Abstract 471: Impact of Enrichment Strategies for Future Clinical Trials Assessing PCSK-9 Inhibitors Efficacy in Primary Prevention Settings
Introduction: To date multiple ongoing clinical trials are testing impact of human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) in high risk patients with established CVD already on statins. It is of interest to explore the added value of these therapies in individuals free of established CVD. The aim of this study is to assess the implications of population baseline risk considered for clinical trials, in evaluating impact of PCSK9 inhibitors in primary prevention settings.
Methods: We simulated scenarios among primary prevention cohorts recruited with 5 year CVD event rates ranging from 5-25%. In the control group, 30% relative risk reduction (RRR) with highest tolerated statin dose was considered. The NNT and drug cost with additional PSCK9 inhibitor therapy to prevent one cardiac event were calculated across varying (20-40%) RRR thresholds. The annual cost of PCSK9 inhibitors was estimated in range of $3000-$7,000. We considered ≤ $0.5 million as upper limit for willingness to pay to prevent 1 event in 5 years.
Results: The table highlights: a) absolute event rates anticipated in the controls as well with additional PCSK9 inhibition; b) the calculated NNT; and c) costs to prevent one cardiac event across the spectrum of baseline CVD risk levels. Among those with estimated 5 year absolute risk of 10%, the threshold for willingness to pay was achieved provided PCSK9 inhibition achieved 40% RRR with annual cost of $3000. Among individuals with >20% absolute 5 year baseline risk, the threshold for willingness to pay was realized even with 20% RRR in all scenarios if annual cost was limited to $3000.
Conclusion: Future discussion for clinical trials assessing efficacy of PCSK9 inhibitors in reducing CVD events in primary prevention settings must focus on enrichment strategies for recruiting a ‘high risk’ population. These strategies will likely facilitate acceptable NNT and public willingness to pay for these emerging novel therapies.
Author Disclosures: K. Nasir: None. E. Veledar: None.
- © 2015 by American Heart Association, Inc.