Showing papers by "J. Donald Easton published in 2018"
TL;DR: 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 ofMajor hemorrhage at 90 days than those who receive aspirin alone.
Abstract: 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 en...
735 citations
TL;DR: In this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction.
Abstract: Background and Purpose— SOCRATES (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), comparing ticagrelor with aspirin in patients with acute cerebral ischemia, found a nonsignificant 11% relative risk reduction for stroke, myocardial infarction, or death ( P =0.07). Aspirin intake before randomization could enhance the effect of ticagrelor by conferring dual antiplatelet effect during a high-risk period for subsequent stroke. Therefore, we explored the efficacy and safety of ticagrelor versus aspirin in the patients who received any aspirin the week before randomization. Methods— A prespecified subgroup analysis in SOCRATES (n=13 199), randomizing patients with acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤5) or transient ischemic attack (ABCD 2 score of ≥4) to 90-day treatment with ticagrelor or aspirin. Patients in the prior-aspirin group had received any aspirin within the week before randomization. Primary end point was time to stroke, myocardial infarction, or death. Safety end point was PLATO (Study of Platelet Inhibition and Patient Outcomes) major bleeding. Results— The 4232 patients in the prior-aspirin group were older, had more vascular risk factors, and vascular disease than the other patients. In the prior-aspirin group, the primary end point occurred in 138/2130 (6.5%) of patients on ticagrelor and in 177/2102 (8.3%) on aspirin (hazard ratio, 0.76; 95% confidence interval, 0.61–0.95; P =0.02); in patients with no prior-aspirin usage an event occurred in 304/4459 (6.9%) and 320/4508 (7.1%) on ticagrelor and aspirin, respectively (hazard ratio, 0.96; 95% confidence interval, 0.82–1.12; P =0.59). The treatment-by-prior-aspirin interaction was not statistically significant ( P =0.10). In the prior-aspirin group, major bleeding occurred in 0.7% and 0.4% of patients on ticagrelor and aspirin, respectively (hazard ratio, 1.58; 95% confidence interval, 0.68–3.65; P =0.28). Conclusions— In this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction. A new study will investigate the benefit-risk of combining ticagrelor and aspirin in patients with acute cerebral ischemia (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429). Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01994720.
18 citations
TL;DR: NOACs add to the therapeutic options for secondary stroke prevention in patients with AF and offer advantages over warfarin including a favorable bleeding profile and convenience of use.
Abstract: INTRODUCTION In patients with atrial fibrillation (AF), oral anticoagulation with vitamin K antagonists (VKA) (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention with a 60-70% relative reduction in stroke risk compared with placebo. Mortality is reduced by 26%. VKA have a number of well-documented shortcomings which were overcome by non-vitamin-K oral anticoagulants (NOACs). Areas covered: Results of randomized trials for four NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) have been published (ARISTOTLE, RE-LY, ENGAGE, ROCKET-AF). In this review, the authors discuss the results in subgroups of patients with prior transient ischemic attacks or ischemic stroke. In aggregate, the NOACs are superior to warfarin for secondary prevention and result in a 50% reduction in intracerebral hemorrhage. Apixaban was superior to aspirin in the AVERROES trial and had a similar rate of major bleeding complications. Expert opinion: NOACs add to the therapeutic options for secondary stroke prevention in patients with AF and offer advantages over warfarin including a favorable bleeding profile and convenience of use. Aspirin should no longer be used for secondary stroke prevention in patients with AF.
14 citations
TL;DR: Thrombo-embolic events were rare but associated with high short- and long-term morbidity and mortality, and substantial numbers of patients are not receiving oral anticoagulattherapy before and, despite this risk, after a first thrombolic event.
Abstract: Aims We investigated baseline characteristics, antithrombotic use, and clinical outcomes of patients with atrial fibrillation (AF) and a thrombo-embolic event in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study to better inform the care of these high-risk patients. Method and results Thrombo-embolic events were defined as stroke (ischaemic or unknown cause) or systemic embolism (SE). Clinical outcomes were estimated using the Kaplan-Meier method. All-cause mortality and International Society on Thrombosis and Haemostasis (ISTH) major bleeding after events were analysed using a Cox proportional hazards model with time-dependent covariates. Of 18 201 patients in ARISTOTLE, 365 experienced a thrombo-embolic event [337 strokes (ischaemic or unknown cause), 28 SE]; 46 (12.6%) of which were fatal. In the 30 days before and after a thrombo-embolic event, 11% and 37% of patients, respectively, were not taking an oral anticoagulant. During follow-up (median 1.8 years), 22 patients (7.1%/year) had a recurrent stroke, 97 (30.1%/year) died, and 10 (6.7%/year) had major bleeding. Compared with patients without a thrombo-embolic event, the short- and long-term adjusted hazards of death in patients with a thrombo-embolic event were high [≤30 days: hazard ratio (HR) 54.3%, 95% confidence interval (95% CI) 41.4-71.3; >30 days: HR 3.5, 95% CI 2.5-4.8; both P < 0.001]. The adjusted hazards of major bleeding were also high short-term (HR 10.37, 95% CI 3.87-27.78; P < 0.001) but not long-term (HR 1.7, 95% CI: 0.77-3.88; P = 0.18). Conclusions Thrombo-embolic events were rare but associated with high short- and long-term morbidity and mortality. Substantial numbers of patients are not receiving oral anticoagulattherapy before and, despite this risk, after a first thrombo-embolic event. Clinical Trial Registration ClinicalTrials.gov (NCT00412984).
7 citations