Comparing PCSK9 Monoclonal Antibody Treatment Strategies Following Myocardial Infarction Using Negative Control Outcomes: A Target Trial Emulation Study.

Background: Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients’ prognostic factors, potentially leading to bias when comparing real-world treatment effects. Methods: Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015–June 2020 for patients aged ≥18 years in Optum’s de-identified Clinformatics Data Mart (CDM) and MarketScan, and those aged ≥66 in the US Medicare claims database. We estimated a 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone–censor–weight approach to address time-varying confounding and immortal person-time. Results: PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = −3.6% [95% CI: −4.3%, −2.9%]), decubitus ulcer (RD = −7.7% [95% CI: −11.8%, −3.7%]), fracture (RD = −8.1% [95% CI: −9.6%, −6.6%]), influenza vaccine (RD = −9.3% [95% CI: −17.5%, −1.1%]), and visual test (RD = −0.6% [95% CI: −0.7%, −0.6%]) under the PCSK9 mAb initiation versus no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies. Conclusion: A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators. [ABSTRACT FROM AUTHOR]