Use of Administrative Claims Data to Estimate Treatment Effects for Thirty Versus Twelve Months of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: Findings from the EXTEND-DAPT Study

Using administrative claims data to ascertain clinical events may be a pragmatic way to make randomized controlled trials cheaper and more efficient. However, little is known about accuracy of claims data for estimating treatment effects of randomized therapies.

To evaluate this further, we compared outcomes ascertained using Medicare claims linked with adjudicated outcomes in the Dual Antiplatelet Therapy (DAPT) Study (clinical trial registration number NCT00977938), a randomized trial comparing 30 vs. 12 months of DAPT with aspirin and a P2Y12 inhibitor after percutaneous coronary intervention (PCI).¹ This investigation was part of the Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data (EXTEND) Study,^2,3 and includes DAPT Study data linked to the American College of Cardiology’s (ACC) National Cardiovascular Data Registry (NCDR) CathPCI Registry® and Medicare fee-for-service claims. Analyses were approved by the Institutional Review Board at Beth Israel Deaconess Medical Center with waiver of informed consent.

The DAPT Study enrolled participants between August 13, 2009 and July 1, 2011. At 12 months following PCI, patients without ischemic or bleeding events in the prior year were randomized to placebo (12 months of DAPT) or continued P2Y12 Inhibitor for 18 months (30 months of DAPT). This analysis included all U.S. patients in the DAPT Study who were ≥ 65 years of age and could be linked via the NCDR CathPCI Registry to Medicare claims using deterministic algorithms based on patient identifiers. We compared treatment effects using claims-derived vs. adjudicated events for extended duration DAPT vs. standard duration DAPT on major adverse cardiovascular and cerebrovascular events (MACCE, a composite of death, myocardial infarction [MI], or stroke), MI, and major bleeding. Events in trial data were based on adjudication by the DAPT Study clinical events committee, and claims events were based on International Classification of Diseases, 9^th Revision (ICD-9) diagnosis codes from inpatient Medicare data. Follow-up was from randomization to 18 months post-randomization (12 to 30 months following PCI). Absolute risk differences (ARD) using Kaplan-Meier methods and hazard ratios using Cox regression were compared using claims-derived and adjudicated events, accounting for competing risk of death based on Fine-Gray methods and intra-class correlation using robust covariance estimation.^4,5 Given the post-hoc nature of this analysis, all findings were considered exploratory.

Among 11,648 randomized patients, 1,336 (11.5%) were included in this analysis. Patients outside the U.S. (n = 1756), <65 years old (n = 5984), lacking sufficient identifying information (n = 1880), or with Medicare Advantage (n = 692) were excluded. In the linked cohort, 678 were randomized to 30 months of DAPT and 658 were randomized to 12 months. Cumulative incidence of MACCE and MI for randomized groups were similar using claims-derived and adjudicated events, and both ascertainment methods showed numerically higher bleeding rates in the 30-month group (Figure). ARDs comparing MACCE for 30 vs. 12 months of DAPT were similar: −1.2% (95% confidence interval [CI] −3.8%, +1.4%) with claims and −1.0% (95% CI −3.7%, +1.7%) with adjudication. ARDs for MI (−1.3% [95% CI −3.1%, +0.6%] with claims and −0.6% [95% CI −2.7%, +1.4%] with adjudication) and bleeding (+2.5% [95% CI −0.3%, +5.3%] with claims and +1.9% [95% CI −0.2%, +4.1%] with adjudication) were variable, though not statistically different. In analyses of number needed to treat (NNT) and number needed to harm (NNH) with extended duration DAPT, point estimates using claims-derived vs. adjudicated events were NNT 86 vs. 100 to prevent one MACCE event, NNT 80 vs. 156 to prevent one MI, and NNH 41 vs. 52 to cause one bleeding event, respectively.

Figure. Outcomes for 30 vs. 12 Months of DAPT Using Clinical Trial Adjudication and Medicare Claims.

Cumulative incidence of MACCE (A & B), myocardial infarction (C & D), and major bleeding (E a& F) using adjudicated trial outcomes and Medicare claims from 0 to 18 months following trial randomization in the DAPT Study (12 to 30 months following PCI). DAPT = Dual Antiplatelet Therapy, MACCE = Major Adverse Cardiovascular and Cerebrovascular Events (a composite of mortality, myocardial infarction, or stroke), MI = myocardial infarction.

Relative effects of 30 vs. 12 months of DAPT on MACCE were similar in magnitude and direction whether based on claims or adjudicated events (claims HR 0.82 [95% CI 0.53–1.26] vs. trial HR 0.85 [95% CI 0.56–1.29]; interaction = 0.79). Relative effects for MI (claims HR 0.67 [95% CI 0.36–1.24] vs. trial HR 0.84 [95% CI 0.48–1.47]; interaction p = 0.29) and bleeding (claims HR 1.42 [95% CI 0.95–2.12] vs. trial HR 1.61 [95% CI 0.94–2.75]; interaction p = 0.56) were similar in direction with non-significant differences in magnitude.

This study suggests that treatment effects of extended duration DAPT after PCI using claims-derived events may be similar to those using adjudicated events, with several caveats. We observed some differences that were numerically different but did not reach criteria for statistical significance. Such differences between claims and adjudication could potentially alter conclusions in a larger, adequately powered study. This was also a subgroup of older patients linked to Medicare, and our findings may not apply to other populations. For trials particularly focused on an older U.S.-based population, our data suggest that claims may be cautiously used as a supplement to current adjudication methods or other strategies such as utilization of electronic health records. Further evaluation of claims data in the context of clinical trials is needed.