Abstract WP424: Efficacy Of Antiplatelet Therapy For Secondary Stroke Prevention Following Lacunar Stroke: A Meta-analysis And Pooled Analysis Of Randomized Controlled Trials

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ashkan Shoamanesh ◽  
Chun Shing Kwok ◽  
Phyo K Myint ◽  
Yoon K Loke ◽  
Hannah Copley ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Lacunar Stroke ◽  
Stroke Patients

INTRODUCTION: The predominant underlying mechanism of lacunar stroke differs from that of other ischemic stroke subtypes. Accordingly, so may the ideal stroke prevention regimen. We aimed to evaluate the efficacy of different antiplatelet agents in lacunar stroke patients. Method: We searched MEDLINE, EMBASE and the Cochrane library for RCTs that evaluated antiplatelet therapy in patients with ischemic stroke. Trials which provided stroke recurrence rates in patients presenting with lacunar stroke, or where the data was obtainable from manuscript authors were included. In addition, we included the novel SPS3 trial’s antiplatelet arm data presented at the 2011 ISC. We performed pooled analysis to assess the crude frequency of recurrent stroke and a random effects meta-analysis. Results: Lacunar stroke data was available for 12 trials encompassing 35, 218 participants (mean age 65, 65% male). The pooled crude recurrent stroke rate was least for cilostazol monotherapy (6.2%), followed by ASA monotherapy (7.4%), clopidogrel monotherapy (8.6%), ASA/dipyridamole (8.6%) and greatest for ASA/clopidogrel therapy (9.1%). Rate ratios of lacunar stroke patients suggest no significant efficacy advantage for ASA [ASA vs placebo (RR 0.72, 95% CI 0.34-1.50; p=0.38)], ASA/clopidogrel [ASA/clopidogrel vs ASA (RR 0.80, 95% CI 0.62-1.03; p=0.08), ASA/clopidogrel vs clopidogrel (RR 0.95, 95% CI 0.79-1.15; p=0.63)], sarpogrelate [sarpogrelate vs ASA (RR 1.31, 95% CI 0.84-2.04; p=0.23)] and ASA/dipyridamole [ASA/dipyridamole vs ASA (RR 0.90, 95% CI 0.70-1.16; p=0.042)] for recurrent stroke. The results from Japanese trials evaluating the efficacy of cilostazol found that it is significantly better than both placebo (RR 0.51, 95% CI 0.30-0.85; p=0.01) and ASA (RR 0.70, 95% CI 0.51-0.96; p=0.03) in the secondary prevention of stroke. Conclusions: There seems to be no significant advantage among the various antiplatelet agents studied in lacunar stroke patients apart for cilostazol. However, this requires confirmation within large randomized trials outside of Japanese populations.

Meta-analysis of the Smoker’s Paradox in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment

2019 ◽  
Vol 21 (9) ◽  
pp. 1181-1188 ◽  
Author(s):  
Peng Zhang ◽  
Zhen-Ni Guo ◽  
Xin Sun ◽  
Yingkai Zhao ◽  
Yi Yang
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Functional Outcomes ◽  
Meta Analysis ◽  
Intravenous Thrombolysis ◽  
Cochrane Library ◽  
Stroke Patients ◽  
Good Functional Outcome

Abstract Introduction The existence of the smoker’s paradox is controversial and potential mechanisms have not been explained. We aimed to explore the association between cigarette smoking and functional outcome at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis (IVT) or endovascular treatment (EVT). Methods This meta-analysis was conducted in accordance with the PRISMA guidelines. Studies exploring the association between smoking and good functional outcome (modified Rankin Scale score ≤ 2) following IVT or EVT were searched via the databases of PubMed, Embase, and the Cochrane Library from inception to August 8, 2018. Information on the characteristics of included studies was independently extracted by two investigators. Data were pooled using a random-effects or fixed-effects meta-analysis according to the heterogeneity of included studies. Results Among 20 identified studies, 15 reported functional outcomes following IVT, and five reported functional outcomes following EVT. Unadjusted analyses showed that smoking increased the odds of good functional outcomes with a pooled odds ratio (OR) of 1.48 (95% confidence interval [CI]: 1.36–1.60) after IVT and 2.10 (95% CI: 1.47–3.20) after EVT. Of IVT studies, only eight reported outcomes adjusted for covariates and none of the EVT studies reported adjusted outcomes. After adjustment, the relation between smoking and good functional outcome following IVT lost statistical significance (OR 1.14 [95% CI: 0.81–1.59]). Conclusion Our meta-analysis suggested that smoking was not associated with good functional outcome (mRS ≤ 2) at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis. Implications The existence of the smoker’s paradox is controversial. A previous letter by Plas et al. published in 2013 reported a positive result for the association between smoking and good functional outcome at 3 months in acute ischemic stroke patients who received intravenous thrombolysis (IVT). However, a major limitation of their meta-analysis was that the process of data synthesis was based on unadjusted data. Therefore, we conducted this meta-analysis to investigate the association based on adjusted data and a larger sample size. Our meta-analysis suggested that smoking was not associated with good functional outcome after adjusting for covariates.

Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale

Stroke ◽  
2021 ◽  
Author(s):  
Hans-Christoph Diener ◽  
Aurauma Chutinet ◽  
J. Donald Easton ◽  
Christopher B. Granger ◽  
Eva Kleine ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Patent Foramen Ovale ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Dabigatran Etexilate ◽  
Embolic Stroke ◽  
Thrombin Inhibitor ◽  
Foramen Ovale ◽  
Significant Difference

Background and Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43–1.14]) for ischemic stroke. Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.

Abstract W P374: Population-Based Eligibility for a Stroke Prevention Trial Evaluating Novel Anticoagulants and Embolic Strokes of Uncertain Etiology: Similar Eligibility as for IV Rt-PA

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Dawn Kleindorfer ◽  
Scott Kasner ◽  
Charles J Moomaw ◽  
Kathleen Alwell ◽  
Opeolu Adeoye ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Cryptogenic Stroke ◽  
Population Based ◽  
Vascular Imaging ◽  
Stroke Patients ◽  
Exclusion Criteria ◽  
The Us ◽  
Uncertain Etiology

Introduction: The RESPECT-ESUS trial is proposed to evaluate the best stroke prevention strategy for patients with strokes of uncertain etiology. This trial will compare a novel anticoagulant with antiplatelet agents to prevent recurrent stroke among cryptogenic stroke patients. We sought to evaluate the eligibility for this trial within a large, biracial population representative of the US. Methods: All adult ischemic stroke patients in 2010 among residents of the 5-county Greater Cincinnati/Northern Kentucky region (population 1.3 million) were ascertained from all local hospitals via ICD-9 codes 430-436. Inclusion and exclusion criteria supplied by the corporate sponsor as of 6/30/14 were applied to the ischemic stroke population. Per trial protocol, a complete workup was defined as brain and both intra- and extracranial vascular imaging, ECHO, telemetry, and EKG. Results: Of 1894 ischemic stroke patients without hemorrhagic transformation who survived the hospital stay (and not sent to hospice), 138 (7.4%) would have been eligible for RESPECT-ESUS. Inclusion and exclusion criteria are listed in the Table. If we were to assume that every stroke patient received a complete workup and no further etiologies were identified, the “hypothetical” eligibility could be as high as 18.7%. Discussion: We found that the potential eligibility for the RESPECT-ESUS trial to be low, and in fact is similar to population-based estimates of rt-PA eligibility (6%-8%). Extrapolation of eligibility across the US would be further limited by presentation to an enrolling center and consent refusal rates. Our estimates are based on information obtained during hospitalization, which may over- or underestimate eligibility within the 3-6 month post-event enrollment window. It is likely that centers that participate in the trial will have more complete diagnostic workups, which was a major exclusion in our population, especially the requirement for intracranial vascular imaging.

scholarly journals WMH and long-term outcomes in ischemic stroke

Neurology ◽  
2019 ◽  
Vol 92 (12) ◽  
pp. e1298-e1308 ◽  
Author(s):  
Marios K. Georgakis ◽  
Marco Duering ◽  
Joanna M. Wardlaw ◽  
Martin Dichgans
Keyword(s):  
Ischemic Stroke ◽  
Functional Impairment ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Stroke Recurrence ◽  
Stroke Severity ◽  
Stroke Patients ◽  
Increased Risk

ObjectiveTo investigate the relationship between baseline white matter hyperintensities (WMH) in patients with ischemic stroke and long-term risk of dementia, functional impairment, recurrent stroke, and mortality.MethodsFollowing the Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42018092857), we systematically searched Medline and Scopus for cohort studies of ischemic stroke patients examining whether MRI- or CT-assessed WMH at baseline are associated with dementia, functional impairment, recurrent stroke, and mortality at 3 months or later poststroke. We extracted data and evaluated study quality with the Newcastle–Ottawa scale. We pooled relative risks (RR) for the presence and severity of WMH using random-effects models.ResultsWe included 104 studies with 71,298 ischemic stroke patients. Moderate/severe WMH at baseline were associated with increased risk of dementia (RR 2.17, 95% confidence interval [CI] 1.72–2.73), cognitive impairment (RR 2.29, 95% CI 1.48–3.54), functional impairment (RR 2.21, 95% CI 1.83–2.67), any recurrent stroke (RR 1.65, 95% CI 1.36–2.01), recurrent ischemic stroke (RR 1.90, 95% CI 1.26–2.88), all-cause mortality (RR 1.72, 95% CI 1.47–2.01), and cardiovascular mortality (RR 2.02, 95% CI 1.44–2.83). The associations followed dose-response patterns for WMH severity and were consistent for both MRI- and CT-defined WMH. The results remained stable in sensitivity analyses adjusting for age, stroke severity, and cardiovascular risk factors, in analyses of studies scoring high in quality, and in analyses adjusted for publication bias.ConclusionsPresence and severity of WMH are associated with substantially increased risk of dementia, functional impairment, stroke recurrence, and mortality after ischemic stroke. WMH may aid clinical prognostication and the planning of future clinical trials.

scholarly journals Factors Affecting Non-Adherence to Secondary Stroke Prevention Therapy in Ischemic Stroke Patients

2018 ◽  
Vol 8 (2) ◽  
pp. 90
Author(s):  
Zakky Cholisoh ◽  
Hidayah Karuniawati ◽  
Tanti Azizah ◽  
Zaenab Zaenab ◽  
Laila Nur Hekmah
Keyword(s):  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Antihypertensive Agents ◽  
Heart Association ◽  
Secondary Stroke Prevention ◽  
Stroke Patients ◽  
Factors Affecting ◽  
Prevention Therapy

Stroke is cardiovascular disease that causes the world's highest disability and is the most prevalence disease after heart disease and cancer. Stroke is caused by circulatory disorders with 80% of the sufferers are diagnosed with ischemic stroke and 20% of them are diagnosed with hemorrhagic stroke. Patients who survive from the first stroke have high risk to have recurrent stroke. American Heart Association/American Stroke Association and Perhimpunan Dokter Spesialis Syaraf Indonesia recommend secondary stroke prevention therapy including antiplatelet/anticoagulant, antihypertensive agents, and antidislipidemia to minimalize the risk of recurrent stroke. Secondary stroke prevention therapy is only the first step. Patients need to be adhere to those therapies. The non-adherence will increase the risk of recurrent stroke. The study aimed to determine factors which causing the non-adherence to secondary prevention therapy in patients with ischemic stroke. This was a case control study with concecutive sampling method by interviewing patients who met the inclusion criterias i.e., had been diagnosed and were inpatients due to ischemic stroke, but in the time of interview patients were outpatients, patients were able to communicate and agree to participate in the study.Data was analized by bivariate / chi square test and multivariate logistic regression test. During the study period, 184 respondents met the inclusion criterias. Factors affecting non-adherence in the use of secondary prevention therapy were No one reminded to take medicine p = 0.03; OR 4.51, denial of the disease p = 0,036 OR 214, and tired of taking medicine p = 0,045 OR 1,97.

scholarly journals Network Meta-Analysis of Ticagrelor for Stroke Prevention in Patients at High Risk for Cardiovascular or Cerebrovascular Events

Stroke ◽  
2021 ◽  
Author(s):  
Alexandra Bálint ◽  
Dániel Tornyos ◽  
Oumaima El Alaoui El Abdallaoui ◽  
Péter Kupó ◽  
András Komócsi
Keyword(s):  
Acute Coronary Syndrome ◽  
Ischemic Stroke ◽  
High Risk ◽  
Risk Ratio ◽  
Stroke Prevention ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Coronary Syndrome ◽  
Artery Disease

Background and Purpose: Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease. Methods: Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality. Results: Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71–0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77–1.00]; P =0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91–1.07]). Conclusions: Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.

scholarly journals Oral Anticoagulant and Antiplatelet Therapy for Cervical Artery Dissection: A Meta-Analysis of Clinical Trials

2021 ◽  
Vol 27 ◽  
pp. 107602962110517
Author(s):  
Sheng-Lin Ye ◽  
Chuang Wang ◽  
Lu-Lu Wang ◽  
Tian-Ze Xu ◽  
Xiao-Qiang Li ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Vertebral Artery ◽  
Antiplatelet Therapy ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
Artery Dissection ◽  
Cervical Artery Dissection ◽  
Curative Effect ◽  
Ischemic Attack

Carotid and vertebral artery dissections are estimated to account for ∼20% of strokes in patients under 45-years-old. This meta-analysis compared the efficacy and safety of treatment with anticoagulants versus antiplatelet agents to determine the optimal therapy. We searched 4 electronic databases for clinical trials published from January 1, 1980 to August 25, 2021 that included patients who received anticoagulant or antiplatelet therapy for carotid and/or vertebral artery dissections. The curative effect was judged by recanalization evaluated by imaging. The primary outcomes were all cause death and ischemic stroke; secondary outcomes included hemorrhage and transient ischemic attack (TIA). Patients who received only a single drug treatment were divided into antiplatelet or anticoagulant groups; all received conservative treatment without surgical intervention. For this investigation, we pooled the available studies to conduct a meta-analysis, which included 7 articles with 1126 patients. The curative effect of vascular recanalization was not significantly different between the 2 treatment groups (odds ratio [OR] = 0.913, 95% confidence interval [CI]: 0.611-1.365, P = .657); similarly, no significant differences were found regarding the primary outcomes all cause death (OR = 1.747, 95%CI: 0.202-15.079, P = .612) and ischemic stroke (OR = 2.289, 95%CI: 0.997-5.254, P = .051). Patients treated with anticoagulants were more likely to experience TIA (OR = 0.517, 95%CI: 0.252-1.060, P = .072) and hemorrhage (OR = 0.468, 95%CI: 0.210-1.042, P = .063), but the differences were not statistically significant. Overall, there were no statistically significant differences between anticoagulant therapy and antiplatelet therapy for the treatment of carotid and vertebral artery dissections.

scholarly journals Safety and Efficacy of Thrombolysis in Cervical Artery Dissection-Related Ischemic Stroke: A Meta-Analysis of Observational Studies

2016 ◽  
Vol 42 (3-4) ◽  
pp. 272-279 ◽  
Author(s):  
Jueying Lin ◽  
Yefei Sun ◽  
Shanshan Zhao ◽  
Junjie Xu ◽  
Chuansheng Zhao
Keyword(s):  
Ischemic Stroke ◽  
Observational Studies ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Artery Dissection ◽  
Cervical Artery Dissection ◽  
Stroke Patients ◽  
Safety And Efficacy ◽  
Excellent Outcome ◽  
Cervical Artery

Background: Although thrombolysis is considered to be the first-line treatment for ischemic stroke, there remains an ongoing controversy on the safety and efficacy of thrombolysis in cervical artery dissection (CAD). The aim of this meta-analysis was to assess observational data related to the safety and efficacy of thrombolysis in CAD-related ischemic stroke. Methods: We performed a systematic search of the efficacy of thrombolysis treatment in CAD-related ischemic stroke with appropriate observational studies identified for the study. The meta-analysis models in Comprehensive Meta-Analysis V2 software were applied to calculate the merged rates of favorable outcome (modified Rankin Scale, mRS 0-2), excellent outcome (mRS 0-1), intracranial hemorrhage (ICH), symptomatic ICH (SICH), mortality and recurrent stroke between thrombolysis and non-thrombolysis in CAD-related stroke. The difference of outcomes and adverse events between the 2 groups was compared by analyzing the pooled OR value and chi-square test using the software SPSS. Results: A total of 846 patients were identified from 10 studies (174 with thrombolysis; 672 with non-thrombolysis). The meta-analysis detected no significant statistical difference in the proportion of CAD-related stroke patients enjoying a favorable outcome at the 3 months' follow-up between the thrombolysis and non-thrombolysis groups (53.7 vs. 58.2%, OR 0.782, χ2 = 0.594, p > 0.05); non-thrombolysis was slightly superior than thrombolysis in terms of excellent outcome (52.4 vs. 34.4%, OR 0.489, χ2 = 9.143, p = 0.002). There was no significant difference in SICH, mortality and recurrent stroke rates between the 2 groups (all p > 0.05). ICH rate was higher in the thrombolysis group of CAD-related stroke patients compared to that in the non-thrombolysis group (12.3 vs. 7.4%, OR 2.647, χ2 = 4.127, p = 0.042). Conclusion: Thrombolysis seems to be equally safe and will achieve an efficacy similar to the efficacy of non-thrombolysis in patients with acute ischemic stroke due to CAD. It is also as effective as thrombolysis in stroke from miscellaneous causes. Therefore, CAD patients experiencing a stroke should not be denied thrombolysis therapy. However, this will need to be confirmed in large-scale randomized studies, especially involving intravenous thrombolysis treatment.

scholarly journals New oral anticoagulants combined with antiplatelet therapy in the treatment of coronary heart disease: an updated meta-analysis

2020 ◽  
Author(s):  
Leiling Liu ◽  
Jiahui Hu ◽  
Yating Wang ◽  
Hao Lei ◽  
Danyan Xu
Keyword(s):  
Ischemic Stroke ◽  
Combination Therapy ◽  
Antiplatelet Therapy ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Cochrane Library ◽  
Coronary Syndrome ◽  
Stable Cad

Abstract Objective New oral anticoagulants (NOACs) combined with antiplatelet therapy for acute coronary syndrome (ACS) may reduce ischemic events, but there is no consensus on bleeding risk. Moreover, the effect of NOACs on stable coronary artery disease (CAD) needs to be elucidated. We conducted a meta-analysis, to summarize the efficacy and safety of NOACs combined with antiplatelet therapy in the treatment of stable CAD and ACS.Methods We searched PubMed, Web of Science, and the Cochrane Library, then performed a systematic review of all 17 randomized controlled trials.Results For patients with stable CAD, rivaroxaban combined with antiplatelet therapy significantly reduced the rate of major adverse cardiovascular events (MACEs) (risk ratio; 95% confidence interval: 0.88; 0.81–0.95) and ischemic stroke (0.62; 0.50–0.77), with a relatively low risk of major bleeding (1.72; 1.42–2.07). For patients with ACS, the combination of NOACs could reduce the risk of MACEs (0.91; 0.85–0.97), myocardial infarction (MI) (0.90; 0.83–0.98) and ischemic stroke (0.75; 0.58–0.97), accompanied by increased non–fatal bleeding events and intracranial hemorrhage (3.42; 1.76–6.65). Results were similar when restricting the analysis to phase III studies except for the rate of stroke in patients with ACS.Conclusions Combination therapy can reduce the incidence of MI in ACS patients, but the risk of bleeding from intracranial hemorrhaging outweighs the benefit of MACEs driven by MI. That is due to combination therapy having no positive impact on mortality, thus the benefit-risk balance may be more favorable with patients with stable CAD.

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