Strategies to bridge therapeutic gap in low-density-lipoprotein cholesterol lowering among 90,590 Chinese population with atherosclerotic cardiovascular diseases on stable statin monotherapy

Abstract

Abstract Background Current guideline recommends addition of PCSK9-inhibitor to achieve low-density-lipoprotein cholesterol (LDL-C) lowering by ≥50% to target LDL-C <1.4mmol/L for patients with established atherosclerotic cardiovascular disease (ASCVD) already on maximum tolerated dose of statin and ezetimibe. Purpose We aimed to evaluate the residual distance to target LDL-C (LDL-C lowered by ≥50% and <1.4mmol/L) in ASCVD patients on statin monotherapy and the proportion projected to reach target LDL-C by up-titration to high potency statin, addition of ezetimibe and PCSK9-inhibitor. Methods We retrospectively analyzed 90,590 patients with ASCVD on stable dose of statin monotherapy prior to lipid profile assessment from 43 public hospitals in Hong Kong between Aug 2016 and Jul 2020. Patients were divided into (i) high potency statin (HP-S; rosuvastatin ≥20mg, atorvastatin ≥40mg or simvastatin ≥80mg) and (ii) non-high potency statin (NHP-S; other statin doses) statin users. We calculated the mean percentage LDL-C reduction required to reach the target of LDL-C lowered by ≥50% and <1.4mmol/L. We assumed up-titration from NHP-S to HP-S would further reduce LDL-C by approximately 5–10%; addition of ezetimibe 15–20% and PCSK-9 inhibitor 50–60%. Results Of 90,590 patients (63.2% male, mean age 66.8±11.3), 80.5% had coronary artery, 1.6% had peripheral artery and 21% had cerebrovascular disease; 18.7% were on HP-S and 81.3% on NHP-S. LDL-C lowered by ≥50% and <1.4mmol/L were not achieved in 96.8% (n=71,333/73,655) patients on NHP-S and 93.9% (n=15,896/16,935) patients on HP-S. In these patients, mean LDL-C was 1.8±0.6 and 1.9±0.6mmol/L and mean percentage LDL-C reduction required to reach target LDL-C goal was 40.5±15.4% and 39.3±17.8%, respectively. The proportion of patients who required 5–10%, 10–30%, 30–60% and >60% further reduction to reach target LDL-C were 2.5%, 22.1%, 65.4% and 9%, respectively. Proportion of NHP-S patients projected to reach LDL-C goal by up-titrating to HP-S is 2.2% (n=1,569/71,333). Addition of ezetimibe is projected to achieve LDL-C target in 20.5% (n=17,519/85,660) patients on HP-S who are not at goal. Overall, 78.1% (n=68,141/87,229) of patients on HP-S and ezetimibe were expected to need PCSK-9 inhibitor and is projected to achieve LDL-C target in 98% of cases (n=66,806/68,141). Conclusion Our “real-world” study showed the use of HP-S in ASCVD patients was low and >90% did not reach LDL-C target. High potency statin plus ezetimibe was projected to bridge about one fifth of these patients to target LDL-C. PCSK-9 inhibitor is likely required in significant number of patients despite HP-S plus ezetimibe. Funding Acknowledgement Type of funding sources: None.