Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease

Abstract

BACKGROUNDThe appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODSUsing an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTSA total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONSIn this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.

Comparison of the Accuracy and Completeness of Records of Serious Vascular Events in Routinely Collected Data vs Clinical Trial–Adjudicated Direct Follow-up Data in the UK

“…Last, because the ASCEND trial was performed in the UK, which has an NHS, it was unable to assess the reliability of routine data in non-UK countries (including those that do not have a single national health care provider) or whether trials were conducted across different countries. However, the ADAPTABLE team of trialists in the US44 have demonstrated the feasibility of a collaborative network (known as the Patient-Centered Clinical Research Network45 ) to perform a large randomized clinical trial of different aspirin doses using electronic health care records as the key method of participant identification and follow-up feasible in a noncentralized health care system.Information From Adjudicated Direct Follow-up for Events Only Considered to Be Serious Vascular Events in Routine Data eTable 7. Information From Routine Data for Events Only Considered to Be Serious Vascular Events in Adjudicated Direct Follow-up eTable 8.…”

A randomised controlled trial to assess the antithrombotic effects of aspirin in type 1 diabetes: role of dosing and glycaemic control

“…Combined with the fact that higher-dose aspirin may hypothetically increase counteractive effects on endothelial prostacyclin release, gastroduodenal integrity and haemostasis, which were not assessed in this study, it seems unlikely that this would translate into a clinical benefit in this patient group [ 30 ]. This is supported by recent data on clinical outcomes from Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE), in which the aspirin regimens 81 mg OD and 325 mg OD were compared in 15,076 patients with established atherosclerotic cardiovascular disease [ 31 ]. After a median of 26 months, there was no significant difference in the rates of a composite primary endpoint of all-cause death, hospitalisation for myocardial infarction or hospitalisation for stroke (7.28% [81 mg] vs. 7.51% [325 mg]; hazard ratio 1.02; 95% confidence interval 0.91 to 1.14; p = 0.75).…”

Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases

“…A loading dose of 250–300 mg is indicated in this context followed by a daily maintenance dose of 75–100 mg as recommended by the European Society of Cardiology (ESC) or 81–325 mg as recommended by the American College of Cardiology [ 28 , 29 , 30 , 31 ]. Remarkably, no significant differences in cardiovascular events or major bleeding was observed in the recently published ADAPTABLE trial between patients with established CVD receiving either 81 mg or 325 mg of aspirin once daily [ 32 ].…”