Bleeding Outcomes After Left Atrial Appendage Closure Compared With Long-Term Warfarin: A Pooled,Patient-Level Analysis of the WATCHMAN Randomized Trial Experience

ObjectivesThe purpose of this study was to compare the relative risk of major bleeding with left atrial appendage (LAA) closure compared with long-term warfarin therapy.BackgroundLAA closure is an alternative approach to chronic oral anticoagulation for the prevention of thromboembolism in patients with atrial fibrillation (AF).MethodsWe conducted a pooled, patient-level analysis of the 2 randomized clinical trials that compared WATCHMAN (Boston Scientific, Natick, Massachusetts) LAA closure with long-term warfarin therapy in AF.ResultsA total of 1,114 patients were included, with a median follow-up of 3.1 years. The overall rate of major bleeding from randomization to the end of follow-up was similar between treatment groups (3.5 events vs. 3.6 events per 100 patient-years; rate ratio [RR]: 0.96; 95% confidence interval [CI]: 0.66 to 1.40; p = 0.84). LAA closure significantly reduced bleeding >7 days post-randomization (1.8 events vs. 3.6 events per 100 patient-years; RR: 0.49; 95% CI: 0.32 to 0.75; p = 0.001), with the difference emerging 6 months after randomization (1.0 events vs. 3.5 events per 100 patient-years; RR: 0.28; 95% CI: 0.16 to 0.49; p < 0.001), when patients assigned to LAA closure were able to discontinue adjunctive oral anticoagulation and antiplatelet therapy. The reduction in bleeding with LAA closure was directionally consistent across all patient subgroups.ConclusionsThere was no difference in the overall rate of major bleeding in patients assigned to LAA closure compared with extended warfarin therapy over 3 years of follow-up. However, LAA closure significantly reduced bleeding beyond the procedural period, particularly once adjunctive pharmacotherapy was discontinued. The favorable effect of LAA closure on long-term bleeding should be considered when selecting a stroke prevention strategy for patients with nonvalvular AF. (WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy [PREVAIL]; NCT01182441)     

Effectiveness and Safety of Anticoagulants in Adults with Non-valvular Atrial Fibrillation and Concomitant Coronary/Peripheral Artery Disease

Background

Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease.

Should aspirin be continued in patients started on warfarin?

BACKGROUND AND OBJECTIVE: Clinicians frequently face the decision of whether to continue aspirin when starting patients on warfarin. We performed a meta-analysis to characterize the tradeoffs involved in this common clinical dilemma. DATA SOURCES: Multiple computerized databases (1966 to 2003), reference lists of relevant articles, conference proceedings, and queries of primary authors. STUDY SELECTION: Randomized trials comparing warfarin plus aspirin versus warfarin alone. Studies with target international normalized ratios (INRs) <2 were excluded. DATA EXTRACTION: Two reviewers independently extracted baseline data and major outcomes: rates of thromboembolism, hemorrhage, and all-cause mortality. DATA SYNTHESIS: Nine studies met the inclusion criteria. Of the five that enrolled patients with mechanical heart valves, four used the same target INR in both groups, while one used a reduced target INR for the warfarin plus aspirin group. Pooling the results of the first four studies demonstrated that combination of warfarin plus aspirin significantly decreased thromboembolic events (relative risk [RR], 0.33; 95% confidence interval [CI], 0.19 to 0.58), increased major bleeding (RR, 1.58; 95% CI, 1.02 to 2.44), and decreased all-cause mortality (RR, 0.43; 95% CI, 0.23 to 0.81) compared to warfarin alone. The one valve trial using a reduced INR in the warfarin plus aspirin group reported no difference in thromboembolic outcomes but found decreased major bleeding and a significant mortality benefit with combination therapy. Of the remaining trials, three evaluated a warfarin indication not routinely used in the United States (post-myocardial infarction), and the only trial that considered atrial fibrillation was terminated early due to inadequate enrollment. CONCLUSIONS: For mechanical heart valve patients, the benefits of continuing aspirin when starting warfarin therapy are clear. For other routine warfarin indications, there are not adequate data to guide this common clinical decision.     

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.     

Safety and Efficacy of Ultra Short-duration Dual Antiplatelet Therapy After Percutaneous Coronary Interventions: A Meta-analysis of Randomized Controlled Trials

Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention (PCI) to reduce stent thrombosis, but DAPT increases bleeding risks. The optimal duration of DAPT that provides the maximum protective ischemic effect along with the minimum bleeding risk is unclear. This is the first meta-analysis comparing outcomes for 1-month versus longer DAPT strategies following PCI.We searched PubMed, Cochrane, and ClinicalTrials.gov databases (from inception to October 2021) for randomized controlled trials that compared 1-month duration vs > 1-month duration of DAPT following PCI. We used a random-effects model to calculate risk ratio (RR) with 95% confidence interval (CI). The co-primary outcomes for study selection were all-cause mortality, major bleeding, and stent thrombosis. Secondary outcomes included myocardial infarction (MI), cardiovascular mortality, ischemic stroke and target vessel revascularization. A total of five randomized controlled trials were included [n = 29,355; 1-month DAPT(n = 14,662) vs > 1-month DAPT (n = 14,693)]. There was no statistically significant difference between the two groups in terms of all-cause mortality (RR 0.89; 95% CI 0.78-1.03; P = 0.12) and stent thrombosis (RR 1.07; 95% CI 0.80-1.43; P = 0.65). Similarly, there were no significant differences in MI, cardiovascular mortality, ischemic stroke, and target vessel revascularization. The rate of major bleeding was significantly lower in the group treated with DAPT for 1-month (RR 0.74; 95% CI 0.56-0.99, P = 0.04).There is no difference in all-cause mortality, cardiovascular mortality, MI, stent thrombosis, ischemic stroke, and target vessel revascularization with 1-month of DAPT following PCI with contemporary drug eluting stents compared to longer DAPT duration.     

Stroke Event Rates and the Optimal Antithrombotic Choice of Patients With Paroxysmal Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The risks of stroke or systemic embolism and major bleeding are considered similar between paroxysmal and sustained atrial fibrillation (AF), and warfarin has demonstrated superior efficacy to aspirin, irrespective of the AF type. However, with the advent of novel oral anticoagulants (NOACs) and antiplatelet agents, the optimal antithrombotic prophylaxis for paroxysmal AF remains unclear.We searched Medline, Embase, CENTRAL, and China Biology Medicine up to October week 1, 2015. Randomized controlled trials of AF patients assigned to NOACs, warfarin, or antiplatelets, with reports of outcomes stratified by the AF type, were included. A fixed-effects model was used if no statistically significant heterogeneity was indicated; otherwise, a random-effects model was used.Six studies of 69,990 nonvalvular AF patients with ≥1 risk factor for stroke were included. Postantithrombotic treatment, paroxysmal AF patients showed lower risks of stroke (risk ratio [RR], 0.72; 95% confidence interval [CI], 0.59–0.87), stroke or systemic embolism (RR, 0.74; 95% CI, 0.63–0.86), and all-cause mortality (RR, 0.75; 95% CI, 0.67–0.83), while the major bleeding risk was comparable (RR, 0.96; 95% CI, 0.85–1.08). We were unable to detect the superiority of anticoagulation over antiplatelets for paroxysmal AF (RR, 0.72; 95% CI, 0.43–1.23), while it was more effective than antiplatelets for sustained AF (RR, 0.42; 95% CI, 0.33–0.54). NOACs showed superior efficacy over warfarin and trended to show reduced major bleeding irrespective of the AF type.The AF type is a predictor for thromboembolism, and might be helpful in stroke risk stratification model in combination with other risk factors. With the appearance of novel anticoagulant and antiplatelet agents, the best antithrombotic choice for paroxysmal AF needs further exploration.     

Lower dose direct oral anticoagulants and improved survival: A combined analysis in patients with established atherosclerosis

BackgroundAntithrombotic/anticoagulation effects of direct oral anticoagulants (DOACs) are dose-dependent. However, recent observations suggest that administering lower dose DOACs may better protect against all-cause mortality. We investigated whether, in patients with established atherosclerosis, DOAC dose selection would affect the risk of all-cause mortality.MethodsWe performed a structured literature research for controlled trials allowing random assignment to a lower dose DOAC, a higher dose DOAC, or control therapy in patients with established atherosclerosis. Pooled risk ratios (RRs) of all-cause mortality in lower and higher dose DOACs versus control therapy were estimated using a random-effect model.ResultsAtherosclerosis manifested as acute coronary syndrome (n=17,220), stable coronary (CAD) and/or peripheral artery disease (PAD) (n=27,395) or CAD associated with atrial fibrillation (n=4,510). Antithrombotic doses of rivaroxaban (2.5 mg or 5.0 mg BID) or dabigatran (50 mg, 75 mg, 110 mg, or 150 mg, BID) were tested in three trials versus single or dual antiplatelet control therapy, whereas anticoagulation doses of edoxaban (30 mg or 60 OD) were tested versus warfarin in one trial. Compared to control, patients receiving lower dose (RR 0.80, 95% CI 0.73-0.89, p<0.0001, I²=0%), but not those receiving higher dose DOACs (RR 0.95, 95% CI 0.87-1.05, p=0.3074, I²=0%), had a significant reduction of all-cause mortality. Benefit from lower dose DOACs remained after sensitivity analysis or direct comparison with higher dose DOACs (RR 0.84, 95% CI 0.76-0.93, p=0.0009, I²=0%).ConclusionsWithin antithrombotic/anticoagulation regimens of DOAC administration, selection of lower dose appears to protect from all-cause mortality in patients with established atherosclerosis.     

Oral Anticoagulants and Antiplatelet Agents in Patients With Atrial Fibrillation and Concomitant Critical Limb Ischemia: A Nationwide Cohort Study

BackgroundEvidence of clinical outcomes for oral anticoagulants and antiplatelet treatment (APT) in patients with atrial fibrillation (AF) and critical limb ischemia (CLI) is very limited.MethodsIn this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, 1223 patients with AF and CLI taking direct-acting oral coagulants (DOACs), warfarin, or APT were identified from June 1, 2012, to December 31, 2017. We used propensity score stabilized weighting (PSSW) to balance covariates across study groups.ResultsAfter PSSW, DOAC (n = 446) was associated with lower risks of ischemic stroke/systemic embolism (IS/SE), all major adverse limb events, and all major bleeding events compared with warfarin (n = 237). DOAC was associated with lower risks of IS/SE, acute myocardial infarction (AMI), and all major adverse limb events and a comparable risk of major bleeding events compared with APT (n = 540). DOAC has a lower risk of composite net-clinical-benefit outcome (IS/SE, AMI, all major adverse limb events, plus all major bleeding events) compared with warfarin (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.35-0.65; P < 0.0001) or APT (HR: 0.44; 95% CI: 0.34-0.56; P < 0.0001). The composite net-clinical-benefit outcome was comparable for warfarin vs APT. The reduced risk of net-clinical-benefit outcome for DOAC vs warfarin or APT persisted in high subgroups including age > 75 years, presence of diabetes mellitus, or chronic kidney disease.ConclusionsDOAC was associated with a significantly lower risk of composite net-clinical-benefit outcome than either warfarin or APT in patients with AF and concomitant CLI. Further prospective study is necessary to validate the findings in the future.     

Rescue angioplasty or repeat fibrinolysis after failed fibrinolytic therapy for ST-segment myocardial infarction: a meta-analysis of randomized trials.

OBJECTIVES: We sought to best estimate the benefits and risks associated with rescue percutaneous coronary intervention (PCI) and repeat fibrinolytic therapy as compared with conservative management in patients with failed fibrinolytic therapy for ST-segment myocardial infarction (STEMI). BACKGROUND: Fibrinolytic therapy is the most common treatment for STEMI; however, the best therapy in patients who fail to achieve reperfusion after fibrinolytic therapy remains uncertain. METHODS: We performed a meta-analysis of randomized trials using a fixed-effects model. We included 8 trials enrolling 1,177 patients with follow-up duration ranging from hospital discharge to 6 months. RESULTS: Rescue PCI was associated with no significant reduction in all-cause mortality (relative risk [RR] 0.69; 95% confidence interval [CI] 0.46 to 1.05), but was associated with significant risk reductions in heart failure (RR 0.73; 95% CI 0.54 to 1.00) and reinfarction (RR 0.58; 95% CI 0.35 to 0.97) when compared with conservative treatment. Rescue PCI was associated with an increased risk of stroke (RR 4.98; 95% CI 1.10 to 22.5) and minor bleeding (RR 4.58; 95% CI 2.46 to 8.55). Repeat fibrinolytic therapy was not associated with significant improvements in all-cause mortality (RR 0.68; 95% CI 0.41 to 1.14) or reinfarction (RR 1.79; 95% CI 0.92 to 3.48), but was associated with an increased risk for minor bleeding (RR 1.84; 95% CI 1.06 to 3.18). CONCLUSIONS: Rescue PCI is associated with improved clinical outcomes for STEMI patients after failed fibrinolytic therapy, but these benefits must be interpreted in the context of potential risks. On the other hand, repeat fibrinolytic therapy is not associated with significant clinical improvement and may be associated with increased harm.     

The risk of gastrointestinal hemorrhage with non-vitamin K antagonist oral anticoagulants: A network meta-analysis

Background:Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for stroke prevention in atrial fibrillation (AF) and the treatment and prevention of venous thromboembolism. There is an issue with safety, especially in clinically relevant bleeding. We performed a network meta-analysis to evaluate the risk of major gastrointestinal (GI) bleeding associated with NOACs.Methods:Interventions were warfarin, enoxaparin, apixaban, dabigatran, edoxaban, and rivaroxaban. The primary outcome was the incidence of major GI bleeding. A subgroup analysis was performed according to the following indications: AF, deep venous thrombosis/pulmonary embolism, and postsurgical prophylaxis.Results:A total of 29 randomized controlled trials (RCTs) and 4 large observation population studies were included. Compared with warfarin, apixaban showed a decreased the risk of major GI bleeding (relative risk [RR] 0.54, 95% confidence interval [CI] 0.25–0.76), and rivaroxaban tended to increase this risk (RR 1.40, 95% CI 1.06–1.85). Dabigatran (RR 1.25, 95% CI 0.98–1.60), edoxaban (RR 1.07, 95% CI 0.69–1.65), and enoxaparin (RR 1.24, 95% CI 0.63–2.43) did not significantly increase the risk of GI bleeding than did warfarin. In the subgroup analysis, according to indications, apixaban showed a decreased risk of major GI bleeding (RR 0.50, 95% CI 0.34–0.74) than did warfarin in AF studies. Dabigatran (RR 2.36, 95% CI 1.55–3.60, and rivaroxaban (RR 1.75, 95% CI 1.10–6.41) increased the risk of major GI bleeding than did apixaban. An analysis of studies on venous thromboembolism or pulmonary embolism showed that no individual NOAC or enoxaparin was associated with an increased risk of major GI bleeding compared to warfarin.Conclusion:Individual NOACs had varying profiles of GI bleeding risk. Results of analyses including only RCTs and those including both RCTs and population studies showed similar trends, but also showed several differences.     

P2Y12 Inhibitors versus Aspirin Monotherapy for Long-term Secondary Prevention of Atherosclerotic Cardiovascular Disease Events: A Systematic Review and Meta-analysis

Patients with established atherosclerotic cardiovascular disease (ASCVD) need long-term antiplatelet therapy to decrease the risk of future ASCVD events. We searched PubMed, Cochrane Library, and ClinicalTrials.gov (inception through September 2021) for randomized controlled trials (RCTs) evaluating P2Y₁₂ inhibitors vs aspirin for secondary prevention of ASCVD events. Seven RCTs including a total of 56,982 patients were included in this analysis. The median follow-up duration was 22.8 (IQR 12) months. When P2Y₁₂ inhibitors were compared with aspirin as long-term antiplatelet therapy for secondary prevention of ASCVD events, there was a significant decrease in the risk of myocardial infarction [RR: 0.83; 95% CI: 0.72-0.94], and stroke [RR: 0.90; 95% CI: 0.83-0.99]. However, there was no significant difference in all-cause mortality [RR: 1.02; 95% CI: 0.92-1.12], or cardiovascular mortality [RR: 0.95; 95% CI: 0.83-1.08] between P2Y₁₂ inhibitors and aspirin users. Additionally, there was no significant difference in major bleeding events [RR: 0.88; 95% CI: 0.74-1.04], or all bleeding events [RR: 1.09; 95% CI: 0.90-1.33] between P2Y₁₂ inhibitors and aspirin groups. Use of P2Y₁₂ inhibitor monotherapy is associated with lower rates of myocardial infarction and stroke in ASCVD patients without any significant difference in mortality, or bleeding compared to aspirin monotherapy.     

Half-Dose Direct Oral Anticoagulation Versus Standard Antithrombotic Therapy After Left Atrial Appendage Occlusion

ObjectivesThis study evaluated the long-term efficacy of a standard antithrombotic strategy versus half-dose direct oral anticoagulation (DOAC) after Watchman implantation.BackgroundNo consensus currently exists on the selection of the most effective antithrombotic strategy to prevent device-related thrombosis (DRT) in patients undergoing endocardial left atrial appendage closure.MethodsAfter successful left atrial appendage closure, consecutive patients were prescribed a standard antithrombotic strategy (SAT) or long-term half-dose DOAC (hdDOAC). The primary composite endpoint was DRT and thromboembolic (TE) and bleeding events.ResultsOverall, 555 patients (mean age 75 ± 8 years, 63% male; median CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category] score 4 [interquartile range (IQR): 3-6]; median HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] score 3 [IQR: 2-4]) were included. Patients were categorized into 2 groups (SAT: n = 357 vs hdDOAC: n = 198). Baseline clinical characteristics were similar between groups. The median follow-up duration was 13 months (IQR: 12-15 months). DRT occurred in 12 (2.1%) patients, all in the SAT group (3.4% vs 0.0%; log-rank P = 0.009). The risk of nonprocedural major bleeding was significantly more favorable in the hdDOAC group (0.5% vs. 3.9%; log-rank P = 0.018). The rate of the primary composite endpoint of DRT and TE and major bleeding events was 9.5% in SAT patients and 1.0% in hdDOAC patients (HR: 9.8; 95% CI: 2.3-40.7; P = 0.002).ConclusionsAfter successful Watchman implantation, long-term half-dose DOAC significantly reduced the risk of the composite endpoint of DRT and TE and major bleeding events compared with a standard, antiplatelet-based, antithrombotic therapy.     

Efficacy and Safety Outcomes of Direct Oral Anticoagulants and Amiodarone in Patients with Atrial Fibrillation

Background

Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug–drug interaction by the concomitant use of DOACs and amiodarone.

Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials

OBJECTIVES: The aim of this study was to determine whether multidisciplinary strategies improve outcomes for heart failure (HF) patients. BACKGROUND: Because the prognosis of HF remains poor despite pharmacotherapy, there is increasing interest in alternative models of care delivery for these patients. METHODS: Randomized trials of multidisciplinary management programs in HF were identified by searching electronic databases and bibliographies and via contact with experts. RESULTS: Twenty-nine trials (5,039 patients) were identified but were not pooled, because of considerable heterogeneity. A priori, we divided the interventions into homogeneous groups that were suitable for pooling. Strategies that incorporated follow-up by a specialized multidisciplinary team (either in a clinic or a non-clinic setting) reduced mortality (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.59 to 0.96), HF hospitalizations (RR 0.74, 95% CI 0.63 to 0.87), and all-cause hospitalizations (RR 0.81, 95% CI 0.71 to 0.92). Programs that focused on enhancing patient self-care activities reduced HF hospitalizations (RR 0.66, 95% CI 0.52 to 0.83) and all-cause hospitalizations (RR 0.73, 95% CI 0.57 to 0.93) but had no effect on mortality (RR 1.14, 95% CI 0.67 to 1.94). Strategies that employed telephone contact and advised patients to attend their primary care physician in the event of deterioration reduced HF hospitalizations (RR 0.75, 95% CI 0.57 to 0.99) but not mortality (RR 0.91, 95% CI 0.67 to 1.29) or all-cause hospitalizations (RR 0.98, 95% CI 0.80 to 1.20). In 15 of 18 trials that evaluated cost, multidisciplinary strategies were cost-saving. CONCLUSIONS: Multidisciplinary strategies for the management of patients with HF reduce HF hospitalizations. Those programs that involve specialized follow-up by a multidisciplinary team also reduce mortality and all-cause hospitalizations.     

Aspirin for Primary Prevention of Cardiovascular Events

BackgroundThe efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.ObjectivesThe purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.MethodsRandomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.ResultsA total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.ConclusionsAspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.     

Non-Vitamin K Antagonists Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review and Meta-Analysis

BackgroundPatients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral anticoagulants (NOACs), as a class, relative to warfarin in this population is not well-known. We aimed to compare the efficacy and safety of NOACs relative to warfarin in patients with bioprosthetic valves or valve repair.MethodsWe systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials comparing NOACs to warfarin in patients with atrial fibrillation and bioprosthetic valves or valve repair. We pooled outcomes for stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, and major bleeding.ResultsWe included 4 trials with 1379 patients, of whom 723 (52.4%) received a NOAC. Mean follow-up ranged from 90 days to 2.8 years. In the pooled analysis, stroke or systemic embolism was significantly lower in patients treated with NOACs (1.9%) compared with warfarin (3.7%) (odds ratio [OR] 0.43; 95% confidence interval [CI] 0.22-0.85; P = .02). Ischemic stroke (OR 0.72; 95% CI 0.18-2.93), hemorrhagic stroke (OR 0.18; 95% CI 0.03-1.05), cardiovascular death (OR 0.78; 95% CI 0.38-1.62), and all-cause mortality (OR 0.94; 95% CI 0.55-1.62) were not significantly different among groups. Major bleeding was significantly lower in patients treated with NOAC (2.8%) compared with warfarin (4.7%) (OR 0.49; 95% CI 0.28-0.88; P = .02).ConclusionsIn patients with atrial fibrillation and bioprosthetic valves or valve repair, NOACs are associated with a reduced incidence of thromboembolic events and major bleeding as compared with warfarin. Thus, NOACs may be considered a preferred option for this patient population.     

Thromboembolism,Bleeding, and Mortality Incidence of Direct Oral Anticoagulants Versus Warfarin Postbariatric Surgery

BackgroundThere is no randomized controlled trial comparing direct oral anticoagulants (DOACs) and warfarin following bariatric surgery to date. The mortality, thromboembolism, and bleeding risk of DOACs in comparison with warfarin following bariatric surgery remains unclear. We aimed to provide a clinical comparison between DOACs and warfarin for these 3 prespecified outcomes.MethodsA systematic literature search was performed on November 10, 2019, using PubMed, Embase, clinicaltrial.gov, and Cochrane databases. Studies with adult patients who were on either warfarin or DOACs following bariatric surgery and reported the incidence of thromboembolism, bleeding, or mortality were included. Pooled incidence for these prespecified outcomes and its 95% confidence interval (CI) were calculated for each drug separately using the random-effects model, along with a nonadjusted P value comparing the 2 subgroups.ResultsA total of 11 studies (805 patients) were included. Comparing DOACs to warfarin, the following pooled incidences were observed for mortality (DOACs: 3.0%; 95% CI 0.4%-18.6% versus warfarin: 1.5%; 95% CI 0.8%-2.9%; P value comparing the 2 subgroups = .38), thromboembolism (DOACs: 4.9%; 95% CI 1%-21.1% versus warfarin: 1.5%; 95% CI 0.8%-2.9%; P value = .18), and bleeding (DOACs: 3.9%; 95% CI 0.7%-18.2% versus warfarin: 11.3%; 95% CI 5.7%-21.4%; P value = .23).ConclusionThe results of our meta-analysis remain hypothesis-generating, providing rationale for future randomized controlled trial design or well-designed comparative observational studies. Currently, it does not support the change in the current recommendation from warfarin to DOACs following bariatric surgery.     

Body mass index and colorectal cancer prognosis: a systematic review and meta-analysis

Colorectal cancer is one of the most common cancers worldwide. However, it is unclear what influence body mass index (BMI) has on colorectal cancer prognosis. We conducted a systematic review and meta-analysis of observational studies to examine the association of BMI with colorectal cancer outcomes. We searched MEDLINE and EMBASE databases from inception to February 2015 and references of identified articles. We selected observational studies that reported all-cause mortality, colorectal cancer-specific mortality, recurrence and disease-free survival according to BMI category. Random-effects meta-analyses were conducted to combine estimates. We included 18 observational studies. Obese patients had an increased risk of all-cause mortality [relative risk (RR) 1.14; 95 % confidence interval (CI) 1.07–1.21], cancer-specific mortality (RR 1.14; 95 % CI 1.05–1.24), recurrence (RR 1.07; 95 % CI 1.02–1.13) and worse disease-free survival (RR 1.07; 95 % CI 1.01–1.13). Underweight patients also had an increased risk of all-cause mortality (RR 1.43; 95 % CI 1.26–1.62), cancer-specific mortality (RR 1.50; 95 % CI 1.20–1.87), recurrence (RR 1.13; 95 % CI 1.05–1.21) and worse disease-free survival (RR 1.27; 95 % CI 1.13–1.43). Overweight patients had no increased risk for any of the outcomes studied. Both obese and underweight patients with colorectal cancer have an increased risk of all-cause mortality, cancer-specific mortality, disease recurrence and worse disease-free survival compared to normal weight patients.     

Comprehensive Meta-Analysis on Drug-Eluting Stents versus Bare-Metal Stents during Extended Follow-up

Background

Several observational reports have documented both increased and decreased cardiac mortality or Q-wave myocardial infarction with drug-eluting stents compared with bare-metal stents.

Methods

We sought to evaluate the safety and efficacy of drug-eluting stents compared with bare-metal stents early after intervention (<1 year) and late (>1 year) among a broad population of patients, using a meta-analysis of randomized clinical trials.

Results

We identified 28 trials with a total of 10,727 patients and a mean follow-up of 29.6 months. For early outcomes (<1 year), all-cause mortality for drug-eluting stents versus bare-metal stents was 2.1% versus 2.4% (risk ratio [RR] 0.91, [95% confidence interval (CI), 0.70-1.18]; P = .47), non-Q-wave myocardial infarction was 3.3% versus 4.4% (RR 0.78 [95% CI, 0.61-1.00]; P = .055), target lesion revascularization was 5.8% versus 18.4% (RR 0.28 [95% CI, 0.21-0.38]; P <.001), and stent thrombosis was 1.1% versus 1.3% (RR 0.87 [95% CI, 0.60-1.26]; P = .47). For late outcomes (>1 year), all-cause mortality for drug-eluting stents versus bare-metal stents was 5.9% versus 5.7% (RR 1.03 [95% CI, 0.83-1.28]; P = .79), target lesion revascularization was 4.0% versus 3.3% (RR 1.22 [95% CI, 0.92-1.60]; P = .16), non-Q-wave myocardial infarction was 1.6% versus 1.2% (RR 1.36 [95% CI, 0.74-2.53]; P = .32) and stent thrombosis was 0.7% versus 0.1% (RR 4.57 [95% CI, 1.54-13.57]; P = .006).

Conclusions

There was no excess mortality with drug-eluting stents. Within 1 year, drug-eluting stents appear to be safe and efficacious with possibly decreased non-Q-wave myocardial infarction compared with bare-metal stents. After 1 year, drug-eluting stents still have similar mortality, despite increased stent thrombosis. The reduction in target lesion revascularization with drug-eluting stents mainly happens within 1 year, but is sustained thereafter.     

Routine Invasive Strategy in Elderly Patients with Non-ST Elevation Acute Coronary Syndrome: An Updated Systematic Review and Meta-analysis of Randomized Trials

Invasive treatment with coronary angiography is preferred approach for patients with non-ST elevation acute coronary syndrome (NSTE-ACS) compared to medical therapy alone. The results from the randomized clinical trials (RCT) that compared the invasive treatment strategy vs. conservative approach in the elderly (≥75 years) with NSTE-ACS has been inconsistent. To compare invasive and conservative strategies in the elderly (>75 years) with NSTE-ACS. We searched PubMed, Cochrane CENTRAL Register and ClinicalTrials.gov (inception through July 10, 2021) for RCTs comparing invasive and conservative strategies in the elderly with NSTE-ACS. We used random-effects model to calculate risk ratio (RR) with 95% confidence interval(CI). A total of 6 RCT including 2,323 patients were included in the meta-analysis. The median follow-up duration was 13.5 months. When invasive approach was compared to conservative strategy, it showed no difference in all-cause mortality in patients aged ≥75 years with NSTE-ACS (RR of 0.85; 95% CI 0.70–1.04; P = 0.12; I2 = 0%). There was significant reduction in MI (RR 0.59; 95% CI 0.49 0.71; P < 0.001; I2 = 0%) and unplanned revascularization (RR 0.30, 95% CI 0.17-0.53, P <0.001, I2 = 0%). Invasive strategy was associated with higher risk of major bleeding when compared to conservative treatment (RR 2.12, 95% CI 1.21-3.74, P = 0.009, I2 = 0%). Comparison of both strategies showed no significant difference in stroke (RR 0.75; 95% CI 0.38-1.46, P = 0.40; I2 = 0%). This updated meta-analysis suggests that in elderly patients (>75 years) with NSTE-ACS, a routine invasive strategy is associated with a reduction in MI and revascularization, while increasing the risk of major bleeding, but without difference in all-cause mortality and stroke.