Lipid-Lowering Efficacy of Combination Therapy With Moderate-Intensity Statin and Ezetimibe Versus High-Intensity Statin Monotherapy: A Randomized, Open-Label, Non-Inferiority Trial From Korea
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Objective: This phase IV, multicenter, randomized controlled, open-label, and parallel clinical trial aimed to compare the efficacy and safety of ezetimibe and moderate intensity rosuvastatin combination therapy to that of high intensity rosuvastatin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). Methods: This study enrolled patients with ASCVD and after a four-week screening period, patients were randomly assigned to receive either rosuvastatin and ezetimibe (RE 10/10 group) or high-intensity rosuvastatin (R20 group) only in a 1:1 ratio. The primary outcome was the difference in the percent change in the mean low-density lipoprotein cholesterol (LDL-C) level from baseline to 12 weeks between two groups after treatment. Results: The study found that after 12 and 24 weeks of treatment, the RE10/10 group had a greater reduction in LDL-C level compared to the R20 group (−22.9±2.6% vs. −15.6 ± 2.5% [p=0.041] and −24.2±2.5% vs. −12.9±2.4% [p=0.001] at 12 and 24 weeks, respectively). Moreover, a greater number of patients achieved the target LDL-C level of ≤70 mg/dL after the treatment period in the combination group (74.6% vs. 59.9% [p=0.012] and 76.2% vs. 50.8% [p<0.001] at 12 and 24 weeks, respectively). Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between two groups. Conclusion: Moderate-intensity rosuvastatin and ezetimibe combination therapy had better efficacy in lowering LDL-C levels without increasing adverse effects in patients with ASCVD than high-intensity rosuvastatin monotherapy.
Abstract
Objective: This phase IV, multicenter, randomized controlled, open-label, and parallel clinical trial aimed to compare the efficacy and safety of ezetimibe and moderate intensity rosuvastatin combination therapy to that of high intensity rosuvastatin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). Methods: This study enrolled patients with ASCVD and after a four-week screening period, patients were randomly assigned to receive either rosuvastatin and ezetimibe (RE 10/10 group) or high-intensity rosuvastatin (R20 group) only in a 1:1 ratio. The primary outcome was the difference in the percent change in the mean low-density lipoprotein cholesterol (LDL-C) level from baseline to 12 weeks between two groups after treatment. Results: The study found that after 12 and 24 weeks of treatment, the RE10/10 group had a greater reduction in LDL-C level compared to the R20 group (−22.9±2.6% vs. −15.6 ± 2.5% [p=0.041] and −24.2±2.5% vs. −12.9±2.4% [p=0.001] at 12 and 24 weeks, respectively). Moreover, a greater number of patients achieved the target LDL-C level of ≤70 mg/dL after the treatment period in the combination group (74.6% vs. 59.9% [p=0.012] and 76.2% vs. 50.8% [p<0.001] at 12 and 24 weeks, respectively). Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between two groups. Conclusion: Moderate-intensity rosuvastatin and ezetimibe combination therapy had better efficacy in lowering LDL-C levels without increasing adverse effects in patients with ASCVD than high-intensity rosuvastatin monotherapy.
참고문헌 (35)
- Naghavi M, "Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016 : a systematic analysis for the Global Burden of Disease Study 2016", Lancet, 390, pp.1151~1210 (2017)
- Roth GA, "Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015", J Am Coll Cardiol, 70, pp.1~25 (2017)
- Grundy SM, "2018 AHA", ACC, AAPA, pp.ABC, ACPM[DOI]
- Ference BA, "Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel", Eur Heart J, 38, pp.2459~2472 (2017)
- Mach F, "2019 ESC", EAS Guidelines for the management of dyslipidaemias : lipid modification to reduce cardiovascular risk, 2020, pp.41, 111~188
- Yang YS, "Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea : a retrospective cohort study", Lipids Health Dis, 19, pp.5~ (2020)
- Naci H, "Comparative tolerability and harms of individual statins : a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials", Circ Cardiovasc Qual Outcomes, 6, pp.390~399 (2013)
- Bruckert E, "Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study", Cardiovasc Drugs Ther, 19, pp.403~414 (2005)
- Dormuth CR, "Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases", BMJ, 348, pp.g3244~ (2014)
- Sudhop T, "Inhibition of intestinal cholesterol absorption by ezetimibe in humans", Circulation, 106, pp.1943~1948 (2002)
- Ballantyne CM, "Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia", Am J Cardiol, 93, pp.1487~1494 (2004)
- Cannon CP, "Ezetimibe added to statin therapy after acute coronary syndromes", N Engl J Med, 372, pp.2387~2397 (2015)
- Khan SU, "A Bayesian network meta-analysis of preventive strategies for contrast-induced nephropathy after cardiac catheterization", Cardiovasc Revasc Med, 20, pp.29~37 (2019)
- Koskinas KC, "Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention : a meta-analysis of randomized trials", Eur Heart J, 39, pp.1172~1180 (2018)
- de Cates AN, "Fixed-dose combination therapy for the prevention of cardiovascular disease", Cochrane Database Syst Rev, 4, pp.CD009868~ (2014)
- Stone NJ, "2013 ACC", AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults : a report of the American College of Cardiology, J Am Coll Cardiol, pp.2014, 63(25 Pt B)[DOI]
- Bays HE, "Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia(the ACTE Study)", Am J Cardiol, 108, pp.523~530 (2011)
- Kim KJ, "Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia : MRS-ROZE(Multicenter Randomized Study of ROsuvastatin and eZEtimibe)", Cardiovasc Ther, 34, pp.371~382 (2016)
- Cannon CP, "Intensive versus moderate lipid lowering with statins after acute coronary syndromes", N Engl J Med, 350, pp.1495~1504 (2004)
- LaRosa JC, "Intensive lipid lowering with atorvastatin in patients with stable coronary disease", N Engl J Med, 352, pp.1425~1435 (2005)
- Pedersen TR, "High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction : the IDEAL study : a randomized controlled trial", JAMA, 294, pp.2437~2445 (2005)
- Stroes ES, "Statin-associated muscle symptoms : impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management", Eur Heart J, 36, pp.1012~1022 (2015)
- Cohen DE, "National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists", Am J Cardiol, 97, pp.77C~81C (2006)
- Sattar N, "Statins and risk of incident diabetes : a collaborative meta-analysis of randomised statin trials", Lancet, 375, pp.735~742 (2010)
- Preiss D, "Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy : a meta-analysis", JAMA, 305, pp.2556~2564 (2011)
- Fulcher J, "Efficacy and safety of LDL-lowering therapy among men and women : meta-analysis of individual data from 174, 000 participants in 27 randomised trials", Lancet, 385, pp.1397~1405 (2015)
- Silverman MG, "Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions : a systematic review and meta-analysis", JAMA, 316, pp.1289~1297 (2016)
- Navarese EP, "Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering : a systematic review and meta-analysis", JAMA, 319, pp.1566~1579 (2018)
- Bays HE, "Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia", Am J Cardiol, 112, pp.1885~1895 (2013)
- Wu NQ, "Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers", Lipids Health Dis, 17, pp.265~ (2018)
- Ran D, "A randomized, controlled comparison of different intensive lipid-lowering therapies in Chinese patients with non-ST-elevation acute coronary syndrome(NSTE-ACS) : ezetimibe and rosuvastatin versus high-dose rosuvastatin", Int J Cardiol, 235, pp.49~55 (2017)
- Kim BK, "Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease(RACING) : a randomised, open-label, non-inferiority trial", Lancet, 400, pp.380~390 (2022)
- Hong SJ, "A phase III, multicenter, randomized, double-blind, active comparator clinical trial to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus rosuvastatin monotherapy in patients with hypercholesterolemia : I-ROSETTE(Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia)randomized controlled trial", Clin Ther, 40, pp.226~241 (2018)
- Ballantyne CM, "Efficacy and safety of rosuvastatin 40 mg alone or in combination with ezetimibe in patients at high risk of cardiovascular disease(results from the EXPLORER study)", Am J Cardiol, 99, pp.673~680 (2007)
- Yang YJ, "Combination therapy of rosuvastatin and ezetimibe in patients with high cardiovascular risk", Clin Ther, 39, pp.107~117 (2017)