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 ◽  
...  

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.

Stroke ◽  
2021 ◽  
Author(s):  
Kirtipal Bhatia ◽  
Vardhmaan Jain ◽  
Devika Aggarwal ◽  
Muthiah Vaduganathan ◽  
Sameer Arora ◽  
...  

Background and Purpose: Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke. Methods: We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model. Results: Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68–0.83]; P <0.001; I 2 = 0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14–4.34], P =0.02, I 2 = 46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69–0.84], P <0.001, I 2 = 0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67–0.82], P <0.001, I 2 = 0%). Conclusions: As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.


2021 ◽  
Vol 27 ◽  
Author(s):  
Francesco Condello ◽  
Gaetano Liccardo ◽  
Giuseppe Ferrante

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.


Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3531-3540
Author(s):  
Michael Ouk ◽  
Che-Yuan Wu ◽  
Jessica Colby-Milley ◽  
Jiming Fang ◽  
Limei Zhou ◽  
...  

Background and Purpose: Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression. Methods: Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003–2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke. Results: Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X 2 =5.4; P =0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHR Depression =1.57 [1.24–1.98]) and incident dementia (aHR Depression =1.85 [1.40–2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHR Diabetes =1.20 [1.12–1.29]; aHR Depression =1.19 [1.04–1.37]), incident dementia (aHR Diabetes =1.14 [1.06–1.23]; aHR Depression =1.27 [1.08–1.49]), stroke/transient ischemic attack readmission (aHR Diabetes =1.18 [1.10–1.26]; aHR Depression =1.24 [1.07–1.42]), and all-cause mortality (aHR Diabetes =1.29 [1.23–1.36]; aHR Depression =1.16 [1.05–1.29]). Conclusions: The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.


Stroke ◽  
2010 ◽  
Vol 41 (2) ◽  
pp. 239-243 ◽  
Author(s):  
Evan L. Thacker ◽  
Kerri L. Wiggins ◽  
Kenneth M. Rice ◽  
W.T. Longstreth ◽  
Joshua C. Bis ◽  
...  

Stroke ◽  
2021 ◽  
Author(s):  
Zi-Xiao Li ◽  
Yunyun Xiong ◽  
Hong-Qiu Gu ◽  
Marc Fisher ◽  
Ying Xian ◽  
...  

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.


2020 ◽  
Vol 49 (5) ◽  
pp. 474-480
Author(s):  
Minyoul Baik ◽  
Hyo Suk Nam ◽  
Ji Hoe Heo ◽  
Hyung Jong Park ◽  
Beom Kyung Kim ◽  
...  

<b><i>Introduction:</i></b> There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA). <b><i>Objective:</i></b> We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA. <b><i>Methods:</i></b> This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of &#x3e;3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used. <b><i>Results:</i></b> There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40–6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59–12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05–3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037). <b><i>Conclusions:</i></b> The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA.


Stroke ◽  
2021 ◽  
Author(s):  
Takao Hoshino ◽  
Kentaro Ishizuka ◽  
Sono Toi ◽  
Takafumi Mizuno ◽  
Ayako Nishimura ◽  
...  

Background and Purpose: Notwithstanding the current guideline-based management, patients with stroke retain a substantial risk of further vascular events. We aimed to assess the contribution of atherogenic dyslipidemia (AD) to this residual risk. Methods: This was a prospective observational study, in which 792 patients (mean age, 70.1 years; male, 60.2%) with acute ischemic stroke (n=710) or transient ischemic attack (n=82) within 1 week of onset were consecutively enrolled and followed for 1 year. AD was defined as having both elevated levels of triglycerides ≥150 mg/dL and low HDL-C (high-density lipoprotein cholesterol) <40 mg/dL in men or <50 mg/dL in women, under fasting conditions. The primary outcome was a composite of major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death. Results: The prevalence of AD was 12.2%. Patients with AD more often had intracranial artery stenosis than those without (42.3% versus 24.1%; P =0.004), whereas no differences were observed in the prevalence of extracranial artery stenosis (17.7% versus 12.9%; P =0.62) or aortic plaques (33.3% versus 27.0%; P =0.87). At 1 year, patients with AD were at a greater risk of major adverse cardiovascular events (annual rate, 24.5% versus 10.6%; hazard ratio [95% CI], 2.33 [1.44–3.80]) and ischemic stroke (annual rate, 16.8% versus 8.6%; hazard ratio [95% CI], 1.84 [1.04–3.26]) than those without AD. When patients were stratified according to baseline LDL-C (low-density lipoprotein cholesterol) level, AD was predictive of major adverse cardiovascular events among those with LDL-C ≥100 mg/dL (n=509; annual rate, 20.5% versus 9.6%; P =0.036) as well as those with LDL-C <100 mg/dL (n=283; annual rate, 38.6% versus 12.4%; P <0.001). Conclusions: AD is associated with intracranial artery atherosclerosis and a high residual vascular risk after a stroke or transient ischemic attack. AD should be a promising modifiable target for secondary stroke prevention. REGISTRATION: URL: https://upload.umin.ac.jp ; Unique identifier: UMIN000031913.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anda Bularga ◽  
Mohammed Meah ◽  
Dimitrios Doudesis ◽  
Anoop S Shah ◽  
Nicholas L Mills ◽  
...  

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.


Stroke ◽  
2019 ◽  
Vol 50 (11) ◽  
pp. 3135-3140 ◽  
Author(s):  
Dimitrios Sagris ◽  
Georgios Georgiopoulos ◽  
Kalliopi Perlepe ◽  
Konstantinos Pateras ◽  
Eleni Korompoki ◽  
...  

Background and Purpose— It is unclear whether treatment with anticoagulants or antiplatelets is the optimal strategy in patients with stroke or transient ischemic attack of undetermined cause and patent foramen ovale that is not percutaneously closed. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare anticoagulant or antiplatelet treatment in this population. Methods— We searched PubMed until July 16, 2019 for trials comparing anticoagulants and antiplatelet treatment in patients with stroke/transient ischemic attack and medically treated patent foramen ovale using the terms: “cryptogenic or embolic stroke of undetermined source” and “stroke or cerebrovascular accident or transient ischemic attack” and “patent foramen ovale or patent foramen ovale or paradoxical embolism” and “trial or study” and “antithrombotic or anticoagulant or antiplatelet.” The outcomes assessed were stroke recurrence, major bleeding, and the composite end point of stroke recurrence or major bleeding. We used 3 random-effects models: (1) a reference model based on the inverse variance method with the Sidik and Jonkman heterogeneity estimator; (2) a strict model, implementing the Hartung and Knapp method; and (3) a commonly used Bayesian model with a prior that assumes moderate to large between-study variance. Results— Among 112 articles identified in the literature search, 5 randomized controlled trials were included in the meta-analysis (1720 patients, mean follow-up 2.3±0.5 years). Stroke recurrence occurred at a rate of 1.73 per 100 patient-years in anticoagulant-assigned patients and 2.39 in antiplatelet-assigned patients (hazard ratio, 0.68; 95% CI, 0.32–1.48 for the Sidik and Jonkman estimator). Major bleeding occurred at a rate of 1.16 per 100 patient-years in anticoagulant-assigned patients and 0.68 in antiplatelet-assigned patients (hazard ratio, 1.61; 95% CI, 0.72–3.59 for the Sidik and Jonkman estimator). The composite outcome occurred in 52 anticoagulant-assigned and 54 antiplatelet-assigned patients (odds ratio, 1.05; 95% CI, 0.65–1.70 for the Sidik and Jonkman estimator). Conclusions— We cannot exclude a large reduction of stroke recurrence in anticoagulant-assigned patients compared with antiplatelet-assigned, without significant differences in major bleeding. An adequately powered randomized controlled trial of a non–vitamin K antagonist versus aspirin is warranted.


Sign in / Sign up

Export Citation Format

Share Document