Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke.
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ABSTRACT:
SUBMITTER: Hilkens NA
PROVIDER: S-EPMC8478107 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke.
Hilkens Nina A NA Algra Ale A Diener Hans Christoph HC Bath Philip M PM Csiba László L Hacke Werner W Kappelle L Jaap LJ Koudstaal Peter J PJ Leys Didier D Mas Jean-Louis JL Sacco Ralph L RL Greving Jacoba P JP
Stroke 20210726 10
<h4>Background and purpose</h4>Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk.<h4>Methods</h4>We pooled individual patient data from 6 randomized clinical trials (CAPRIE ...[more]
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Project description:Dual antiplatelet therapy simultaneously blocks different platelet activation pathways and might thus be more potent at inhibiting platelet activation and more effective at reducing major ischemic vascular events compared to antiplatelet monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. However, dual antiplatelet therapy carries an increased risk of bleeding. Patients with ischemic stroke or transient ischemic attack (TIA) are generally older and likely to have a fragile cerebrovascular bed, which further increases the risk of systemic major bleeding events and intracranial hemorrhage. Clinical trials and meta-analyses suggest that in comparison to antiplatelet monotherapy, dual antiplatelet therapy initiated early after noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent stroke and major vascular events without significantly increasing the rate of major bleeding events. In contrast, studies of long-term therapy in patients with noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding the benefit of dual antiplatelet therapy over monotherapy. However, the harm associated with major bleeding events, including intracranial hemorrhage, which is generally more disabling and more fatal than ischemic stroke, is likely to increase with dual antiplatelet therapy. Physicians should carefully assess the benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy when managing patients with ischemic stroke or TIA.
| S-EPMC4101094 | biostudies-literature
Project description:BackgroundThe latest guidelines do not make clear recommendations on the selection of antiplatelet therapies for long-term secondary prevention of stroke. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy and safety of long-term antiplatelet therapies after ischemic stroke or transient ischemic attack.Methods and resultsWe performed a network meta-analysis of randomized controlled trials to compare 11 antiplatelet therapies in patients with ischemic stroke or transient ischemic attack. In December 2014, we searched Medline, Embase, and the Cochrane Library database for trials. The search identified 24 randomized controlled trials including a total of 85 667 patients with antiplatelet treatments for at least 1 year. Cilostazol significantly reduced stroke recurrence in comparison with aspirin (odds ratio 0.66, 95% credible interval 0.44 to 0.92) and dipyridamole (odds ratio 0.57, 95% credible interval 0.34 to 0.95), respectively. Cilostazol also significantly reduced intracranial hemorrhage compared with aspirin, clopidogrel, terutroban, ticlopidine, aspirin plus clopidogrel, and aspirin plus dipyridamole. Aspirin plus clopidogrel could not significantly reduce stroke recurrence compared with monotherapies but caused significantly more major bleeding than all monotherapies except terutroban. The pooled estimates did not change materially in the sensitivity analyses of the primary efficacy outcome.ConclusionsLong-term monotherapy was a better choice than long-term dual therapy, and cilostazol had the best risk-benefit profile for long-term secondary prevention after stroke or transient ischemic attack. More randomized controlled trials in non-East Asian patients are needed to determine whether long-term use of cilostazol is the best option for the prevention of recurrent stroke.
| S-EPMC4599476 | biostudies-literature
Project description:BackgroundIt is still uncertain which antiplatelet regimen had the greatest net clinical benefit in patients who have suffered a transient ischemic attack or non-cardioembolic ischemic stroke, and it is necessary to choose the optimal regimen according to the clinical situation.MethodsWe utilized 3 databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials to find randomized controlled trials that met our criteria, and performed network meta-analyses in recurrent stroke, composite outcomes, major bleeding events, recurrent ischemic stroke, and all bleeding events. Three-dimensional clustered rank plots were used to obtain the net clinical benefit. Subgroup analyses were performed according to the symptom-onset-to-treatment time (<72 and >72 h), stroke subtypes (large artery atherosclerosis and small vessel occlusion), and dual antiplatelet agent treatment duration.ResultsA total of 69 trials were enrolled. Cilostazol was associated with a lower risk of recurrent stroke, major bleeding events, composite outcomes, recurrent ischemic stroke, and all bleeding events compared to low to medium dose aspirin. The three-dimensional rank plot showed that cilostazol had the highest net clinical benefit. The combination of aspirin plus clopidogrel had greater efficacy in the <72 h after stroke onset and large artery atherosclerosis subgroups, and when it was restricted to1 month of use major bleeding risk was not higher than aspirin. The combination of aspirin plus dipyridamole had greater efficacy and safety comparable to aspirin in terms of small vessel occlusion.ConclusionsThe efficacy and safety profiles among antiplatelet regimens may differ according to clinical situation, although cilostazol, aspirin plus clopidogrel, and aspirin plus dipyridamole may be considered as preferable options.
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Project description: Not available
| S-EPMC3134717 | biostudies-literature
Project description:BackgroundPatients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.MethodsIn this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.ResultsBy 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).ConclusionsIn this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).
| S-EPMC4887756 | biostudies-literature
Project description:ImportanceAccurate estimation of the association between transient ischemic attack (TIA) and risk of subsequent stroke can help to improve preventive efforts and limit the burden of stroke in the population.ObjectiveTo determine population-based incidence of TIA and the timing and long-term trends of stroke risk after TIA.Design, setting, and participantsRetrospective cohort study (Framingham Heart Study) of prospectively collected data of 14 059 participants with no history of TIA or stroke at baseline, followed up from 1948-December 31, 2017. A sample of TIA-free participants was matched to participants with first incident TIA on age and sex (ratio, 5:1).ExposuresCalendar time (TIA incidence calculation, time-trends analyses), TIA (matched longitudinal cohort).Main outcomes and measuresThe main outcomes were TIA incidence rates; proportion of stroke occurring after TIA in the short term (7, 30, and 90 days) vs the long term (>1-10 years); stroke after TIA vs stroke among matched control participants without TIA; and time trends of stroke risk at 90 days after TIA assessed in 3 epochs: 1954-1985, 1986-1999, and 2000-2017.ResultsAmong 14 059 participants during 66 years of follow-up (366 209 person-years), 435 experienced TIA (229 women; mean age, 73.47 [SD, 11.48] years and 206 men; mean age, 70.10 [SD, 10.64] years) and were matched to 2175 control participants without TIA. The estimated incidence rate of TIA was 1.19/1000 person-years. Over a median of 8.86 years of follow-up after TIA, 130 participants (29.5%) had a stroke; 28 strokes (21.5%) occurred within 7 days, 40 (30.8%) occurred within 30 days, 51 (39.2%) occurred within 90 days, and 63 (48.5%) occurred more than 1 year after the index TIA; median time to stroke was 1.64 (interquartile range, 0.07-6.6) years. The age- and sex-adjusted cumulative 10-year hazard of incident stroke for patients with TIA (130 strokes among 435 cases) was 0.46 (95% CI, 0.39-0.55) and for matched control participants without TIA (165 strokes among 2175) was 0.09 (95% CI, 0.08-0.11); fully adjusted hazard ratio [HR], 4.37 (95% CI, 3.30-5.71; P < .001). Compared with the 90-day stroke risk after TIA in 1948-1985 (16.7%; 26 strokes among 155 patients with TIA), the risk between 1986-1999 was 11.1% (18 strokes among 162 patients) and between 2000-2017 was 5.9% (7 strokes among 118 patients). Compared with the first epoch, the HR for 90-day risk of stroke in the second epoch was 0.60 (95% CI, 0.33-1.12) and in the third epoch was 0.32 (95% CI, 0.14-0.75) (P = .005 for trend).Conclusions and relevanceIn this population-based cohort study from 1948-2017, the estimated crude TIA incidence was 1.19/1000 person-years, the risk of stroke was significantly greater after TIA compared with matched control participants who did not have TIA, and the risk of stroke after TIA was significantly lower in the most recent epoch from 2000-2017 compared with an earlier period from 1948-1985.
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Project description:Background: Clopidogrel is frequently used in patients with ischemic stroke or transient ischemic attack (TIA), but its efficacy is hampered by inter-individual variability, due to genetic differences associated with clopidogrel metabolism. We conducted this randomized controlled trial to validate whether the personalized antiplatelet therapy based on clopidogrel pharmacogenomics and clinical characteristics leads to better clinical outcomes compared with standard treatment. Methods: Patients were randomly divided into the standard group or pharmacogenetic group, in which the pharmacogenetic group required the detection of the genotyping of CYP2C19*2, CYP2C19*3, and CYP2C19*17. Patients were followed up for 90 days for the primary efficacy endpoint of new stroke events, secondary efficacy endpoint of individual or composite outcomes of the new clinical vascular events, and the incidence of disability. The primary safety outcome was major bleeding. Results: A total of 650 patients underwent randomization, among which 325 were in the pharmacogenomics group while 325 were in the standard group. Our study found after a 90-day follow-up, the risk of stroke and composite vascular events in the pharmacogenomics group was lower than that in the standard group. The incidence of disability significantly decreased in the pharmacogenomics group. In addition, no statistically significant differences were observed in bleeding events between the two groups. Conclusion: The present study demonstrates that personalized antiplatelet therapy guided by clopidogrel pharmacogenomics and clinical characteristics can significantly improve the net clinical benefit of ischemic stroke or TIA patients during the 90-day treatment period without increasing bleeding risk.
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Project description:ObjectiveTo discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones.MethodsMetabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited <24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort.ResultsMetabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (<3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described.ConclusionsThe use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases.
| S-EPMC4336096 | biostudies-literature
Project description:BackgroundAntiplatelet drugs may prevent recurrent ischemic events after ischemic stroke but their relative effectiveness and harms still need to be clarified. Within this network meta-analysis we aimed to summarize the current evidence for using antiplatelet drugs for secondary stroke prevention.MethodsWe searched MEDLINE, EMBASE and CENTRAL up to September 2020. Randomized controlled trials (RCTs) assessing antiplatelet drugs for secondary stroke prevention were included. We did pairwise meta-analyses and network meta-analyses using random-effects models. Primary outcomes were all strokes (ischemic or hemorrhagic) and all-cause mortality.ResultsThe review included 57 RCTs, 50 (n = 165,533 participants) provided data for the meta-analyses. Compared to placebo/no treatment, moderate to high-confidence evidence indicated that cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day significantly reduced the risk of all strokes (odds ratios, ORs and absolute risk difference, ARD): cilostazol 0.51 (95 % confidence interval, CI, 0.37 to 0.71; 3.6 % fewer), clopidogrel 0.63 (95 % CI, 0.49 to 0.79; 2.7 % fewer), dipyridamole + aspirin 0.65 (95 % CI, 0.55 to 0.78; 2.5 % fewer), ticagrelor 0.68 (95 % CI, 0.50 to 0.93; 2.3 % fewer), ticlopidine 0.74 (95 % CI 0.59 to 0.93; 1.9 % fewer), aspirin ≤ 150 mg/day 0.79 (95 % CI, 0.66 to 0.95; 1.5 % fewer). Aspirin > 150 mg/day and the combinations clopidogrel/aspirin, ticagrelor/aspirin, also decrease all strokes but increase the risk of hemorrhagic events. Only aspirin > 150 mg/day significantly reduced all-cause mortality (OR 0.86, 95 % CI 0.76 to 0.97; ARD 0.9 %, 95 %CI 1.5-0.2 % fewer, moderate confidence). Compared to aspirin ≤ 150 mg/day, clopidogrel significantly reduced the risk of all strokes, cardiovascular events, and intracranial hemorrhage outcomes. Cilostazol also appeared to provide advantages but data are limited to the Asian population.ConclusionsConsidering the benefits and harms ratio, cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day appear to be the best choices as antiplatelet drugs for secondary prevention of patients with ischemic stroke or TIA.Systematic review registrationPROSPERO CRD42020159896 .
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Project description:A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA.
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