scholarly journals P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack

Stroke ◽  
2021 ◽  
Author(s):  
Zi-Xiao Li ◽  
Yunyun Xiong ◽  
Hong-Qiu Gu ◽  
Marc Fisher ◽  
Ying Xian ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
High Risk ◽  
Transient Ischemic Attack ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Controlled Trials ◽  
P2y12 Inhibitors ◽  
All Cause Mortality ◽  
Ischemic Attack

Background and purpose: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack. Methods: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I 2 test. Results: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68–0.83], I 2 =0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90–1.89], I 2 =0%), cardiovascular death (RR, 1.34 [95% CI, 0.56–3.17], I 2 =0%), mild bleeding (RR, 1.25 [95% CI, 0.37–4.29], I 2 =94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62–3.39], I 2 =0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16–4.08], I 2 =41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75–4.67], I 2 =0%) or ticagrelor (RR, 2.17 [95% CI, 1.16–4.08], I 2 =37%) but not within 21 days or clopidogrel. Conclusions: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.

scholarly journals Ticagrelor vs Clopidogrel in addition to Aspirin in minor ischemic stroke/ transient ischemic attack—Protocol for a systematic review and network meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250553
Author(s):  
Gabriele Zitikyte ◽  
Danielle Carole Roy ◽  
Shan Dhaliwal ◽  
Ronda Lun ◽  
Brian Hutton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
High Risk ◽  
Transient Ischemic Attack ◽  
Symptom Onset ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Minor Ischemic Stroke ◽  
Ischemic Attack

Introduction Patients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual antiplatelet therapy regimens—namely, Ticagrelor and Aspirin versus Clopidogrel and Aspirin. This systematic review and network meta-analysis (NMA) will examine the efficacy of these two different antiplatelet regimens in preventing recurrent stroke and mortality up to 30 days. Methods and analysis MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with the assistance of a medical information specialist. Two independent reviewers will screen studies for inclusion; eligible studies will include randomized controlled trials that enrolled adults presenting with acute minor ischemic stroke or transient ischemic attack and compared one or more of the interventions against each other and/or a control. The primary outcomes will be recurrent ischemic stroke up to 30 days from symptom onset. Secondary outcomes will include safety outcomes (I.e. major bleeding and mortality), functional disability, and outcomes up to 90 days from symptom onset. A Bayesian approach to NMA will be implemented using the BUGSnet function in R Software. Between group comparisons for time-to-event (TTE) and dichotomous outcomes will be presented in terms of hazard ratios and odds ratios with 95% credible intervals, respectively. Secondary effect measures of treatment ranking will also be estimated. Ethics and dissemination No formal research ethics approval are necessary. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will aid clinicians in decision-making on the choice of antithrombotic therapy in a high-risk stroke population and could be important in the development of future treatment trials and guidelines. Registration ID with Open Science Framework: 10.17605/OSF.IO/XDJYZ.

Clinical Effects of Dual Antiplatelet Therapy or Aspirin Monotherapy after Acute Minor Ischemic Stroke or Transient Ischemic Attack, a Meta-Analysis

2021 ◽  
Vol 27 ◽  
Author(s):  
Francesco Condello ◽  
Gaetano Liccardo ◽  
Giuseppe Ferrante
Keyword(s):  
Ischemic Stroke ◽  
Major Bleeding ◽  
Transient Ischemic Attack ◽  
Hemorrhagic Stroke ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Stroke Recurrence ◽  
Controlled Trials ◽  
Minor Ischemic Stroke ◽  
Ischemic Attack

Background: Evidence about the use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors in patients with acute minor ischemic stroke or transient ischemic attack (TIA) is emerging. The aim of our study was to provide an updated and comprehensive analysis about the risks and benefits of DAPT versus aspirin monotherapy in this setting. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov databases, main international conference proceedings were searched for randomized controlled trials comparing DAPT versus aspirin monotherapy in patients with acute ischemic stroke or TIA not eligible for thrombolysis or thrombectomy presenting in the first 24 hours after the acute event. Data were pooled by meta-analysis using a random-effects model. The primary efficacy endpoint was ischemic stroke recurrence, and the primary safety outcome was major bleeding. Secondary endpoints were intracranial hemorrhage, hemorrhagic stroke, and all-cause death. Results: A total of 4 studies enrolling 21,459 patients were included. DAPT with clopidogrel was used in 3 studies, DAPT with ticagrelor in one study. DAPT duration was 21 days in one study, 1 month in one study, and 3 months in the remaining studies. DAPT was associated with a significant reduction in the risk of ischemic stroke recurrence (relative risk [RR], 0.74; 95% confidence interval [CI], 0.67-0.82, P<0.001, number needed to treat 50 [95% CI 40-72], while it was associated with a significantly higher risk of major bleeding (RR, 2.59; 95% CI 1.49-4.53, P=0.001, number needed to harm 330 [95% CI 149-1111]), of intracranial hemorrhage (RR 3.06, 95% CI 1.41-6.66, P=0.005), with a trend towards higher risk of hemorrhagic stroke (RR 1.83, 95% CI 0.83-4.05, P=0.14), and a slight tendency towards higher risk of all-cause death (RR 1.30, 95% CI 0.89-1.89, P=0.16). Conclusions: Among patients with acute minor ischemic stroke or TIA, DAPT, as compared with aspirin monotherapy, might offer better effectiveness in terms of ischemic stroke recurrence at the expense of a higher risk of major bleeding. The trade-off between ischemic benefits and bleeding risks should be assessed in tailoring the therapeutic strategies.

Pioglitazone for the Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with or at High Risk of Type 2 Diabetes Mellitus: A Meta-Analysis

2019 ◽  
Vol 105 (5) ◽  
pp. 1670-1681 ◽  
Author(s):  
Yue Zhou ◽  
Yajing Huang ◽  
Xiaoyun Ji ◽  
Xiang Wang ◽  
Liyan Shen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
High Risk ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Primary And Secondary Prevention ◽  
All Cause Mortality ◽  
History Of

Abstract Context The goal of the meta-analysis was to evaluate the effect of pioglitazone on the primary and secondary prevention of cardiovascular diseases (CVDs) and renal adverse events in patients with or at high risk of type 2 diabetes mellitus (T2DM). Design Randomized controlled trials (RCTs) comparing pioglitazone with any control were identified through PubMed, Embase, and the Cochrane Library. Cardiovascular outcomes included major adverse cardiovascular events (MACEs, defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), hospitalization for heart failure, and all-cause mortality. Renal outcomes included change in urinary albumin to creatinine ratio and 24-hour urinary protein excretion. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence intervals (CIs) were pooled. Results A total of 26 studies with 19 645 participants were enrolled. Pioglitazone reduced the risk of MACE (RR, 0.8 [95% CI, 0.7–0.9]), with benefit only seen in patients with a history of established CVDs (0.8 [0.7–0.9]) and not in those without (1.0 [0.7–1.3]). Regarding the individual components, pioglitazone reduced the risk of nonfatal myocardial infarction (0.8 [0.6–1.0]) and nonfatal stroke (0.8 [0.7–0.9]), which was confined to patients with a history of established CVDs, whereas no treatment effect was found on cardiovascular death (1.0 [0.7–1.2]) regardless of the presence of established CVDs. Pioglitazone increased the risk of hospitalization for heart failure (1.3 [1.1–1.6]) and had no treatment effect on all-cause mortality (1.0 [0.8–1.1]). Pioglitazone reduced albuminuria by 18.5% (WMD 18.5% [95% CI, 21.1-16.0]), with a similar benefit in patients with different renal function categories. Conclusions Pioglitazone should be considered in patients with or at high risk of T2DM for the prevention of cardiovascular endpoints, especially in those with a history of established CVD who might benefit the most. Robust reductions in progression of renal disease are seen regardless of baseline renal function degree.

scholarly journals Optimal Duration of Aspirin Plus Clopidogrel After Ischemic Stroke or Transient Ischemic Attack

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 947-953 ◽  
Author(s):  
Hammad Rahman ◽  
Safi U. Khan ◽  
Fahad Nasir ◽  
Tehseen Hammad ◽  
Michael A. Meyer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Major Bleeding ◽  
Transient Ischemic Attack ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Controlled Trials ◽  
Short Term ◽  
All Cause Mortality ◽  
Ischemic Attack

Background and Purpose— The role of aspirin plus clopidogrel (A+C) therapy compared with aspirin monotherapy in patients presenting with acute ischemic stroke (IS) or transient ischemic attack remains uncertain. We conducted this study to determine the optimal period of efficacy and safety of A+C compared with aspirin monotherapy. Methods— Ten randomized controlled trials (15 434 patients) were selected using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) (inception June 2018) comparing A+C with aspirin monotherapy in patients with transient ischemic attack or IS. The primary efficacy outcome was recurrent IS, and the primary safety outcome was major bleeding. The secondary outcomes were major adverse cardiovascular events (composite of stroke, myocardial infarction, and cardiovascular mortality) and all-cause mortality. We stratified analysis based on the short- (≤1 month), intermediate- (≤3 month), and long-term (>3 month) A+C therapy. Effects were estimated as relative risk (RR) with 95% CI. Results— A+C significantly reduced the risk of recurrent IS at short-term (RR, 0.53; 95% CI, 0.37–0.78) and intermediate-term (RR, 0.72; 95% CI, 0.58–0.90) durations. Similarly, major adverse cardiovascular event was significantly reduced by short-term (RR, 0.68; 95% CI, 0.60–0.78) and intermediate-term (RR, 0.76; 95% CI, 0.61–0.94) A+C therapy. However, long-term A+C did not yield beneficial effect in terms of recurrent IS (RR, 0.81; 95% CI, 0.63–1.04) and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.71–1.07). Intermediate-term (RR, 2.58; 95% CI, 1.19–5.60) and long-term (RR, 1.87; 95% CI, 1.36–2.56) A+C regimens significantly increased the risk of major bleeding as opposed to short-term A+C (RR, 1.82; 95% CI, 0.91–3.62). Excessive all-cause mortality was limited to long-term A+C (RR, 1.45; 95% CI, 1.10–1.93). Conclusions— Short-term A+C is more effective and equally safe in comparison to aspirin alone in patients with acute IS or transient ischemic attack.

Abstract 16401: Duration of Dual Antiplatelet Therapy in Coronary Heart Disease: A 60,000-patient Meta-analysis of Randomised Controlled Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anda Bularga ◽  
Mohammed Meah ◽  
Dimitrios Doudesis ◽  
Anoop S Shah ◽  
Nicholas L Mills ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Major Bleeding ◽  
Randomised Controlled Trials ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Short Term ◽  
All Cause Mortality ◽  
Standard Duration ◽  
Randomised Controlled

Introduction: Dual antiplatelet therapy (DAPT) is the cornerstone of pharmacological treatment for patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention for stable coronary disease. Despite widespread use, the optimal duration of DAPT remains uncertain. We present an updated meta-analysis comparing outcomes in short-term DAPT (≤ 6 months) versus long-term DAPT (≥ 12 months). Methods: Four major databases were searched for randomised controlled trials of interest. The primary outcome was all-cause mortality. Secondary safety outcomes included any bleeding and major bleeding. Efficacy outcomes included cardiovascular death, myocardial infarction, stent thrombosis, coronary revascularization and thrombotic stroke. Further subgroup analysis stratified by index presentation and a sensitivity analysis to evaluate shorter duration DAPT (≤3 months) was performed. Results: Nineteen randomised controlled trials were included (n=60,879) of which 8 compared shorter duration DAPT (≤3 months) with standard duration (12 months) (n=38,036). Short-term DAPT was associated with an apparent modest increase in myocardial infarction (risk ratio [RR] 1.09; 95% confidence interval [CI], 0.98-1.22) with a major reduction in bleeding (RR 0.68; 95% CI, 0.55-0.83) for major bleeding and (RR 0.66; 95% CI, 0.56-0.77 for any bleeding) and an overall apparent reduction in all-cause mortality (RR 0.90; 95% CI 0.81-1.01). These associations persisted when comparing shorter duration DAPT to standard duration. Subgroup analysis of patients with stable disease or ACS identified no significant heterogenicity in efficacy, safety or mortality outcomes. Conclusion: In the largest meta-analysis to date comparing duration of DAPT, we show that short (≤ 6 months) and shorter (≤ 3 months) DAPT is associated with continuing trends for small reductions in all-cause mortality irrespective of index presentation.

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