Real-world LDL-C Reduction in a Nested Cohort of PCSK9 Inhibitor Patients
Feolo, DA, Biskupiak, JE
Objectives: Proprotein Convertase Subtilisin Kexin Type 9 inhibitors (PCSK9i) are human monoclonal antibodies approved for primary and secondary prevention of ASCVD in the following populations: very high ASCVD risk, established ASCVD, HeFH and HoFH patients. Long-term real-world data and high cost has limited the use of PCSK9i. This study determined real world data on LDL-C reduction in a nested cohort, and compared that data with the FDA clinical studies for evolocumab* and alirocumab±. Real-world data from studies like this are essential for clinicians and payers to determine the future role of these agents in prevention of ASCVD.
Study Design: Data was pulled from a regional health insurance database on patients approved for PCSK9i (N=24). Then using an uncontrolled longitudinal study design (before and after treatment) LDL-C data was collected.
Methods: Percent LDL-C change from baseline and 95% confidence intervals were calculated. The last LDL-C value pretreatment was used to calculate baseline, and the first LDL-C representing a significant change was used to calculate mean LDL-C after treatment and percent change under baseline.
Simple descriptive statistics were used to characterize the baseline and demographic characteristics of the cohorts. The LDL-C percentage reduction endpoint was chosen due to the small sample size and limited follow-up time to measure hard endpoints such as ASCVD events. These percent reduction values were then analyzed using a simple t-test to determine the p-value and 95% confidence interval. Percent achieving an LDL-C <70mg/dL was also calculated. These results were then compared to clinical trials which help established the efficacy of Repatha and Praluent.
Results: Cohort mean LDL-C change was -58.9% (95%CI: -69%, -49%). LAPLACE-2 study (Evolocumab*) LDL-C change was -45% (95%CI: -52%, -39%). Study 2 (Alirocumab±) LDL-C change was -46.0% (95% CI: -53%, -39%). Percent achieving LDL-C goal of our cohort was 67%, while the Repatha study reported 93% and the Praluent study 82%. The baseline median LDL-C of our cohort was 162 mg/dL, while baselines for Repatha and Praluent cohorts were 102 mg/dL.
Conclusions: Despite the similar LDL-C reductions between the real-world cohort and the clinical trials data, the percentage reaching recommended LDL-C goals was significantly less in the real-world. This may indicate that factors such cost, intolerance, non-adherence, lifestyle, and not maximizing conventional lipid modifying background therapies is contributing to the smaller percentage of patients meeting goal in the real-world. Future research could look to describe the reasons why patients fail to meet these goals despite PCSK9 inhibitor therapy.