Anticoagulation With or Without Antiplatelet Therapy Following Transcatheter Aortic Valve Replacement for Patients With Atrial Fibrillation: A Meta-Analysis

BackgroundAlthough current guidelines recommend oral anticoagulants (OAC) with or without antiplatelet therapy (APT) following transcatheter aortic valve replacement (TVAR) in patients with an indication for long-term anticoagulation therapy, the optimal antithrombotic strategy remains unknown in these population. Herein, we conducted a meta-analysis comparing the outcome of OAC alone versus OAC with APT following TAVR in patients with atrial fibrillation (AF).MethodsMEDLINE and EMBASE were searched through May 2020 to identify clinical trials that investigated OAC alone versus OAC with APT following TAVR in patients with AF. From each study, we extracted the hazard ratios (HRs) or risk ratios of major or life threatening bleeding, stroke, all-cause mortality and cardiovascular mortality.Results1 randomized controlled trial and 3 observational studies were identified, which enrolled a total of 2032 patients with AF who underwent TAVR assigned to the OAC group (n = 722) or OAC with APT group (n = 1310). Pooled analyses demonstrated the rate of major or life threatening bleeding was significantly lower in the OAC group compared to the OAC with APT group (HR [95% Confidence Interval [CI] = 0.54 [0.38–0.77], P = .0006]). However, the rate of stroke was similar in both groups (HR [95% CI] = 1.22 [0.80–1.87], P = .36). All-cause and cardiovascular mortalities were also similar in both groups.ConclusionsWe observed that OAC with APT following TAVR in patients with AF increased the risk of bleeding compared to OAC alone without decreasing the risk of stroke.     

Secondary prevention of cryptogenic stroke in patients with patent foramen ovale: a systematic review and meta-analysis

The aim of our study is to compare patent foramen ovale (PFO) closure versus medical treatment and antiplatelet versus anticoagulant therapy in patients with cryptogenic stroke (CS) and PFO. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) of randomized trials. Primary outcomes are stroke or transient ischemic attack (TIA) and all-cause mortality. Secondary outcomes are peripheral embolism, bleeding, serious adverse events, myocardial infarction and atrial dysrhythmias. We performed an intention to treat meta-analysis with a random-effects model. We include six trials (3677 patients, mean age 47.3 years, 55.8% men). PFO closure is associated with a lower recurrence of stroke or TIA at a mean follow-up of 3.88 years compared to medical therapy [risk ratio (RR) 0.55, 95% CI 0.38–0.81; I²?=?40%]. The TSA confirms this result. No difference is found in mortality (RR 0.74, 95% CI 0.35–1.60; I²?=?0%), while PFO closure is associated with a higher incidence of atrial dysrhythmias (RR 4.55, 95% CI 2.16–9.60; I²?=?25%). The rate of the other outcomes is not different among the two groups. The comparison between anticoagulant and antiplatelet therapy shows no difference in terms of stroke recurrence, mortality and bleeding. There is conclusive evidence that PFO closure reduces the recurrence of stroke or TIA in patients younger than 60 years of age with CS. More data are warranted to assess the consequences of the increase in atrial dysrhythmias and the advantage of PFO closure over anticoagulants.     

Antithrombotic Therapy and Cardiovascular Outcomes After Transcatheter Aortic Valve Replacement in Patients With Atrial Fibrillation

ObjectivesThe study sought to determine the patterns of antithrombotic therapy and association with clinical outcomes in patients with atrial fibrillation (AF) and 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 ≥2 following transcatheter aortic valve replacement (TAVR).BackgroundThe impact of antithrombotic regimens on clinical outcomes in patients with AF and severe aortic stenosis treated with TAVR is unknown.MethodsIn the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and associated registries, 1,621 patients with prior AF and CHA₂DS₂-VASc score ≥2 comprised the study cohort. Outcomes were analyzed according to antithrombotic therapy.ResultsDuring the 5-year enrollment period, 933 (57.6%) patients were discharged on oral anticoagulant therapy (OAC). Uninterrupted antiplatelet therapy (APT) for at least 6 months or until an endpoint event was used in 544 of 933 (58.3%) of patients on OAC and 77.5% of patients not on OAC. At 2 years, patients on OAC had a similar rate of stroke (6.6% vs. 5.6%; p = 0.53) and the composite outcome of death or stroke (29.7% vs. 31.8%; p = 0.33), compared with no OAC. OAC with APT was associated with a reduced rate of stroke (5.4% vs. 11.1%; p = 0.03) and death or stroke (29.7% vs. 40.1%; p = 0.01), compared with no OAC or APT. Following adjustment, OAC with APT and APT alone were both associated with reduced rates of stroke compared with no OAC or APT (hazard ratio for OAC+APT: 0.43, 95% confidence interval: 0.22 to 0.85; p = 0.015; hazard ratio for APT alone: 0.32, 95% confidence interval: 0.16 to 0.65; p = 0.002), while OAC alone was not.ConclusionsAmong patients with prior AF undergoing TAVR, antiplatelet with or without anticoagulant therapy was associated with a reduced risk of stroke at 2 years, implicating multifactorial stroke mechanisms in this population.     

Safety and efficacy of anticoagulant monotherapy in atrial fibrillation and stable coronary artery disease: A systematic review and meta-analysis

BackgroundAdjunctive use of oral anticoagulant (OAC) and antiplatelet therapy (APT) in patients with stable coronary artery disease (CAD) and nonvalvular atrial fibrillation (AF) is a challenge of daily practice.MethodsA comprehensive literature search of databases was performed to identify studies comparing the safety and efficacy of OAC monotherapy and combined therapy (OAC plus single (S) APT). Events including major adverse cardiovascular events (MACE), all-cause mortality, stroke and major bleeding were analyzed.ResultsSeven articles comprising 11,070 subjects were identified. Combined therapy was associated with a significantly higher risk of major bleeding (pooled hazard ratio (HR) of 1.62, 95% CI 1.40–1.86, p=<0.0001) compared to the OAC monotherapy. There was no significant difference between the two comparison arms in terms of MACE (HR 1.14; 95% CI 0.97–1.34, p = 0.11), stroke (HR 1.05; 95% CI 0.77–1.43, p = 0.78) and all-cause mortality (HR 1.15; 95% CI 0.94–1.40, p = 0.16). Stratified analysis by inclusion of only patients with coronary stents attenuated the safety effect of monotherapy. Subgroup analysis based on the study design, type of OAC, major bleeding criteria and APT revealed findings consistent with the pooled HR. The combined therapy group had a 19% and 38% higher risk of MACE in studies with a history of MI (p = 0.03) and with the use of rivaroxaban (p = 0.02), respectively.ConclusionOAC monotherapy might have a lower incidence of major bleeding events with no higher overall risk of MACE, ischemic stroke and all-cause mortality compared to the combined therapy group.     

Antithrombotic Therapy With or Without Aspirin After Percutaneous Coronary Intervention or Acute Coronary Syndrome in Patients Taking Oral Anticoagulation: A Meta-Analysis and Network Analysis of Randomized Controlled Trials

IntroductionTrials investigating aspirin omission in patients taking oral anticoagulation (OAC) after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) were not powered to assess rates of major bleeding or ischemic events.MethodsWe performed an updated meta-analysis and network analysis of randomized trials comparing treatment with or without aspirin in patients taking OAC and a P2Y12-inhibitor after PCI or ACS. The primary outcome was TIMI major bleeding.ResultsFive trials enrolling 11,542 patients allocated to antithrombotic regimens omitting (n = 5795) or including aspirin (n = 5747) were included. Aspirin omission was associated with a lower risk of TIMI major bleeding (RR = 0.56, 95% CI [0.44–0.71]; P < 0.001) but a trend towards a higher risk of MI (RR = 1.21, 95% CI [0.99–1.47]; P = 0.06), which was significantly higher when only non-vitamin K antagonist OAC (NOAC)-based trials were considered (P_interaction = 0.02). The risk of stent thrombosis was comparable with both strategies (RR = 1.29, 95% CI [0.87–1.90]; P = 0.20), with a trend towards a higher risk of ST with aspirin omission when only NOAC-based trials were considered (P_interaction = 0.06). Risks of stroke and death were similar with both strategies. Network meta-analysis ranked dabigatran (low dose) without aspirin as the best strategy for bleeding reduction (P-score = 0.86) and apixaban with aspirin as the best strategy for MI reduction (P-score = 0.66).ConclusionsIn patients taking OAC after PCI or ACS, aspirin omission is associated with a lower risk of TIMI major bleeding, with a numerically increased risk of MI, which is statistically significant when only NOAC-based trials are considered. This supports individualization of the treatment regimen based on patient risk.     

Propensity-Matched Comparison of Oral Anticoagulation Versus Antiplatelet Therapy After Left Atrial Appendage Closure With WATCHMAN

ObjectivesIn this propensity-matched analysis of post–left atrial appendage closure antithrombotic therapy, the safety and effectiveness of oral anticoagulation (OAC) and antiplatelet therapy (APT) were compared.BackgroundLeft atrial appendage closure with the WATCHMAN device is an alternative to OAC in patients with nonvalvular atrial fibrillation, who are at high bleeding risk. Initial trials included 45 days of post-implantation OAC, but registry data suggest that APT may suffice.MethodsPatients from the PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), CAP (Continued Access to PROTECT-AF), CAP2 (Continued Access to PREVAIL), ASAP (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology), and EWOLUTION (Registry on WATCHMAN Outcomes in Real-Life Utilization) trials receiving either OAC or APT post-implantation were matched and compared for nonprocedural bleeding and stroke or systemic thromboembolism over 6 months following implantation. Each patient on APT was matched with 2 patients on OAC, with propensity scores derived from age, sex, congestive heart failure, hypertension, diabetes, prior transient ischemic attack or stroke, peripheral vascular disease, left ventricular ejection fraction, renal impairment, and different atrial fibrillation subtypes.ResultsThe cohort on OAC (n = 1,018; 95% receiving warfarin and 5% receiving nonwarfarin OAC) was prescribed 45-day OAC post-implantation (92% also received single APT), followed by 6-month single or dual APT. The cohort on APT (n = 509; 91% receiving dual APT and 9% receiving single APT) received APT for variable durations. Six-month freedom from nonprocedural major bleeding was similar (OAC, 95.7%; APT, 95.5%; p = 0.775) despite more early bleeds with OAC. Freedom from thromboembolism beyond 7 days was similar between groups (OAC, 98.8%; APT, 99.4%; p = 0.089). However, device-related thrombosis was more frequent with APT (OAC, 1.4%; APT, 3.1%; p = 0.018).ConclusionsAfter left atrial appendage closure with the WATCHMAN, although device-related thrombosis was more common with APT, both APT and OAC strategies resulted in similar safety and efficacy endpoints.     

Impact of renal function in high bleeding risk patients undergoing percutaneous coronary intervention: a patient-level stratified analysis from four post-approval studies

Background

Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established.

Objective

We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF.

Methods

An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users.

Results

The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24).

Conclusions

In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

     

Atrial Septal Aneurysm,Shunt Size,and Recurrent Stroke Risk in Patients With Patent Foramen Ovale

BackgroundIn patients with patent foramen ovale (PFO)–associated stroke, the presence of large shunt or atrial septal aneurysm (ASA) has been suggested to convey a high risk of stroke recurrence.ObjectivesThe purpose of this study was to assess the respective influence of PFO size and ASA status on stroke recurrence under medical therapy in patients with recent PFO-associated stroke without alternative cause.MethodsThe authors pooled individual patient data from 2 prospective observational studies and the medical arms of 2 randomized trials, in which shunt size and ASA status was assessed by independent reading of echocardiographic images. Associations between PFO anatomical features and recurrent ischemic stroke were assessed by mixed effects Cox models.ResultsOf 898 patients (mean age 45.3 years), 178 (19.8%) had ASA with large PFO, 71 (7.9%) ASA with nonlarge PFO, 397 (44.2%) large PFO without ASA, and 252 (28.1%) nonlarge PFO without ASA. Over a median follow-up of 3.8 years (interquartile range: 2.6 to 5.5 years), 47 (5.2%) patients experienced a recurrent stroke. There was a heterogeneity across studies for the association between PFO size and stroke recurrence (p_interaction = 0.01). In a model accounting for age, hypertension, antithrombotic therapy, and PFO anatomy, ASA was independently associated with recurrent stroke (adjusted hazard ratio: 3.27; 95% confidence interval: 1.82 to 5.86; p < 0.0001), whereas large PFO was not (average adjusted hazard ratio across studies: 1.43; 95% confidence interval: 0.50 to 4.03; p = 0.50).ConclusionsIn patients with PFO-associated stroke, ASA is a more important predictor of recurrent stroke than shunt size. These results can help to better identify those patients with a high risk of stroke recurrence under medical therapy who may derive the most benefit from PFO closure. (Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence [CLOSE]; NCT00562289) (Device Closure versus Medical Therapy in Patients with Cryptogenic Stroke and High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)     

Patent Foramen Ovale Attributable Cryptogenic Embolism With Thrombophilia Has Higher Risk for Recurrence and Responds to Closure

ObjectivesThe aim of this study was to investigate the effect of management on the risk for recurrent events among patients with cryptogenic ischemic stroke or transient ischemic attack.BackgroundThe combination of patent foramen ovale (PFO) and hypercoagulability may greatly increase the risk for paradoxical embolism. However, previous randomized controlled trials evaluating the efficacy of PFO closure excluded these potential high-risk patients.MethodsPatients diagnosed with PFO attributable cryptogenic embolism were prospectively, without randomization, recruited from January 2005 to March 2018. The relationship between thrombophilia and recurrent events was evaluated in overall patients. Multivariate Cox regression was conducted to assess the relative risk for recurrence in PFO closure and medical therapy groups.ResultsA total of 591 patients with cryptogenic embolism with PFO were identified. The median duration of follow-up was 53 months, and thrombophilia significantly increased the risk for recurrent events (hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.09 to 3.16; p = 0.024). PFO closure was superior to medical therapy in overall patients (HR: 0.16; 95% CI: 0.09 to 0.30; p < 0.001). Of the 134 patients (22.7%) with thrombophilia, there was a difference in the risk for recurrence events between the PFO closure (6 of 89) and medical therapy (15 of 45) groups (HR: 0.25; 95% CI: 0.08 to 0.74; p = 0.012). There was no potential heterogeneity in the further subgroup analysis.ConclusionsPatients with cryptogenic stroke with PFO and hypercoagulable state had increased risk for recurrent stroke or transient ischemic attack. PFO closure provided a lower risk for recurrent events compared with medical therapy alone.     

Percutaneous Closure of Patent Foramen Ovale in Patients with Cryptogenic Stroke — An Updated Comprehensive Meta-Analysis

BackgroundThe ideal treatment strategy for patients with cryptogenic stroke and patent foramen ovale (PFO) is not yet clear. Previous randomized controlled trials (RCTs) comparing transcatheter PFO closure with medical therapy in patients with cryptogenic stroke to prevent recurrent ischemic stroke showed mixed results. This meta-analysis aims to compare rates of recurrent stroke, transient ischemic attack (TIA) and all-cause mortality with PFO closure and medical therapy vs. medical therapy alone.MethodsPubMed and the Cochrane Center Register of Controlled Trials were searched for studies published through June 2018, comparing PFO closure plus medical therapy versus medical therapy alone. Six RCTs (n = 3750) comparing PFO closure with medical therapy were included in the analysis. End points were recurrent stroke, TIA and all-cause mortality. The odds ratios (OR) with 95% confidence interval (CI) were computed and p < 0.05 was considered as a level of significance.ResultsA total of 1889 patients were assigned to PFO closure plus medical therapy and 1861 patients were assigned to medical therapy only. Risk of recurrent stroke was significantly lower in the PFO closure plus medical therapy group compared to medical therapy alone. (OR 0.47, 95% CI 0.33–0.67, p < 0.0001). Rate of TIA was similar between the two groups (OR 0.76, 95% CI 0.52–1.14), p = 0.18). There was no difference in all-cause mortality between two groups (OR 0.73, CI 0.33–1.58, p = 0.42). Patients undergoing PFO closure were more likely to develop transient atrial fibrillation than medical therapy alone (OR: 5.85; CI: 3.06–11.18, p ≤0.0001) whereas the risk of bleeding was similar between the groups (OR: 0.93; CI: 0.55–1.57, p = 0.78).ConclusionsThe results of this meta-analysis suggest that transcatheter closure of PFO plus medical therapy is superior to medical therapy alone for the prevention of recurrent cryptogenic stroke. However, PFO closure in these patients has not been shown to reduce the risk of recurrent TIA or all-cause mortality. There is a higher rate of transient atrial fibrillation post PFO closure device placement, the long-term effects of which have yet to be studied.     

Patent Foramen Ovale Closure vs Medical Therapy for Stroke Prevention: Meta-analysis of Randomized Trials and Review of Heterogeneity in Meta-analyses

Background

Patent foramen ovale (PFO) might be a risk factor for unexplained (“cryptogenic”) stroke or transient ischemic attack (TIA). We sought to determine the efficacy and safety of transcatheter PFO closure compared with antithrombotic therapy for secondary prevention of cerebrovascular events among patients with cryptogenic stroke.

Methods

We performed a systematic review and meta-analysis of MedLine and Embase (from inception to March 2013) for randomized controlled trials (RCTs) that compared transcatheter PFO closure with medical therapy in subjects with cryptogenic stroke. Data were independently extracted on trial conduct quality, baseline characteristics, efficacy, and safety events from published articles and appendices. Risk ratios (RRs) and 95% confidence intervals (CIs) for the composite of stroke or TIA, and adverse cardiovascular events including atrial fibrillation/flutter were constructed.

Results

Three RCTs of 2303 subjects with previous stroke, TIA, or systemic arterial embolism (mean age, 45.7 years; 47.3% women; mean follow-up, 2.6 years) were included. PFO closure did not significantly reduce the risk of recurrent stroke/TIA (3.7% vs 5.2%; RR, 0.73; 95% CI, 0.50-1.07; P = 0.10); however, an increased risk of incident atrial fibrillation/flutter was detected (3.8% vs 1.0%; RR, 3.67; 95% CI, 1.95-6.89; P < 0.0001). No significant heterogeneity was detected for any end point among subgroups of patients stratified according to age, sex, index cardiovascular event, device type, interatrial shunt size, and presence of an atrial septal aneurysm (all P interactions ≥ 0.09).

Conclusions

Meta-analysis of RCTs that assessed transcatheter PFO closure for secondary prevention of cerebrovascular events in subjects with cryptogenic stroke does not demonstrate benefit compared with antithrombotic therapy, and suggests potential risks.     

Effect of anticoagulation on cardioembolic stroke severity,outcomes and response to intravenous thrombolysis

Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010–2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5–1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR <1.5 group, 13.3 % to the INR 1.5–1.9 and 10.5 % to the INR >2. 35 %of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95 % CI 1.006–4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173–3.789) as well as INR 1.5–1.9 (OR 3.676, 95 % CI 1.510–8.946) were associated with favorable outcomes (mRS ≤2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT.     

Subclinical Leaflet Thrombosis After Transcatheter Aortic Valve Replacement: A Meta-Analysis

This meta-analysis and systematic review was performed to evaluate the clinical relevance of subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement. PubMed, Web of Science, and CENTRAL were searched for eligible randomized and nonrandomized studies until November 2020. Risk ratios (RRs) or odds ratios and 95% CIs were calculated, using a random-effects model. Overall, 25 studies were eligible for the analysis and comprised a total of 11,098 patients. The median incidence of SLT was 6% at a median follow-up of 30 days. Use of intra-annular valves was associated with 2-fold greater risk for the development of SLT compared with use of supra-annular valves. There was no difference in the risk for SLT (RR: 0.97; 95% CI: 0.72-1.29; P = 0.83) between single-antiplatelet therapy (SAPT) and dual-antiplatelet therapy (DAPT), whereas oral anticoagulation (OAC) was associated with a 58% relative risk reduction for SLT (RR: 0.42; 95% CI: 0.29-0.61; P < 0.00001) compared with SAPT and DAPT. In patients with diagnosed leaflet thrombosis at follow-up, the risk for stroke or transient ischemic attack was increased by 2.6-fold (RR: 2.56; 95% CI: 1.60-4.09; P < 0.00001) compared with patients without leaflet thrombosis. In patients diagnosed with SLT, the odds of SLT resolution increased by 99% after switch from antiplatelet agents to OAC (odds ratio: 0.01; 95% CI: 0.00-0.06; P < 0.00001). To summarize, indication-based use of OAC after transcatheter aortic valve replacement is associated with a lower risk for SLT compared with SAPT and DAPT. Switching to OAC seems to be effective for SLT resolution. As SLT increased the odds of stroke or transient ischemic attack in the included population, further studies are needed to investigate whether screening tests for SLT and appropriate antithrombotic therapy improve long-term valve functionality and clinical prognosis.     

The association between sleep duration,napping, and stroke stratified by self-health status among Chinese people over 65 years old from the China health and retirement longitudinal study

Purpose

Stroke is a major cause of death in China. This study aimed to investigate the association between sleep duration (nighttime sleep and daytime napping) and stroke in elderly Chinese individuals with self-reported health status.

Methods

A total of 4785 Chinese adults over 65 years from the 2011 China Health and Retirement Longitudinal Study (CHARLS) were included. Binary logistic regression was used to estimate odds ratios and 95% confidence intervals of the association between sleep duration and stroke stratified by self-reported health status.

Results

A significant association between short sleep duration (< 7 h per day) and the risk of stroke (aOR?=?2.05; 95% CI 1.31–3.19), after controlling for sociodemographic characteristics, lifestyle factors, health status, and comorbidities. There was no significant association between short and long sleep duration and stroke in the individuals who reported good general health status. However, in individuals who reported poor health status, short sleep duration (aOR?=?2.11; 95% CI 1.30–3.44) and long sleep duration (aOR?=?1.86; 95% CI 1.08–3.21) were significantly associated with increased risk of stroke, compared with normal sleep duration (7–8 h per day). Disability was significantly associated with stroke in both self-reported good and poor health groups. Rural residence was significantly associated with a lower risk of stroke among individuals who reported poor health status.

Conclusions

Both short and long sleep duration were significantly associated with stroke among individuals who reported poor health. Stroke prevention should be focused on elderly individuals who believe that they have health problems.

     

Meta-Analysis of Secondary Prevention of Cryptogenic Stroke

BackgroundCryptogenic stroke and embolic stroke of undetermined source (ESUS) are a frequently encountered categories of ischemic stroke with an uncertain cause.MethodsWe analyzed all randomized clinical trials (RCTs) that evaluated antithrombotic therapy and patent foramen ovale (PFO) closure in cryptogenic stroke and/or ESUS. We calculated aggregate hazard ratios (HRs) using direct and network meta-analysis. The primary outcome was recurrent ischemic stroke.ResultsTen RCTs with a total of 16,876 patients, randomizing 32,143 patient-years of follow-up (mean age 61.2 ± 13.5 with 39.2% female) were identified. Anticoagulation therapy was associated with significantly reduced recurrent ischemic stroke compared with antiplatelet therapy (HR = 0.66; [95% confidence interval (CI) = 0.47–0.94]). Meta-regression analysis showed significantly reduced recurrent stroke with longer duration of therapy, and significantly increased events with advanced age. Significant interactions were observed based on the presence of PFO, stroke type, and anticoagulant used. There were no significant differences with regard to the composite ischemic outcome, transient ischemic attack, any death, major bleeding, or intracranial bleeding. In the network meta-analysis, compared to antiplatelet therapy, warfarin (HR = 0.31; [95% credible interval (CrI) = 0.12–0.68]) and PFO closure (HR = 0.14; 95% CrI = 0.05–0.31]) were associated with significantly reduced recurrent ischemic stroke. In rank order, PFO closure was associated with the best outcome, followed by warfarin.ConclusionsAmong patients with cryptogenic stroke, anticoagulation therapy, as compared with antiplatelet therapy is associated with lower rate of recurrent stroke. The small sample size and high heterogeneity with regards to bleeding outcomes require further large trials. In patients with PFO, closure and warfarin are associated with the lowest rates of recurrent stroke.     

Revascularization strategies in cardiogenic shock complicating acute myocardial infarction: A systematic review and meta-analysis

BackgroundThe optimal revascularization strategy in patients with multi-vessel disease (MVD) presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remains unclear.ObjectiveTo investigate the comparative differences between culprit-only revascularization (COR) versus instant multi-vessel revascularization (IMVR) in AMI and CS.Methods13 studies were selected using MEDLINE, EMBASE and the CENTRAL (Inception - 31 November2017). Outcomes were assessed at short-term (in-hospital or ≤30 days duration) and long-term duration (≥6 months). Estimates were reported as random effects relative risk (RR) with 95% confidence interval (CI).ResultsIn analysis of 7311 patients, COR significantly reduced the relative risk of short-term all-cause mortality (RR: 0.87; 95% CI, 0.77–0.97; p = 0.01, I² = 50%) and renal failure (RR: 0.75; 95% CI, 0.61–0.94; p = 0.01, I² = 7%) compared with IMVR. There were no significant differences between both the strategies in terms of reinfarction (RR: 1.25; 95% CI, 0.59–2.63; p = 0.56, I² = 0%), major bleeding (RR: 0.88; 95% CI, 0.75–1.04; p = 0.14, I² = 0%) and stroke (RR: 0.77; 95% CI, 0.50–1.17; p = 0.22, I² = 0%) at short term duration. Similarly, no significant differences were observed between both groups regarding all-cause mortality (RR; 1.01; 95% CI, 0.85–1.20; p = 0.93, I² = 61%) and reinfarction (RR: 0.71; 95% CI, 0.34–1.47; p = 0.35, I² = 26%) at long term duration.ConclusionIn MVD patients presenting with AMI and CS, IMVR was comparable to COR in terms of all-cause mortality at long term follow up duration. These results are predominantly derived from observational data and more randomized controlled trials are required to validate this impression.     

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BackgroundMany patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes.MethodsAdults with newly diagnosed atrial fibrillation and ≥ 1 investigator-defined stroke risk factor were enrolled in GARFIELD-AF between March 2010 and September 2015. The association between prior acute coronary syndromes and long-term outcomes was determined using a Cox proportional hazards model, adjusting for baseline risk factors, oral anticoagulation (OAC) ± antiplatelet (AP) therapy, and usual care.ResultsOf 39,679 patients, 10.5% had a history of acute coronary syndromes. At 2-year follow-up, patients with prior acute coronary syndromes had higher adjusted risks of stroke/systemic embolism (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.08-1.78), major bleeding (HR 1.30; 95% CI, 0.95 -1.79), all-cause mortality (HR 1.34; 95% CI, 1.21 -1.49), cardiovascular mortality (HR 1.85; 95% CI, 1.51-2.26), and new acute coronary syndromes (HR 3.42; 95% CI, 2.62-4.45). Comparing antithrombotic therapy in the acute coronary syndromes vs no acute coronary syndromes groups, most patients received OAC ± AP: 60.8% vs 66.1%, but AP therapy was more likely in the acute coronary syndromes group (68.1% vs 32.9%), either alone (34.9% vs 20.8%) or with OAC (33.2% vs 12.1%). Overall, 17.8% in the acute coronary syndromes group received dual AP therapy with (5.3%) or without OAC (12.5%). Among patients with moderate/high risk for stroke/systemic embolism, fewer in the acute coronary syndromes group received OAC with or without AP therapy (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category [CHA₂DS₂-VASc] 2: 52.1% vs 64.6%; CHA₂DS₂-VASc ≥ 3: 62.0% vs 70.7%), and the majority with a Hypertension (uncontrolled systolic blood pressure > 160 mm Hg), Abnormal renal or liver function, previous Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, and concomitant Drugs or alcohol excess (HAS-BLED) score ≥ 3 were on AP therapy (83.8% vs 65.5%).ConclusionsIn GARFIELD-AF, previous acute coronary syndromes are associated with worse 2-year outcomes and a greater likelihood of under-treatment with OAC, while two-thirds of patients receive AP therapy. Major bleeding was more common with previous acute coronary syndromes, even after adjusting for all risk factors.     

Safety of intravenous thrombolysis in stroke of unknown time of onset: A systematic review and meta-analysis

The safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke of unknown time of onset (SUTO) was unclear and mostly concerned. We sought to investigate the safety in terms of symptomatic intracranial hemorrhage (sICH) and death in SUTO patients treated with IV-tPA. We searched PubMed and EMBASE from inception to 2 December 2020 for eligible studies reporting IV-tPA in SUTO patients compared to conservative medical therapy, or to stroke of known onset time (SKOT) treated with IV-tPA within standard time window. We pooled relative risk (RR) with 95% confidence interval (95%CI) with random-effects model. Twenty-four studies were included, enrolling 77,398 patients. SUTO patients with IV-tPA had higher incidence of sICH than that in SUTO patients without IV-tPA (3.8% versus 0.96%; RR?=?3.75, 95%CI: 2.69–5.22) but comparable to that in SKOT patients with IV-tPA (3.8% versus 4.1%; RR?=?1.16, 95%CI: 0.94–1.44). There was no significant difference in death risk in SUTO patients with IV-tPA versus SUTO patients without IV-tPA (RR?=?1.34, 95%CI: 0.60–3.01) and versus SKOT patients with IV-tPA (RR?=?1.19, 95%CI: 0.95–1.50). Compared with SUTO patients without IV-tPA, SUTO patients with IV-tPA had higher likelihood of favorable functional outcome (adjusted RR?=?1.28, 95%CI: 1.03–1.60) and functional independence (adjusted RR?=?1.95, 95%CI: 1.24–3.06), comparable to that in SKOT patients with IV-tPA in favorable functional outcome (adjusted RR?=?0.67, 95%CI: 0.38–1.20) and functional independence (adjusted RR?=?0.84, 95%CI: 0.59–1.18). SUTO patients could be treated safely and effectively with IV-tPA under the guidance of imaging evaluation.

     

Efficacy and Safety of Low-Dose Prasugrel Versus Clopidogrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis

Purpose

To assess the efficacy and safety of low-dose prasugrel compared to clopidogrel based on the occurrence of major adverse cardiac events (MACEs) and major bleeding in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI).

Methods

The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were systematically searched up to May 2020 to identify relevant randomized controlled trials (RCTs) and observational studies. A meta-analysis was conducted using a random effects model to estimate relative risks (RRs) with 95% confidence intervals (CIs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively.

Results

Three RCTs (n?=?2884) and five observational studies (n?=?30,117) were included. A meta-analysis of RCTs revealed no significant differences in terms of MACE (RR 0.92, 95% CI 0.74 to 1.16) or major bleeding (RR 0.97, 95% CI 0.57 to 1.65) between low-dose prasugrel and clopidogrel. A meta-analysis of observational studies revealed no significant difference in terms of MACE (RR 1.13, 95% CI 0.82 to 1.55) between the two groups, but low-dose prasugrel was associated with a significantly increased risk of major bleeding (RR 1.33, 95% CI 1.02 to 1.72).

Conclusions

We found that low-dose prasugrel was not associated with changes in MACE or major bleeding compared with clopidogrel in RCTs. However, analysis of data from observational studies revealed that low-dose prasugrel was associated with an increased risk of major bleeding compared with clopidogrel.