatively safe compared with conventional anticoagulants.

New Oral Anticoagulants Are Not Superior to Warfarin in Secondary Prevention of Stroke or Transient Ischemic Attacks, but Lower the Risk of Intracranial Bleeding: Insights from a Meta-Analysis and Indirect Treatment Comparisons

Purpose Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA). Methods Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively. Results In patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban. Conclusion NOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding.

Health Resource Variability in the Achievement of Optimal Performance and Clinical Outcome in Ischemic Heart Disease

A disparity between evidence and practice in the management of ischemic heart disease is frequently observed. Guideline adherence and clinical outcomes are influenced by system, provider, and patient factors. Recently, performance improvement measures for cardiovascular disease have gained a lot of popularity worldwide. These measures may facilitate the uptake of evidence-based recommendations and improve patient outcomes. While apparently valid as quality metrics, their impacts on clinical outcomes remain limited and are areas of further research. Several methods for optimizing performance have been instituted and essentially involve three different approaches—improvement in the reporting of data on guideline adherence, providing infrastructure and tools, and providing incentives to improve guideline adherence. Public reporting of quality metrics and “pay-for-performance” are some novel performance improvement tools. The impact of these approaches on patient outcomes will be pivotal in improving cardiovascular outcomes in the future.