Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are a new class of lipid-lowering therapy (LLT) that offer additional low-density lipoprotein cholesterol (LDL-C) reduction beyond statins and other non-statin LLTs.
Purpose: To explore LLT treatment options required to achieve LDL-C <70 mg/dL in a real-world cohort with atherosclerotic cardiovascular disease (ASCVD).
Methods: Patients with ASCVD were identified in the MarketScan Research database in the US during 2013 and classified as being on high-intensity statin (HIS), moderate-to-low intensity statin (MIS) and/or ezetimibe (EZE). Individual patients were sampled with replacement (bootstrapping) and entered into a simulation model which applied stepwise treatment intensification logic and predicted achievement of LDL-C <70 mg/dL at each step. All patients not initially on a statin were given atorvastatin 20 mg and the following intensification steps were applied: uptitration to atorvastatin 80 mg, add-on EZE, add-on alirocumab 75 mg, uptitration to alirocumab 150 mg. Efficacy was estimated from published studies and incorporated patient-level variation in response to each therapy.
Results: Overall 83,440 patients met the inclusion criteria. Mean age was 66 years; 57% were male; 69%, 38% and 31% respectively had coronary, cerebrovascular and peripheral disease; and 37% had concomitant diabetes. The figure shows the LDL-C distribution before and after treatment intensification. Before treatment intensification 36%, 15%, 2% and 1% respectively were on MIS, HIS, MIS+EZE and HIS+EZE; 26% achieved LDL-C <70 mg/dL. After treatment intensification, 43%, 25%, 1%, 14% and 17% respectively were on MIS, HIS, MIS+EZE, HIS+EZE and HIS+EZE+PCSK9i; 97% achieved LDL-C <70 mg/dL.
Conclusion: Many ASCVD patients not at LDL-C goal are not on maximal oral LLT. Assuming no tolerability issues, opportunities exist for around 62% patients who are not at LDL-C goal to achieve it through intensification of oral therapy only. Overall, approximately 17% ASCVD patients would require maximal multidrug treatment including a PCSK9i to achieve an LDL-C goal <70 mg/dL.