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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SUBMITTER: Choi H
PROVIDER: S-EPMC10548190 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:The long-term outcome of first-line moderate-intensity statin with ezetimibe combination therapy for secondary prevention after percutaneous coronary intervention in patients with acute coronary syndrome (ACS) compared to high-intensity statin monotherapy remains elusive. The objective of this study was to compare the effectiveness of moderate-intensity statin and ezetimibe combination therapy with high-intensity statin monotherapy. We conducted a nationwide, population-based, retrospective, cohort study of patients with ACS from 2013 to 2019. The patients using combination therapy were matched (1:1) to those using monotherapy. The primary outcome was a composite of myocardial infarction, stroke and all-cause mortality. We estimated the hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards regression. After propensity score matching, 10,723 pairs were selected. Men accounted for 70% of the patients and 37% aged > 70 years. The primary endpoint occurred in 1297 patients (12.1%) in the combination group and in 1426 patients (13.3%) in the monotherapy group, and decreased risk (HR 0.85, 95% CI 0.78-0.92, P < 0.001) in the combination group. Among the patients with ACS, moderate-intensity statin with ezetimibe combination therapy was associated with decreased risk of adverse cardiovascular outcomes compared with high-intensity statin monotherapy in a nationwide population-based study representing routine clinical practice.
| S-EPMC10774297 | biostudies-literature
Project description:Statin is highly recommended for dyslipidemia to prevent atherosclerosis-related cardiovascular diseases and death. The aim of this study was to compare the efficacies and safeties of low/moderate-intensity statin plus ezetimibe combination therapy vs. high-intensity statin monotherapy. Meta-analysis was conducted on data included in published studies performed to compare the effects of the two treatments on lipid parameters and hs-CRP. Safety-related parameters were also evaluated. Eighteen articles were included in the meta-analysis. In terms of efficacy, low/moderate-intensity statin plus ezetimibe reduced LDL-C (SE = 0.307; 95% CI 0.153-0.463), TC (SE = 0.217; 95% CI 0.098-0.337), triglyceride (SE = 0.307; 95% CI 0.153-0.463), and hs-CRP (SE = 0.190; 95% CI 0.018-0.362) significantly more than high-intensity statin therapy. In terms of safety, the two treatments were not significantly different in terms of ALT elevation, but high-intensity statin increased AST and CK significantly more than combination therapy. This analysis indicates that low/moderate-intensity statin plus ezetimibe combined therapy is more effective and safer than high-intensity statin monotherapy, which suggests the addition of ezetimibe to statin should be preferred over increasing statin dose and that high-intensity statin should be used more carefully, especially in patients with related risks.
| S-EPMC8896700 | biostudies-literature
Project description:BackgroundDespite widespread use of high-intensity statin monotherapy, achieving target LDL-C levels and reducing cardiovascular events in patients with or at high risk of developing ASCVD remains challenging. Our study measured the effects of low/moderate-intensity statins and ezetimibe combination therapy compared to high-dose statin monotherapy on major adverse cardiovascular events (MACEs) and coronary atherosclerotic plaque reduction.MethodsWe searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL register of trials for studies comparing the combination therapy to high-intensity statin monotherapy in terms of MACEs and coronary atherosclerotic plaque reduction. The primary outcome was a composite of cardiovascular death or major cardiovascular events (MI, HF, Revascularization, or non-fatal stroke). Other outcomes included other MACEs, lipid-lowering efficacy, and safety outcomes. A protocol was registered to PROSPERO under registration number [CRD42024545807].Results15 studies encompassing 251,450 participants were included in our meta-analysis. In our pooled analysis of observational studies, combination therapy was associated with lower rates of the primary composite outcome (HR = 0.76, CI 95% [0.73, 0.80]), cardiovascular death (HR = 0.80, CI 95% [0.74, 0.88]), all-cause death (HR = 0.84, CI 95% [0.78, 0.91]), and non-fatal stroke (HR = 0.81, CI 95% [0.75, 0.87]). However, the pooled analysis of RCTs did not demonstrate a statistically significant difference between both arms concerning clinical endpoints. Combination therapy had a higher number of patients with LDL-C < 70 mg/dL (RR = 1.27, CI 95% [1.21, 1.34]), significantly lowered LDL-C (MD = -7.95, CI 95% [-10.02, -5.89]) and TC (MD = -26.77, CI 95% [-27.64, -25.89]) in the pooled analysis of RCTs. In terms of safety, the combination therapy lowered muscle-related adverse events (RR = 0.52, CI 95% [0.32, 0.85]) and number of patients with liver enzyme elevation (RR = 0.51, CI 95% [0.29, 0.89]) in the pooled analysis of RCTs and was associated with lower rates of new-onset diabetes (HR = 0.80, CI 95% [0.74, 0.87]) in the pooled analysis of observational studies.ConclusionEvidence from RCTs indicates that low/moderate statin therapy in combination with ezetimibe has a superior lipid-lowering effect and reduces side effects compared to high-dose statins. Observational studies suggest improved clinical outcomes but need to be corroborated by large, outcomes-powered RCTs over longer follow-up periods.
| S-EPMC11577940 | biostudies-literature
Project description:We aimed to evaluate sex differences in the effects of moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg plus ezetimibe) versus high-intensity statin (rosuvastatin 20 mg) monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). This was a sex-specific subgroup analysis of the RACING trial that evaluated the interaction between sex and treatment strategies for the primary outcome (composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years). Of 3780 patients in the RACING trial, 954 (25.2%) were women. Regardless of sex, the effect of moderate-intensity statin with ezetimibe combination therapy on primary outcome compared with high-intensity statin monotherapy was similar (hazard ratio [HR] 0.98 [0.63-1.52] in women; HR 0.90 [0.71-1.14] in men). The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P < 0.001). LDL cholesterol levels of < 70 mg/dL at 1, 2, and 3 years were more frequently achieved in the ezetimibe combination group than in the high-intensity statin monotherapy group (all P < 0.001) in both sexes. There were no significant interactions between sex and treatment groups regarding the primary outcome, discontinuation, or dose reduction of study drugs, or the proportion of achievement of LDL cholesterol levels < 70 mg/dL. The effect of ezetimibe combination therapy for the 3-year composite outcomes was not different in both men and women. The benefits of ezetimibe combination therapy on LDL cholesterol lowering and drug tolerance were similarly observed regardless of sex.Trial registration: https://clinicaltrials.gov ; Unique identifier: NCT03044665.
| S-EPMC10656546 | biostudies-literature
Project description:ImportanceHigh-intensity statin is strongly recommended in patients at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD). However, concerns about statin-associated adverse effects result in underuse of this strategy in practice.ObjectiveTo evaluate the outcomes of a moderate-intensity statin with ezetimibe combination in VHR and non-VHR patients with ASCVD.Design, setting, and participantsThis was a post hoc analysis of the Randomized Comparison of Efficacy and Safety of Lipid Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease (RACING) open-label, multicenter, randomized clinical trial. The study was conducted from February 2017 to December 2018 at 26 centers in Korea. Study participants included patients with documented ASCVD. Data were analyzed from April to June 2022.InterventionsPatients were randomly assigned to moderate-intensity statin with ezetimibe (rosuvastatin, 10 mg, with ezetimibe, 10 mg) or high-intensity statin monotherapy (rosuvastatin, 20 mg). Patients at VHR for ASCVD were defined according to the 2018 American Heart Association/American College of Cardiology guidelines.Main outcomes and measuresThe primary end point was the 3-year outcome of cardiovascular death, coronary or peripheral revascularization, hospitalization of cardiovascular events, or nonfatal stroke.ResultsA total of 3780 patients (mean [SD] age, 64 [10] years; 2826 male [75%]) in the RACING trial, 1511 (40.0%) were categorized as VHR, which was associated with a greater occurrence of the primary end point (hazard ratio [HR], 1.42; 95% CI, 1.15-1.75). There was no significant difference in the primary end point between those who received combination therapy and high-intensity statin monotherapy among patients with VHR disease (11.2% vs 11.7%; HR, 0.96; 95% CI, 0.71-1.30) and non-VHR disease (7.7% vs 8.7%; HR, 0.88; 95% CI, 0.66-1.18). The median low-density lipoprotein cholesterol (LDL-C) level was significantly lower in the combination therapy group than in the high-intensity statin group (VHR, 1 year: 57 [47-71] mg/dL vs 65 [53-78] mg/dL; non-VHR, 1 year: 58 mg/dL vs 68 mg/dL; P < .001). Furthermore, in both the VHR and non-VHR groups, combination therapy was associated with a significantly greater mean change in LDL-C level (VHR, 1 year: -19.1 mg/dL vs -10.1 mg/dL; 2 years: -22.3 mg/dL vs -13.0 mg/dL; 3 years: -18.8 mg/dL vs -9.7 mg/dL; non-VHR, 1 year: -23.7 mg/dL vs -12.5 mg/dL; 2 years: -25.2 mg/dL vs -15.1 mg/dL; 3 years: -23.5 mg/dL vs -12.6 mg/dL; all P < .001) and proportion of patients with LDL-C level less than 70 mg/dL (VHR, 1 year: 73% vs 58%; non-VHR, 1 year: 72% vs 53%; P < .001). Discontinuation or dose reduction of the lipid-lowering drug due to intolerance occurred less frequently in the combination therapy group (VHR, 4.6% vs 7.7%; P = .02; non-VHR, 5.0% vs 8.7%; P = .001).Conclusions and relevanceResults suggest that the outcomes of ezetimibe combination observed in the RACING trial were consistent among patients at VHR of ASCVD.Trial registrationClinicalTrials.gov Identifier: NCT03044665.
| S-EPMC10398545 | biostudies-literature
Project description:PurposeThere are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe combination and whether such regimens have differences in safety. We compared the lipid-modifying efficacy and safety of 5 mg rosuvastatin/10 mg ezetimibe to those of 20 mg rosuvastatin.Materials and methodsA literature search was conducted using the PubMed, EMBASE, Cochrane, Web of Sciences, and SCOPUS databases up to December 2021. Human studies investigating the two aforementioned regimens with a randomized controlled design were selected. Outcome variables included the percentage reduction in LDL-C and other lipid parameters and rates of composite adverse events (AEs), including muscle-related symptoms. A random-effects meta-analysis was performed after heterogeneity testing between studies.ResultsSeven studies were included in this meta-analysis. The percentage LDL-C reduction did not differ between the combination and monotherapy groups [standardized mean difference (SMD) 0.08; 95% confidence interval (CI) -0.09 to 0.26; p=0.35]. The risk of composite AEs (odds ratio 0.50; 95% CI 0.15 to 1.72; p=0.27) of the combination was not different compared to the monotherapy group. The percentage of total cholesterol reduction was greater in the combination group (SMD 0.22; p=0.02), whereas that of triglyceride reduction and high-density lipoprotein cholesterol elevation did not differ between the two groups.ConclusionThis meta-analysis showed that 5 mg rosuvastatin/10 mg ezetimibe had largely comparable lipid-modifying efficacy and tolerability as 20 mg rosuvastatin.
| S-EPMC10774651 | biostudies-literature
Project description:Neither lowering of blood lipid levels nor treatment with statins definitively improves renal outcomes. Ezetimibe, a non-statin antilipidemic agent, is known to not only decrease blood lipid levels but also reduce inflammatory response and activate autophagy. We evaluated the effect of adding ezetimibe to a statin on renal outcome compared with statin monotherapy by analyzing longitudinal data of 4537 patients treated with simvastatin 20 mg plus ezetimibe 10 mg (S + E) or simvastatin 20 mg alone (S) for more than 180 days. A propensity-score-based process was used to match baseline characteristics, medical history, and estimated glomerular filtration rate (eGFR) between S + E and S groups. Changes in serum creatinine and incidence of renal events, defined as doubling of serum creatinine to ≥1.5 mg/dL or occurrence of end-stage renal disease after the first day of treatment initiation, were compared between the groups. Among 3104 well-matched patients with a median follow-up of 4.2 years, the S + E group showed a significantly lower risk of renal events than the S group (hazard ratio 0.58; 95% CI 0.35-0.95, P = 0.032). In addition, the S + E group tended to preserve renal function compared with the S group throughout follow-up, as assessed by serum creatinine changes (P-values for time-group interactions <0.001). These data support the beneficial effects on renal function when combining ezetimibe with a statin.
| S-EPMC7141215 | biostudies-literature
Project description:BackgroundThe objective of this study was to conduct a comparative evaluation of the effectiveness of ezetimibe in combination with statins or statin monotherapy in patients with hypercholesterolemia in a real-world setting.MethodsIt was a retrospective multicenter observational study conducted in Russia. We included patients who received statins or a combination of statins with ezetimibe for ≥3 months. The primary endpoint of this study was the frequency of achieving low-density lipoprotein cholesterol (LDL-C) goal levels at the time of enrollment in the study (%).ResultsThe full analysis set consisted of 1000 patients: 250 subjects in the statin monotherapy group and 750 subjects in the combination group. The groups did not differ in clinical, demographic, or laboratory variables, except for a higher prevalence of hypertension and higher baseline lipid values in the statin monotherapy group. During treatment, the LDL-C concentration decreased by 1.10 ± 1.04 mmol/L (change of -27.5 ± 28.5% from baseline) in the statin monotherapy group and by 1.55 ± 1.17 mmol/L (change of -38.2 ± 25.6% from baseline) in the combination therapy group, p < 0.001. The target LDL-C level was achieved in 22.4% of the patients in the monotherapy group compared with 28.8% of the patients in the combination therapy group, p = 0.049.ConclusionsIn real-world clinical practice, statin/ezetimibe combination therapy demonstrated a more frequent achievement of target LDL-C levels compared with statin monotherapy. The addition of ezetimibe to statin therapy increased the probability of achieving LDL-C level goals by 29%.
| S-EPMC10660455 | biostudies-literature
Project description:Background and objectivesLipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy.MethodsUsing the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.ResultsThe 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.ConclusionsCompared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
| S-EPMC11361771 | biostudies-literature
Project description:IntroductionAlthough several studies have shown that a simplified cardiovascular drug treatment leads to better treatment adherence, limited and conflicting findings have been reported on the separate or single-pill combination of the now recommended association between a statin and ezetimibe. We addressed this issue in a large cohort of patients newly treated with statins to whom ezetimibe was additionally administered, either separately or as a single-pill combination.MethodsA total of 256,012 patients (age 40-80 years) from the Lombardy Region (Italy) newly treated with statins during 2011-2013 were followed until 2018 to identify those to whom ezetimibe was added. The 2881 and 5351 patients who started a two-pill or a single-pill combination, respectively, of statin and ezetimibe were identified and matched for propensity score. Adherence to drug therapy at 1 year was measured as the ratio between the number of days in which the drug was available and the days of follow-up (the proportion of days covered; PDC). Patients who had a PDC > 75% or < 25% were, respectively, defined as highly and poorly adherent to drug therapy. Analysis was extended to the association between adherence and the risk of fatal/non-fatal cardiovascular events.ResultsCompared to those prescribed a two-pill combination, those prescribed a single-pill combination had an 87% (75-99%) greater odds of being highly adherent and a 79% (72-84%) lower odds of being poorly adherent to treatment. These advantages were manifest in all strata of age, sex, and clinical profile. The risk of cardiovascular outcomes decreased by 55% in patients with high adherence compared to those with low adherence.ConclusionPatients who were prescribed a single-pill combination of statin/ezetimibe more frequently exhibit a good adherence and less frequently bad adherence to treatment than those prescribed a two-pill combination of these drugs.
| S-EPMC8478750 | biostudies-literature