Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE)

Isabella Sudano; Francois Mach; Tiziano Moccetti; Thilo Burkard; Christian Fahe; Alain Delabays; Hans Rickli; Pierre-Frédéric Keller; Jörn Dopheide; Sereina Bodenmann; Tom Fiolka; Georg Ehret; David Spirk

doi:10.3389/fcvm.2022.953040

Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE)

Front Cardiovasc Med. 2022 Jul 15:9:953040. doi: 10.3389/fcvm.2022.953040. eCollection 2022.

Authors

Isabella Sudano¹, Francois Mach², Tiziano Moccetti³, Thilo Burkard⁴, Christian Fahe⁵, Alain Delabays⁶, Hans Rickli⁷, Pierre-Frédéric Keller⁸, Jörn Dopheide^{9

10}, Sereina Bodenmann¹¹, Tom Fiolka¹¹, Georg Ehret², David Spirk^{11

12}

Affiliations

¹ Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.
² Division of Cardiology, University Hospitals Geneva, Geneva, Switzerland.
³ Cardiocentro Ticino, Lugano, Ticino, Switzerland.
⁴ Department of Cardiology, University Hospital Basel, Basel, Switzerland.
⁵ Praxis Fahe AG, Muhen, Muhen, Switzerland.
⁶ Service of Cardiology, Hospital Morges, Morges, Switzerland.
⁷ Clinic of Cardiology, Cantonal Hospital St. Gallen, St Gallen, Switzerland.
⁸ Cardiology Center Delemont, Delemont, Switzerland.
⁹ Clinic of Angiology, Cantonal Hospital Chur, Chur, Switzerland.
¹⁰ Faculty of Medicine, University of Bern, Bern, Switzerland.
¹¹ Medical Department, Sanofi, Vernier, Switzerland.
¹² Institute of Pharmacology, University of Bern, Bern, Switzerland.

Abstract

Background: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). In confirmatory trials, proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab substantially lowered LDL-C and reduced cardiovascular morbidity and mortality. However, the routine clinical use of alirocumab in Switzerland has not yet been studied.

Methods: In this prospective nation-wide cohort study, we aimed to investigate the patient profile and routine clinical efficacy and safety of alirocumab in 207 patients with ASCVD or heterozygous familial hypercholesterolemia and increased LDL-C despite maximally tolerated statin therapy. LDL-C was measured at baseline and after 3-months follow-up.

Results: Overall, mean age was 63 ± 11 years, 138 (67%) were men, and 168 (81%) had statin intolerance (SI). Patients with SI had a higher baseline LDL-C (4.3 ± 1.4 vs. 3.3 ± 1.4 mmol/l; p < 0.001) and less frequently ASCVD (71% vs. 95%; p = 0.002). After 3 months of treatment with alirocumab, LDL-C was reduced from 4.1 ± 1.5 to 2.0 ± 1.2 mmol/l (50.5%; p < 0.001). Mean absolute and relative reductions in LDL-C were similar in patients with vs. without SI (2.2 ± 1.2 vs. 1.9 ± 1.3 mmol/l; p = 0.24 and 49.0 vs. 56.6%; p = 0.11, respectively). In total, adverse events were recorded in 25 (12%) patients, with no new safety signals.

Conclusions: In routine clinical practice, alirocumab was predominantly used in patients with SI suggesting that the great majority of patients with insufficient LDL-C control who would be candidates for alirocumab are not receiving this therapeutic option in Switzerland. LDL-C lowering was potent and similar in patients with and without SI, replicating the favorable efficacy-safety profile of alirocumab from randomized trials.

Keywords: LDL-C target attainment; PCSK9 inhibition; atherosclerotic cardiovascular disease; heterozygous familial hypercholesterolemia; statin intolerance.