Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

BACKGROUND: The 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. METHODS: Using 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. RESULTS: A 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]). CONCLUSIONS: In 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.).

Validation of Cardiovascular End Points Ascertainment Leveraging Multisource Electronic Health Records Harmonized Into a Common Data Model in the ADAPTABLE Randomized Clinical Trial.

BACKGROUND: The ADAPTABLE trial (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) is the first randomized trial conducted within the National Patient-Centered Clinical Research Network to use the electronic health record data formatted into a common data model as the primary source of end point ascertainment, without confirmation by standard adjudication. The objective of this prespecified study is to assess the validity of nonfatal end points captured from the National Patient-Centered Clinical Research Network, using traditional blinded adjudication as the gold standard. METHODS: A total of 15 076 participants with established atherosclerotic cardiovascular disease were randomized to two doses of aspirin (81 mg and 325 mg once daily). Nonfatal end points (hospitalization for nonfatal myocardial infarction, nonfatal stroke, and major bleeding requiring transfusion of blood products) were captured with the use of programming algorithms applied to National Patient-Centered Clinical Research Network data. A random subset of end points was independently reviewed by a disease-specific expert adjudicator. The positive predictive value of the programming algorithms were calculated separately for end points listed as primary and as nonprimary diagnoses. RESULTS: A total of 225 end points were identified (91 myocardial infarction events, 89 stroke events, and 45 bleeding events), including 142 (63%) that were listed as primary diagnoses. Complete source documents were missing for 14% of events. The positive predictive value were 90%, 72%, and 93% for hospitalizations for myocardial infarction, stroke, and major bleeding, respectively, as compared to adjudication. When only primary diagnoses were considered, positive predictive value were 93%, 91%, and 97%, respectively. When only nonprimary diagnoses were considered, positive predictive value were 82%, 36%, and 71%. CONCLUSIONS: As compared with blinded adjudication, clinical end point ascertainment from queries of the National Patient-Centered Clinical Research Network distributed harmonized data was valid to identify hospitalizations for myocardial infarction in ADAPTABLE. The proportion of contradicted events was high for hospitalizations for bleeding and strokes when nonprimary diagnoses were analyzed, but not when only primary diagnoses were considered.