Dirk Jacobus Blom1, Naresh Ranjith2, Pankaj Joshi3, Poobalan Naidoo4, Alet van Tonder5, Moji Ganiyat Musa5, Shaifali Joshi3, Rory Leisegang6, Julien Shane Trokis7, Hemant Makan8, Frederick Johan Raal9. 1. Division of Lipidology and Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Cape Town, South Africa. Email: dirk.blom@uct.ac.za. 2. Cardiovascular Research Centre, Durban, South Africa. 3. Diabetes Care and Clinical Trials Centre, Pretoria, South Africa. 4. Medical Affairs, Sanofi, Midrand, South Africa; Department of Health Informatics, School of Health Professions, Rutgers, State University of New Jersey, NJ, USA. 5. Medical Affairs, Sanofi, Midrand, South Africa. 6. Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden; Family Clinical Research Unit (FAM-CRU), University of Stellenbosch, Tygerberg Hospital, Tygerberg, South Africa. 7. Diabetes Research and Clinical Care, Kraaifontein, Cape Town, South Africa. 8. Centre for Diabetes, Lenasia, South Africa. 9. Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Abstract
BACKGROUND: Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. At the time the study was conducted, guidelines recommended a low-density lipoprotein cholesterol (LDL-C) target of less than 1.8 mmol/l and a reduction of at least 50% if the baseline LDL-C was between 1.8 and 3.5 mmol/l in patients with either very high cardiovascular risk or established atherosclerosis. In South Africa, there is a paucity of data on attainment of LDL-C goal in patients with very high cardiovascular risk who are on maximum tolerated statin with or without ezetimibe. OBJECTIVE: The aim was to assess the percentage of very high cardiovascular risk South African patients with dyslipidaemia not reaching an LDL-C goal of less than 1.8 mmol/l, despite maximum tolerated statin with or without ezetimibe. METHODS: This was a multi-centre, observational, cross-sectional study conducted at 15 private healthcare sector sites and one public sector site. Adults (> 18 years) with very high cardiovascular risk of familial hypercholesterolaemia receiving stable, maximum-tolerated statin therapy for at least four weeks prior to their latest lipid profile were enrolled into the study, and electronic case report forms were completed after written informed consent was provided. LDL-C goal attainment was modelled, first assuming an increase in the statin dose to the registered maximum, followed by the addition of ezetimibe or a PCSK9-inhibitor. RESULTS: In total, 507 patients were screened, of whom 492 were eligible for study participation. One patient was excluded from the analysis because of a missing LDL-C value. Most participants were male (male 329, 67%; female 162, 33%). Most patients were either obese (223, 46.0%) or overweight (176, 36.3%). Hypertension and diabetes mellitus were frequent co-morbidities and were found in 381 (77.6%) and 316 (64.4%) patients, respectively. Eighty (16.3%) patients reported current smoking. Only 68 (13.8%) patients were taking ezetimibe in addition to a statin. Reasons for not using ezetimibe included no requirement for ezetimibe in the opinion of the treating physician (229, 48.7%), cost (149, 31.7%), Physician's choice (39, 8.3%), or other (53, 11.3%). Only 161 (32.8%) of the patients attained their goal LDL-C level. In our modelling analysis, increasing the statin dose to the registered maximum and adding ezetimibe brought an additional 34.5% of patients to goal, while adding a PCSK9-inhibitor, irrespective of any other changes to lipid-lowering therapy brought over 90% of not-at-goal patients to goal. CONCLUSIONS: Most study participants were not at LDL-C goal despite maximum-tolerated statin, highlighting the need for treatment intensification in this high-risk population. Although intensifying treatment by adding a PCSK9-inhibitor brought more patients to goal, the initial addition of ezetimibe would be more reasonable, given the cost of PCSK9-inhibitors.
BACKGROUND: Dyslipidaemia is a major modifiable risk factor for atherosclerotic cardiovascular disease. At the time the study was conducted, guidelines recommended a low-density lipoprotein cholesterol (LDL-C) target of less than 1.8 mmol/l and a reduction of at least 50% if the baseline LDL-C was between 1.8 and 3.5 mmol/l in patients with either very high cardiovascular risk or established atherosclerosis. In South Africa, there is a paucity of data on attainment of LDL-C goal in patients with very high cardiovascular risk who are on maximum tolerated statin with or without ezetimibe. OBJECTIVE: The aim was to assess the percentage of very high cardiovascular risk South African patients with dyslipidaemia not reaching an LDL-C goal of less than 1.8 mmol/l, despite maximum tolerated statin with or without ezetimibe. METHODS: This was a multi-centre, observational, cross-sectional study conducted at 15 private healthcare sector sites and one public sector site. Adults (> 18 years) with very high cardiovascular risk of familial hypercholesterolaemia receiving stable, maximum-tolerated statin therapy for at least four weeks prior to their latest lipid profile were enrolled into the study, and electronic case report forms were completed after written informed consent was provided. LDL-C goal attainment was modelled, first assuming an increase in the statin dose to the registered maximum, followed by the addition of ezetimibe or a PCSK9-inhibitor. RESULTS: In total, 507 patients were screened, of whom 492 were eligible for study participation. One patient was excluded from the analysis because of a missing LDL-C value. Most participants were male (male 329, 67%; female 162, 33%). Most patients were either obese (223, 46.0%) or overweight (176, 36.3%). Hypertension and diabetes mellitus were frequent co-morbidities and were found in 381 (77.6%) and 316 (64.4%) patients, respectively. Eighty (16.3%) patients reported current smoking. Only 68 (13.8%) patients were taking ezetimibe in addition to a statin. Reasons for not using ezetimibe included no requirement for ezetimibe in the opinion of the treating physician (229, 48.7%), cost (149, 31.7%), Physician's choice (39, 8.3%), or other (53, 11.3%). Only 161 (32.8%) of the patients attained their goal LDL-C level. In our modelling analysis, increasing the statin dose to the registered maximum and adding ezetimibe brought an additional 34.5% of patients to goal, while adding a PCSK9-inhibitor, irrespective of any other changes to lipid-lowering therapy brought over 90% of not-at-goal patients to goal. CONCLUSIONS: Most study participants were not at LDL-C goal despite maximum-tolerated statin, highlighting the need for treatment intensification in this high-risk population. Although intensifying treatment by adding a PCSK9-inhibitor brought more patients to goal, the initial addition of ezetimibe would be more reasonable, given the cost of PCSK9-inhibitors.
Authors: Marc S Sabatine; Robert P Giugliano; Anthony C Keech; Narimon Honarpour; Stephen D Wiviott; Sabina A Murphy; Julia F Kuder; Huei Wang; Thomas Liu; Scott M Wasserman; Peter S Sever; Terje R Pedersen Journal: N Engl J Med Date: 2017-03-17 Impact factor: 91.245
Authors: Salim Yusuf; Steven Hawken; Stephanie Ounpuu; Tony Dans; Alvaro Avezum; Fernando Lanas; Matthew McQueen; Andrzej Budaj; Prem Pais; John Varigos; Liu Lisheng Journal: Lancet Date: 2004 Sep 11-17 Impact factor: 79.321
Authors: F Raal; C Schamroth; D Blom; J Marx; M Rajput; M Haus; R Hussain; F Cassim; M Nortjé; G Vandehoven; A-M Temmerman Journal: Cardiovasc J Afr Date: 2011-09-15 Impact factor: 1.167