Ramez Nairooz

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.

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.

Meta-Analysis of Risk of Stroke or Transient Ischemic Attack With Dabigatran for Atrial Fibrillation Ablation

Dabigatran is a novel oral anticoagulant and may be useful during atrial fibrillation (AF) ablation for prevention of thromboembolic events. However, the benefits and adverse effects of periprocedural dabigatran therapy have not been thoroughly evaluated. A meta-analysis was performed to evaluate the efficacy and safety of dabigatran for anticoagulation in AF ablation. PubMed, The Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched from January 01, 2001 through July 30, 2013. Two reviewers reviewed the studies for inclusion and extracted data from studies comparing dabigatran with warfarin for AF ablation. A total of 5,513 patients undergoing catheter ablation were included in 17 observational studies and 1 randomized trial. Fourteen events of stroke or transient ischemic attacks were reported in the dabigatran group and 4 in the warfarin group (Petos odds ratio 3.94, 95% confidence interval [CI] 1.54 to 10.08, number needed to harm=284 patients). The risk of all thromboembolic complications was also higher in the dabigatran group compared with the warfarin group (Petos odds ratio 2.81, 95% CI 1.23 to 6.45). No major differences were observed for the risk of major bleeding (odds ratio 0.99, 95% CI 0.55 to 1.78), pericardial tamponade, and groin hematoma. A lower risk of minor bleeding was observed with dabigatran (odds ratio 0.60, 95% CI 0.41 to 0.87). In conclusion, periprocedural use of dabigatran for AF ablation was related to a higher risk of thromboembolic complications including stroke and transient ischemic attack.

Endovascular therapy for acute ischaemic stroke: a systematic review and meta-analysis of randomized trials

AIMS Evidence from randomized controlled trials (RCTs) evaluating possible benefits of endovascular therapy (EVT) for acute ischaemic stroke has shown conflicting results. The purpose of this meta-analysis was to systematically examine clinical outcomes in RCTs comparing the use of intravenous (IV) fibrinolysis alone to IV fibrinolysis plus EVT, for the treatment of acute ischaemic stroke. METHODS AND RESULTS We selected English language RCTs, comparing EVT plus IV tissue-type plasminogen activator (tPA) (if eligible) with IV tPA alone in eligible patients for the treatment of acute ischaemic stroke. The primary endpoint was good functional outcome [modified Rankin Scale (mRS) of 0-2]. Other major endpoints of interest were all-cause mortality and symptomatic intracerebral haemorrhage (sICH). The meta-analysis included 8 RCTs that randomized 2423 patients with large-vessel, anterior-circulation stroke. EVT significantly improved the rate of functional independence (90-day mRS of 0-2) when compared with IV fibrinolysis [odds ratio (OR) 1.73, 95% confidence interval (CI) 1.18-2.53, number needed to treat (NNT) = 9.3]. The all-cause mortality was lower with EVT compared with the control group; however, the result did not reach statistical significance (OR 0.89, 95% CI 0.68-1.15). The rate of sICH was not higher with EVT (OR 1.07, 95% CI 0.73-1.56). Analyses from only the recent trials (reported in 2014-15) showed further benefit (OR of mRS 0-2: 2.42, 95% CI 1.91-3.08, NNT = 5) with similar safety results. CONCLUSION In centres with advanced systems of stroke care, EVT significantly improved functional outcomes (without compromising safety) in patients with acute ischaemic stroke due to anterior circulation, large artery occlusion, compared with standard therapy.

Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors in patients with type II diabetes mellitus: A meta-analysis of placebo-controlled randomized trials

BACKGROUND The impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular outcomes in patients with type II diabetes mellitus (DM) is not well established. METHODS We searched electronic databases from inception through July 2016 for randomized, placebo-controlled trials, involving SGLT-2 inhibitors. Fixed-effects summary odds ratios (OR) were constructed using Peto model. RESULTS Eighty-one trials with a total of 37,195 patients were included. The mean follow-up was 89weeks. Compared with placebo, SGLT-2 inhibitors were associated with a lower risk of all-cause mortality (OR 0.72; 95% CI 0.59-0.86; P<0.001), cardiovascular mortality (OR 0.67; 95% CI 0.53-0.84; P=0.001), and heart failure (OR 0.67; 95% CI 0.51-0.87; P=0.003), but a similar risk of myocardial infarction (OR 0.89; 95% CI 0.74-1.09; P=0.29) and stroke/transient ischemic attack (OR 1.09; 95% CI 0.87-1.37; P=0.47). The reduction in all-cause mortality was noticed with empagliflozin (OR 0.66; 95% CI 0.54-0.81; P<0.001), but not with other SGLT-2 inhibitors (ORdapagliflozin 1.37; 95% CI 0.71-2.62; P=0.35; ORcanagliflozin 0.82; 95% CI 0.41-1.68; P=0.59; ORluseogliflozin 4.6; 95% CI 0.07-284.25; P=0.47; and ORipragliflozin 4.73; 95% CI 0.08-283.14; P=0.46) (Pinteraction=0.19). Potential harm was observed with dapagliflozin on cardiovascular mortality (OR 2.15, 95% CI 0.92-5.04, P=0.08). CONCLUSIONS In patients with type II DM, SGLT-2 inhibitors appeared to reduce both all-cause and cardiovascular mortality, primarily due to reduction in the risk of heart failure. The benefit was only seen with empagliflozin. There was suggestion of potential harm with dapagliflozin, thus future trials are needed to ascertain the cardiovascular safety of other agents in this class.

Remote ischemic preconditioning in patients undergoing cardiovascular surgery: Evidence from a meta-analysis of randomized controlled trials

BACKGROUND Remote ischemic preconditioning (RIPC) has been associated with reduced risk of myocardial injury in patients undergoing cardiovascular surgery, but uncertainty about clinical outcomes remains, particularly in the light of 2 recent large randomized clinical trials (RCTs) which were neutral. We performed a meta-analysis to evaluate the efficacy of RIPC on clinically relevant outcomes in patients undergoing cardiovascular surgery. METHODS We searched PubMed, Cochrane CENTRAL, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through November 30, 2015. RCTs that compared the effects of RIPC vs. control in patients undergoing cardiac and/or vascular surgery were selected. We calculated summary random-effect odds ratios (ORs) and 95% confidence intervals (CI). RESULTS The analysis included 5652 patients from 27 RCTs. RIPC reduced the risk of myocardial infarction (MI) (OR 0.72, 95% CI, 0.52 to 1.00; p=0.05; number needed to treat (NNT)=42), acute renal failure (OR 0.73, 95% CI, 0.53 to 1.00; p=0.05; NNT=44) as well as the composite of all cause mortality, MI, stroke or acute renal failure (OR 0.60, 95% CI, 0.39 to 0.90; p=0.01; NNT=25). No significant difference between RIPC and the control groups was observed for the outcome of all-cause mortality (OR 1.10, 95% CI, 0.81 to 1.51). Randomization to RIPC group was also associated with significantly shorter hospital stay (weighted mean difference -0.15days; 95% CI -0.27 to -0.03days). CONCLUSIONS RIPC did not decrease overall mortality, but was associated with less MI and acute renal failure and shorter hospitalizations in patients undergoing cardiac or vascular surgery.

U.S. Trends in Inpatient Utilization of Fractional Flow Reserve and Percutaneous Coronary Intervention.

Fractional flow reserve (FFR) of intermediate coronary stenosis is a highly accurate, reproducible, and cost-effective modality with powerful prognostic value. Results of the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) [(1)][1] and FAME-2 trials [(2)][2] have shown a

Meta-Analysis of Randomized Clinical Trials Comparing Bivalirudin Versus Heparin Plus Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention and in Patients With ST-Segment Elevation Myocardial Infarction

This study sought to investigate the relative safety and efficacy of bivalirudin versus heparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI) and in those with ST-segment elevation myocardial infarction (STEMI). The safety of bivalirudin in PCI, particularly in patients with STEMI, continues to be debated. We searched the on-line databases for randomized controlled trials of bivalirudin versus heparin plus GP IIb/IIIa inhibitors. Data on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes at 30 days were extracted. A total of 19,856 PCI patients included in 7 randomized trials and 5,820 patients with STEMI included in 2 randomized trials were separately analyzed. At 30 days, bivalirudin use in patients undergoing PCI resulted in similar rates of death, myocardial infarction, repeat revascularization, and stent thrombosis. In patients with STEMI, bivalirudin use resulted in decreased cardiac mortality (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.50 to 0.97, p=0.03) compared with heparin plus GP IIb/IIIa inhibitors but an increase in definite stent thrombosis at 30 days (RR 1.88, 95% CI 1.09 to 3.24, p=0.02) driven by an increase in acute stent thrombosis (RR 5.48, 95% CI 2.30 to 13.07, p=0.0001). Bivalirudin use was associated with a decrease in Thrombolysis In Myocardial Infarction (TIMI) major (RR 0.58, 95% CI 0.46 to 0.74, p<0.0001) and TIMI minor (RR 0.55, 95% CI 0.48 to 0.63, p<0.0001) bleeding rates in PCI patients as well as in a subgroup of patients with STEMI. In conclusion, in PCI patients anticoagulation with bivalirudin results in similar ischemic adverse events and a reduction in TIMI major and minor bleeding at 30 days compared with heparin plus GP IIb/IIIa inhibitors. In patients with STEMI, bivalirudin use is associated with a reduction in TIMI major and minor bleeding and fewer deaths from cardiac causes but an increase in acute and 30-day definite stent thrombosis.

Long-term cardiovascular mortality after radiotherapy for breast cancer: a systematic review and meta-analysis

Radiotherapy (RT) is frequently associated with late cardiovascular (CV) complications. The mean cardiac dose from irradiation of a left‐sided breast cancer is much higher than that for a right‐sided breast cancer. However, data is limited on the long‐term risks of RT on CV mortality.

Meta-analysis of risk of stroke and thrombo-embolism with rivaroxaban versus vitamin K antagonists in ablation and cardioversion of atrial fibrillation.

BACKGROUND Anticoagulation in cardioversion and ablation of atrial fibrillation is imperative for reducing thrombo-embolic events. Ample information is available about the use of warfarin and vitamin K antagonists (VKA) but few trials examine safety and efficacy of rivaroxaban in these procedures. We aim to explore the hypothesis that rivaroxaban causes equal thrombo-embolic and bleeding events when used in atrial fibrillation patients undergoing ablation or cardioversion compared to VKA. METHODS We searched the online databases as well as conference abstracts till December 2014 for studies comparing rivaroxaban with VKA in atrial fibrillation patients undergoing catheter ablation or cardioversion. We report events as Odds ratio using random effects model except when event rates were less than 1% we used Peto Odds Ratio. RESULTS A total of 8872 atrial fibrillation patients in 15 studies undergoing either catheter ablation or cardioversion were included in this analysis. There were significantly lower stroke events with rivaroxaban compared with VKA (Peto Odds Ratio (POR) 0.33, 95% confidence interval (CI) [0.11, 0.95]; P=0.04), and significantly less thrombo-embolic events with rivaroxaban compared with VKA (POR 0.46, 95% CI [0.21, 0.97]; P=0.04). Major and minor bleeding were equal with rivaroxaban versus VKA (Odds Ratio (OR) 0.92, 95% CI [0.62, 1.36]; P=0.68) and (OR 0.81,95% CI [0.58, 1.11]; P=0.19) respectively. CONCLUSION The use of rivaroxaban in ablation and cardioversion of atrial fibrillation may be associated with decreased risk of stroke and thromboembolism with equal bleeding risk compared to VKA.