Background The original non–vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit–risk profiles of NOACs versus warfarin in AF patients with native valvular heart disease (VHD). Methods and Results Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta‐analytic summary hazard ratio (HR) and 95% confidence interval (CI) of efficacy and safety of NOACs versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with VHD. Pooling results from included trials showed that NOACs versus warfarin reduced stroke or systemic embolism (HR: 0.70; 95% CI, 0.60–0.82) and intracranial hemorrhage (HR: 0.47; 95% CI, 0.24–0.92) in AF patients with VHD. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95% CI, 0.69–0.91]; HR for intracranial hemorrhage: 0.33 [95% CI, 0.25–0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95% CI, 1.20–2.04]; HR for intracranial hemorrhage: 1.27 [95% CI, 0.77–2.10]). Conclusions Among patients with AF and native VHD, NOACs reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in VHD patients treated with rivaroxaban. NOACs are a reasonable alternative to warfarin in AF patients with VHD.

Background and Purpose—: Elevated blood pressure is common in acute stage of ischemic stroke and the strategy to manage this situation is not well established. We therefore conducted a meta-analysis of randomized controlled trials comparing active blood pressure lowering and control groups in early ischemic stroke. Methods—: Pubmed, EMBASE, and Clinicaltrials.gov from January 1966 to March 2015 were searched to identify relevant studies. We included randomized controlled trials with blood pressure lowering started versus control within 3 days of ischemic stroke onset. The primary outcome was unfavorable outcome at 3 months or at trial end point, defined as dependency or death, and the key secondary outcome was recurrent vascular events. Pooled relative risks and 95% confidence intervals were calculated using random-effects model. Results—: The systematic search identified 13 randomized controlled trials with 12 703 participants comparing early blood pressure lowering and control. Pooling the results with the random-effects model showed that blood pressure lowering in early ischemic stroke did not affect the risk of death or dependency at 3 months or at trial end point (relative risk, 1.04; 95% confidence interval, 0.96–1.13; P =0.35). Also, blood pressure lowering also had neutral effect on recurrent vascular events, as well as on disability or death, all-cause mortality, recurrent stroke, and serious adverse events. Conclusions—: This meta-analysis suggested blood pressure lowering in early ischemic stroke had a neutral effect on the prevention of death or dependency.

Dual-antiplatelet regimens for prevention of recurrent stroke promote antithrombotic effects but may increase the risk for hemorrhage. To qualitatively and quantitatively examine the risk for recurrent stroke and intracranial hemorrhage (ICH) linked to long-term dual- and single-antiplatelet therapy among patients with ischemic stroke and transient ischemic attack. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials through March 2013 without language restrictions. The search identified 7 randomized, controlled trials that involved a total of 39,574 participants and reported recurrent stroke and ICH as outcome measures. All data from eligible studies were independently abstracted by 2 investigators according to a standard protocol. Recurrent stroke risk did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (relative risk [RR], 0.89 [95% CI, 0.78 to 1.01]) or clopidogrel monotherapy (RR, 1.01 [CI, 0.93 to 1.08]). Risk for ICH did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (RR, 0.99 [CI, 0.70 to 1.42]) but was greater among patients receiving dual-antiplatelet therapy than among those receiving clopidogrel monotherapy (RR, 1.46 [CI, 1.17 to 1.82]). Agents used in dual- and single-antiplatelet therapies varied across trials, and the relatively modest number of trials limited subgroup analysis. Compared with monotherapy, dual-antiplatelet therapy lasting more than 1 year after an index ischemic stroke or transient ischemic attack is not associated with a greater reduction in overall recurrent stroke risk. However, long-term dual-antiplatelet therapy is linked to higher risk for ICH than clopidogrel monotherapy in this patient population. Chang Gung Memorial Hospital.

No studies have reported the long-term outcomes of initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m² to predialysis. To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD). Target trial emulation study. Taiwan's National Health Insurance Research Database (NHIRD). By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021. Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers. In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan-Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use. This result may not apply to patients without T2D. This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD. National Health Research Institutes, Taiwan.

Background and Purpose—Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis. Methods—We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model. Results—Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54–0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54–0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit. Conclusions—Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke.

Objective There is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke. Design Retrospective. Setting We conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database. Participants Among 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis. Interventions Patients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010. Primary and secondary outcome measures The primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke. Results Compared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates. Conclusions Among patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation.