Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE)
BackgroundLow-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....
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.953040/full |
| _version_ | 1828779146405216256 |
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| author | Isabella Sudano Francois Mach Tiziano Moccetti Thilo Burkard Christian Fahe Alain Delabays Hans Rickli Pierre-Frédéric Keller Jörn Dopheide Jörn Dopheide Sereina Bodenmann Tom Fiolka Georg Ehret David Spirk David Spirk |
| author_facet | Isabella Sudano Francois Mach Tiziano Moccetti Thilo Burkard Christian Fahe Alain Delabays Hans Rickli Pierre-Frédéric Keller Jörn Dopheide Jörn Dopheide Sereina Bodenmann Tom Fiolka Georg Ehret David Spirk David Spirk |
| author_sort | Isabella Sudano |
| collection | DOAJ |
| description | BackgroundLow-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.MethodsIn 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.ResultsOverall, 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.ConclusionsIn 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. |
| first_indexed | 2024-12-11T16:55:59Z |
| format | Article |
| id | doaj.art-a54c1f7dc8ca4c7f84d085636efe7277 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-11T16:55:59Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-a54c1f7dc8ca4c7f84d085636efe72772022-12-22T00:57:58ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-07-01910.3389/fcvm.2022.953040953040Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE)Isabella Sudano0Francois Mach1Tiziano Moccetti2Thilo Burkard3Christian Fahe4Alain Delabays5Hans Rickli6Pierre-Frédéric Keller7Jörn Dopheide8Jörn Dopheide9Sereina Bodenmann10Tom Fiolka11Georg Ehret12David Spirk13David Spirk14Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, SwitzerlandDivision of Cardiology, University Hospitals Geneva, Geneva, SwitzerlandCardiocentro Ticino, Lugano, Ticino, SwitzerlandDepartment of Cardiology, University Hospital Basel, Basel, SwitzerlandPraxis Fahe AG, Muhen, Muhen, SwitzerlandService of Cardiology, Hospital Morges, Morges, SwitzerlandClinic of Cardiology, Cantonal Hospital St. Gallen, St Gallen, SwitzerlandCardiology Center Delemont, Delemont, SwitzerlandClinic of Angiology, Cantonal Hospital Chur, Chur, Switzerland0Faculty of Medicine, University of Bern, Bern, Switzerland1Medical Department, Sanofi, Vernier, Switzerland1Medical Department, Sanofi, Vernier, SwitzerlandDivision of Cardiology, University Hospitals Geneva, Geneva, Switzerland1Medical Department, Sanofi, Vernier, Switzerland2Institute of Pharmacology, University of Bern, Bern, SwitzerlandBackgroundLow-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.MethodsIn 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.ResultsOverall, 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.ConclusionsIn 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.https://www.frontiersin.org/articles/10.3389/fcvm.2022.953040/fullatherosclerotic cardiovascular diseaseheterozygous familial hypercholesterolemiaLDL-C target attainmentPCSK9 inhibitionstatin intolerance |
| spellingShingle | Isabella Sudano Francois Mach Tiziano Moccetti Thilo Burkard Christian Fahe Alain Delabays Hans Rickli Pierre-Frédéric Keller Jörn Dopheide Jörn Dopheide Sereina Bodenmann Tom Fiolka Georg Ehret David Spirk David Spirk Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE) Frontiers in Cardiovascular Medicine atherosclerotic cardiovascular disease heterozygous familial hypercholesterolemia LDL-C target attainment PCSK9 inhibition statin intolerance |
| title | Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE) |
| title_full | Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE) |
| title_fullStr | Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE) |
| title_full_unstemmed | Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE) |
| title_short | Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE) |
| title_sort | optimized treatment of refractory hypercholesterolemia in patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia with alirocumab optimize |
| topic | atherosclerotic cardiovascular disease heterozygous familial hypercholesterolemia LDL-C target attainment PCSK9 inhibition statin intolerance |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.953040/full |
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