Risk of recurrent stroke and antiplatelet choice in breakthrough stroke while on aspirin.
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SUBMITTER: Kim JT
PROVIDER: S-EPMC7541489 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Risk of recurrent stroke and antiplatelet choice in breakthrough stroke while on aspirin.
Kim Joon-Tae JT Kim Beom Joon BJ Park Jong-Moo JM Lee Soo Joo SJ Cha Jae-Kwan JK Park Tai Hwan TH Lee Kyung Bok KB Lee Jun J Hong Keun-Sik KS Lee Byung-Chul BC Kim Dong-Eog DE Choi Jay Chol JC Kwon Jee-Hyun JH Shin Dong-Ick DI Sohn Sung Il SI Lee Ji Sung JS Lee Juneyoung J Bae Hee-Joon HJ
Scientific reports 20201007 1
Uncertainty regarding an optimal antiplatelet regimen still exists in patients with breakthrough acute ischemic stroke (AIS) while on aspirin. This study provides an analysis of a prospective multicenter registry between April 2008 and April 2014. Eligible patients were on aspirin at the time of AIS and treated with antiplatelet regimens (aspirin, clopidogrel, or clopidogrel-aspirin). Potential factors associated with the choice of each antiplatelet regimen were explored and included a predictiv ...[more]
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Project description:BackgroundRecurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.MethodsIn this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.ResultsA total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).ConclusionsThe trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)
| S-EPMC2714259 | biostudies-literature
Project description:ObjectiveMany patients receiving dual antiplatelet therapy still had recurrent strokes. We aimed to identify factors associated with recurrent stroke at 90 days in patients receiving dual antiplatelet therapy in Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events trial.MethodsPatients with transient ischaemic attack or minor stroke receiving clopidogrel and aspirin in the trial were analysed in the study. The primary outcome was recurrent stroke within 90 days after the index event. Cox proportional hazard model with backward selection was used to identify factors associated with stroke.ResultsAmong 2584 patients, 212 (8.2%) had a recurrent stroke, 216 (8.4%) had a composite of stroke, myocardial infarction, or vascular death and 204 (7.9%) had ischaemic stroke within 90 days. Multivariate analysis identified the following factors associated with stroke: history of hypertension with poor blood pressure control (HR, 1.92; 95% CI 1.22 to 3.03), the high baseline National Institute of Health Stroke Scale (NIHSS) score of 2 and 3 (2.12 (1.07 to 4.21) and 4.11 (2.05 to 8.22), respectively), time from onset to randomisation of <12 hours (1.47 (1.12 to 1.94)), the lipid-lowering therapy (0.61 (0.47 to 0.83)), the open-label aspirin dose at day 1 of ≥300 mg (1.98 (1.45 to 2.69)). Intracranial arterial stenosis (ICAS) was significantly associated with stroke in the sensitivity analysis (2.17 (1.16 to 4.04)).ConclusionsThe high baseline NIHSS score, hypertension with poor blood pressure control, ICAS, time from onset to randomisation of less than 12 hours and no lipid-lowering therapy were associated with stroke, suggesting that patients with identified predictors still remain to be at high risk of recurrent stroke although being under the dual antiplatelet therapy.Trial registration numberhttp://clinicaltrials.gov/show/NCT00979589. ClinicalTrials.gov number: NCT00979589.
| S-EPMC5829906 | biostudies-literature
Project description:ObjectiveTo determine black-white differences in 1-year recurrent stroke and 30-day case fatality after a recurrent stroke in older US adults.MethodsWe conducted a retrospective cohort study using a 5% random sample of Medicare beneficiaries with fee-for-service health insurance coverage who were hospitalized for ischemic stroke between 1999 and 2013. Hazard ratios for recurrent ischemic stroke and risk ratios for 30-day case fatality comparing blacks to whites were calculated with adjustment for demographics, risk factors, and competing risk of death when appropriate.ResultsAmong 128,789 Medicare beneficiaries having an ischemic stroke (mean age 80 years [SD 8 years], 60.4% male), 11.1% were black. The incidence rate of recurrent ischemic stroke per 1,000 person-years for whites and blacks was 108 (95% confidence interval [CI], 106-111) and 154 (95% CI 147-162) , respectively. The multivariable-adjusted hazard ratio for recurrent stroke among blacks compared with whites was 1.36 (95% CI 1.29-1.44). The case fatality after recurrent stroke for blacks and whites was 21% (95% CI 21%-22%) and 16% (95% CI 15%-18%), respectively. The multivariable-adjusted relative risk for mortality within 30 days of a recurrent stroke among blacks compared with whites was 0.82 (95% CI 0.73-0.93).ConclusionThe risk of stroke recurrence among older Americans hospitalized for ischemic stroke is higher for blacks compared to whites, while 30-day case fatality after recurrent stroke remains lower for blacks.
| S-EPMC6251602 | biostudies-literature
Project description: Not available
| S-EPMC5321490 | biostudies-literature
Project description:BackgroundDual antiplatelet therapy using acetylsalicylic acid (ASA, aspirin) and clopidogrel is of great importance following coronary stenting. However, the variable platelet inhibitory effectiveness compromises the antithrombotic advantages provided by dual antiplatelet therapy. The aim of this single-center prospective study was to reduce the low response incidence of dual antiplatelet therapy with ASA and clopidogrel according to a prespecified therapy algorithm.MethodsPlatelet function testing using whole blood aggregometry (Chronolog 590) was performed 48 hours following coronary stenting (for either acute coronary syndromes or stable coronary artery disease) on 504 patients. The antiplatelet therapy included a loading dose of 600 mg clopidogrel and 500 mg ASA, followed by 75 mg clopidogrel and 100 mg ASA once daily. Clopidogrel low responders (CLR: >5 ohm; adenosine diphosphate (ADP) 5 μM) and/or ASA low responders (ALR: >0 ohm; arachidonic acid 10 μM) were treated according to a structured therapy plan: in the case of CLR, the maintenance + dose was doubled (repeated loading dose followed by 150 mg daily), and when still ineffective ticlopidine or prasugrel, if available and not contraindicated, were used. ALR was treated by increasing the dose to 300 mg in a first step or to 500 mg ASA when the first modification did not take effect sufficiently. In addition, ADP receptor antagonist 2-methylthioadenosine 5'-monophosphate triethylammonium salt (MeSAMP) testing and ASA incubation were performed to rule out either a platelet ADP-receptor defect or an ASA pharmacokinetic resistance.ResultsOf the total cohort of 504 patients, we detected 30.8% clopidogrel low-responders and 19.4% aspirin low-responders. For ALR, with a dose adjustment of 300 mg ASA daily, 94.6% of ALR were effectively treated and the residual 5.4% by administration of daily dosages of 500 mg ASA. This means that after modification of the ASA maintenance dose, all initial ALRs had an adequate antiplatelet response. The results for clopidogrel revealed that 69% of the CLR were treated effectively by increasing the clopidogrel dose to 150 mg daily. When prasugrel was not available or contraindicated, 12.7% of the remaining low responders showed an adequate result after being switched to ticlopidine. Consequently, by applying the therapy algorithm, we were able to reduce the CLR prevalence by 86.6%. On including prasugrel in the therapy plan, we were finally able to eliminate thienopyridine low response. In addition, no ADP receptor defect was found in this study as a potential reason for CLR. We identified the following factors associated with both CLR and ALR status: acute coronary syndromes, positive troponin values as well as diabetes mellitus and elevated HbA1C values and a higher platelet count. Furthermore, our data revealed for CLR elevated C-reactive protein values and a high PREDICT-score (including an age >65 years, acute coronary syndrome, diabetes mellitus, renal failure, and reduced left ventricular function) as risk factors. The following factors correlated with the risk of ASA low response: patients with elevated hemoglobin, serum creatinine and C-reactive protein values. In addition, medication with nitrates reduced the risk of being CLR. As also holds true for CLR, we found the PREDICT-score to be correlated to the risk of being ALR. However, by far the strongest risk factor for CLR or ALR was the fact of dual resistance.ConclusionFollowing a structured therapy plan based on a "test and treat" strategy, the prevalence of clopidogrel or aspirin low response can be significantly reduced and the risk of inadequate dual antiplatelet therapy minimized.
| S-EPMC3033359 | biostudies-literature
Project description:Although the exact prevalence of antiplatelet resistance in ischemic stroke is not known, estimates about the two most widely used antiplatelet agents - aspirin and clopidogrel - suggest that the resistance rate is high, irrespective of the definition used and parameters measured. Inadequate antiplatelet responsiveness correlates with an increased risk of recurrent ischemic vascular events in patients with stroke and acute coronary syndrome. It is not currently known whether tailoring antiplatelet therapy based on platelet function test results translates into a more effective strategy to prevent secondary vascular events after stroke. Large-scale clinical trials using a universally accepted definition and standardized measurement techniques for antiplatelet resistance are needed to demonstrate whether a 'platelet-function test-guided antiplatelet treatment' strategy translates into improved stroke care. This article gives an overview of the clinical importance of laboratory antiplatelet resistance, describes the challenges for platelet-function test-guided antiplatelet treatment and discusses practical issues about the management of patients with aspirin and/or clopidogrel resistance.
| S-EPMC3086673 | biostudies-literature
Project description:ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation.
| S-EPMC4256539 | biostudies-literature
Project description:BACKGROUND:Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population. METHODS:In a randomized trial, we assigned patients with minor ischemic stroke or high-risk TIA to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. The dose of aspirin in each group was selected by the site investigator. The primary efficacy outcome in a time-to-event analysis was the risk of a composite of major ischemic events, which was defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event, at 90 days. RESULTS:A total of 4881 patients were enrolled at 269 international sites. The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events and a higher risk of major hemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% confidence interval [CI], 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02). CONCLUSIONS:In patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone. (Funded by the National Institute of Neurological Disorders and Stroke; POINT ClinicalTrials.gov number, NCT00991029 .).
| S-EPMC6193486 | biostudies-literature
Project description:Stroke is one of the leading causes of disability and death. Ischemic stroke is a syndrome with heterogeneous mechanisms and multiple etiologies, rather than a singularly defined disease. Approximately one third of ischemic strokes are preceded by another cerebrovascular ischemic event. Stroke survivors are at high risk of vascular events (i.e., cerebrovascular and cardiovascular events), particularly during the first several months after the ischemic event. The use of antiplatelet agents remains the fundamental component of secondary stroke prevention. Based on the available data, antiplatelet agents should be used for patients with noncardioembolic stroke. The use of combination therapy (aspirin plus clopidogrel) has not been proven to be effective or safe to use for prevention of early stroke recurrence or in long-term treatment. There is no convincing evidence that any of the available antiplatelet agents are superior for a given stroke subtype. Currently, the uses of aspirin, clopidogrel, or aspirin combined with extended release dipyridamole are all valid alternatives after an ischemic stroke or transient ischemic attack. However, to maximize the effects of these agents, the treatment should be initiated as early as possible and be continued on a lifelong basis.
| S-EPMC3250274 | biostudies-literature
Project description:BackgroundThe significantly higher risk of primary stroke in Black vs. Whites is very well established. However, very few studies have specifically examined the presence of this racial disparity in recurrent stroke risk.MethodsWe conducted an analysis of a clinical trial dataset comprising 3470 recent non-cardioembolic stroke patients aged ≥35years and followed for 2years. Subjects were categorized by race into Whites and Blacks. Cox regression analysis was used to evaluate the associations between Black (vs. White) and ischemic stroke (primary outcome); and stroke/coronary heart disease (CHD)/vascular death as major vascular events (secondary outcome) with and without adjustment for comorbid conditions associated with stroke.ResultsAmong participants (2925 Whites and 545 Blacks), a total of 287 (8.3%) incident stroke and 582 (16.8%) major vascular events occurred. Compared with Whites, Blacks had higher frequencies of prior stroke, hypertension, diabetes mellitus, and smoking; but were younger with lower prevalence of CHD. Frequency of stroke was higher in Blacks vs. Whites (11.4% vs. 7.7%; P=0.004), but there was no difference in major vascular events (16.9% vs. 16.8%). Compared with Whites, Blacks experienced a significantly higher risk of recurrent stroke (HR 1.58; 95% CI, 1.19-2.09), but the stroke risk was not significant after multivariable adjustment (1.13; 0.81-1.59).ConclusionBlacks are ~60% more likely to experience a recurrent stroke within 2years than their Whites, but this risk is likely mediated via stroke risk factors. These results underscore a need to optimize and sustain risk factor control in Black stroke populations.
| S-EPMC4876018 | biostudies-literature