Abstract
Introduction: To date multiple ongoing clinical trials are testing impact of human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) with established CVD already receiving optimal statin treatment. There is considerable interest in exploring added value of these therapies among high risk groups free of established CVD such as those with diabetes mellitus (DM). Coronary artery calcium (CAC) testing has shown to accurately identify those at high and low risk for cardiac event in short-intermediate term. The aim of the current study is to assess potential implications of enrichment strategies via CAC testing for future clinical trials evaluating impact of PCSK-9 inhibitors in DM free of established CVD
Methods: In our analysis, 5-year CVD rates among DM individuals were estimated from published literature. In the placebo (control) group, 30% relative risk reduction (RRR) with highest tolerated statin dose was considered. The NNT and drug cost with additional PSCK-9 inhibitor therapy to prevent one cardiac event were calculated across varying (20-40%) RRR thresholds. The annual cost of PCSK-9 inhibitors was estimated in range of $3000-$7,000. We considered ≤ $0.5 million as upper limit for willingness to pay to prevent 1 CVD event in 5 years.
Results: The table highlights a) absolute event rates with additional PCSK-9 inhibition, b) the calculated NNT, and c) costs to prevent one cardiac event across the entire DM cohort as well among CAC subgroups. Among all diabetics, the NNT to prevent one event ranged from 48-95 with estimated additional 20-40% RRR with PCSK-9 inhibitors; the threshold for willingness to pay in all scenarios was >$ 0.5 million. The respective NNT among 38% of diabetics with CAC=0 were 89-179 and unacceptable high cost to prevent 1 event. Among individuals with at least moderate CAC burden (>100 & >400), the threshold for willingness to pay was realized in most scenarios
Conclusion: It is imperative that future discussion designing clinical trials assessing efficacy of PCSK-9 inhibitors such as DM focus on enrichment strategies such as CAC testing for recruiting an appropriately ‘high risk’ cohort as well as excluding those who are least likely to benefit. These strategies will likely facilitate acceptable NNT and public willingness to pay for these emerging novel therapies
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