(259) High-dose vs. standard-dose influenza vaccine and cardiopulmonary hospitalization or mortality: emulating the INVESTED trial using insurance claims data

Publication Number: 592

Background: The INVESTED randomized controlled trial (RCT) did not show benefits of high-dose (HD) vaccine compared with standard-dose (SD) for a primary composite outcome of cardiopulmonary hospitalization or all-cause mortality and its components in patients with history of myocardial infarction or hospitalizations for heart failure (HHF) during three influenza seasons (2016–2019): primary composite outcome (hazard ratio [HR]=1.05; 95% CI=0.96 to 1.15), cardiopulmonary hospitalization (HR=1.05; 0.96 to 1.16), and all-cause mortality (HR=1.01; 0.84 to 1.21).

Objectives: We emulated the design and measurements of the RCT using US Medicare claims data to assess whether the real-world evidence (RWE) study could reach similar conclusions.

Methods: We identified trial-eligible Medicare beneficiaries who received an HD or SD vaccine for the 2016-2019 influenza seasons. Due to limited data availability, these beneficiaries were all aged >65 years with history of HHF. To align eligibility criteria with the RWE study, we re-analyzed the INVESTED trial data restricting to participants >65 and history of HHF. We compared HRs from the RCT and RWE study for the primary composite outcome and its components after 1:1 propensity score (PS)-matching.

Results: In the RWE study of 59,850 PS-matched pairs, the HD group showed similar risk of the primary composite outcome (HR=0.98; 95% CI=0.96 to 1.00) and cardiopulmonary hospitalization (HR=0.99; 0.97 to 1.00), and lower risk of all-cause mortality (HR=0.94; 0.91 to 0.97) compared with SD. These results were similar to the primary RCT results. However, the RWE study results were more closely concordant with the results after re-analysis of the RCT data restricting to participants with more aligned eligibility criteria with the RWE study: primary composite outcome (RCT HR=1.02; 0.89 to 1.17), cardiopulmonary hospitalization (RCT HR=1.02; 0.88 to 1.18), and all-cause mortality (RCT HR=0.92; 0.72 to 1.16).

Conclusions: Although trial-eligible, the RWE study population represented a subset of the RCT population. While similar to the primary RCT results, the RWE study results were closer to the results after re-analysis of the RCT data with aligned eligibility criteria. This study affirms the importance of considering different distributions of baseline patient characteristics when comparing RCT findings vs. RWE.