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Background: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial., Methods: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest., Results: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007)., Conclusions: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL., Trial Registration: ClinicalTrials.gov, Identifier: NCT02579499., (© 2024. The Author(s).)

Background: The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD)., Methods: In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation., Results: Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69)., Conclusions: High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population., Trial Registration: ClinicalTrials.gov, NCT02579499., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: This study evaluated the safety and efficacy of a moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease., Materials and Methods: In this post-hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high-density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke., Results: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high-intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72-1.32; p = .868). Lower rates of intolerance-related drug discontinuation or dose reduction (3.9% vs. 8.0%; p < .001) and lower low-density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p < .001) were observed with ezetimibe combination therapy versus high-intensity statin monotherapy. Furthermore, the rate of new-onset diabetes was 18.5% and 19.1% in each group (p = .822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population., Conclusions: In patients with MetS and atherosclerotic cardiovascular disease, a moderate-intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high-intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low-density lipoprotein cholesterol levels, but there was no apparent between-group difference in new-onset diabetes., (© 2023 John Wiley & Sons Ltd.)

Objective: Current guidelines recommend that patients with peripheral artery disease (PAD) should be treated with antithrombotic agents, renin-angiotensin-system blockers, and statins. However, the clinical impact of guideline-directed medical therapy (GDMT) on long-term mortality in patients with newly diagnosed PAD remains unclear. We aimed to investigate the prevalence of GDMT and evaluate 5-year mortality according to GDMT after PAD diagnosis., Methods: This retrospective cohort study, using nationwide health insurance claims data in Korea, included patients newly diagnosed with PAD between 2006 and 2015. GDMT was defined as the use of all drugs, including antithrombotic agents, renin-angiotensin-system blockers, and statins, within 3 months of PAD diagnosis. The primary endpoint was all-cause mortality., Results: We investigated 19,561 newly diagnosed patients with PAD without proven cardiovascular disease. Among the study population, 4378 patients (22.4%) were categorized in the GDMT and 15,183 (77.6%) in the non-GDMT groups. During the 5-year follow-up, GDMT showed a lower incidence of all-cause mortality than that of non-GDMT (2.8% vs 4.8%; adjusted hazard ratio, 0.329; 95% confidence interval, 0.257-0.421; P < .001). Even in the propensity-matched population, GDMT showed a lower mortality rate than non-GDMT (hazard ratio, 0.283; 95% confidence interval, 0.217-0.370; P < .001). As the number of guideline-recommended drugs increased, the mortality rate decreased proportionately., Conclusions: After PAD diagnosis, GDMT was associated with a lower incidence of mortality regardless of proven cardiovascular disease. This retrospective analysis showed an insufficient prevalence of GDMT among patients with PAD in real-world practice., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Whether the effect of a combination strategy rather than increasing doses of one drug to lower low-density lipoprotein cholesterol (LDL-C) levels is consistent across baseline LDL-C levels remains uncertain., Methods: In the RACING trial, which showed a non-inferiority of moderate-intensity statin with ezetimibe (rosuvastatin 10 mg with ezetimibe 10 mg) to high-intensity statin (rosuvastatin 20 mg) for the primary outcome (3-year composite of cardiovascular death, major cardiovascular event, or stroke), the heterogeneity in treatment effect according to baseline LDL-C levels was assessed for the primary and secondary outcomes (clinical efficacy and safety)., Results: Of 3780 participants, 2817 participants (74.5%) had LDL-C <100 mg/dL, and 963 participants (25.5%) had LDL-C ≥100 mg/dL. The treatment effect of combination therapy versus high-intensity statin monotherapy was similar among the lower LDL-C subset (8.8% vs. 10.2%; hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.67 to 1.08, p = 0.19) and the higher LDL-C subset (10.8% vs. 9.6 %; HR 1.14, 95% CI 0.76 to 1.7, p = 0.53) without a significant interaction (interaction p = 0.22). Of the secondary outcomes, the 1-, 2-, and 3-year achievement of LDL-C <70 mg/dL was greater in the combination therapy group regardless of baseline LDL-C levels., Conclusions: Among ASCVD patients, there was no heterogeneity in the effect of moderate-intensity statin plus ezetimibe combination therapy in the higher and lower baseline LDL-C levels for the 3-year composite of cardiovascular outcomes., Competing Interests: Declaration of competing interest Byeong-Keuk Kim has received speaker's fees from Medtronic and Abbott Vascular, Myeong-Ki Hong has received speaker's fees from Medtronic, Abbott Vascular, and Pfizer, Yangsoo Jang has received institutional research grants from Biotronik and Hanmi, and Jung-Sun Kim has received proctoring fees from Abbott Vascular. All other authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

Objective: To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease., Design: Randomised, open label, multicentre trial., Setting: 12 hospitals in South Korea, September 2016 to November 2019., Participants: 4400 adults (age ≥19 years) with coronary artery disease., Interventions: Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation., Main Outcome Measures: The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities., Results: 4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% v 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% v 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups., Conclusions: In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin., Trial Registration: ClinicalTrials.gov NCT02579499., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: the study was funded by a grant from Sam Jin Pharmaceutical and Chong Kun Dang Pharmaceutical. M-KH has received speaker’s fees from Medtronic, Edward Lifesciences, and Viatris Korea, and institutional research grants from Sam Jin Pharmaceutical and Chong Kun Dang Pharmaceutical; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: High-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., Objective: To evaluate the outcomes of a moderate-intensity statin with ezetimibe combination in VHR and non-VHR patients with ASCVD., Design, Setting, and Participants: This 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., Interventions: Patients 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 Measures: The primary end point was the 3-year outcome of cardiovascular death, coronary or peripheral revascularization, hospitalization of cardiovascular events, or nonfatal stroke., Results: A 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 Relevance: Results suggest that the outcomes of ezetimibe combination observed in the RACING trial were consistent among patients at VHR of ASCVD., Trial Registration: ClinicalTrials.gov Identifier: NCT03044665.

Background: The RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial examined the effects of combination therapy with moderate-intensity statin and ezetimibe in patients with atherosclerotic cardiovascular disease compared with high-intensity statin monotherapy., Objectives: This observational study was conducted to evaluate the impact of 2 treatment strategies used in the RACING trial in clinical practice., Methods: After stabilized inverse probability of treatment weighting, a total of 72,050 patients who were prescribed rosuvastatin after drug-eluting stent implantation were identified from a nationwide cohort database: 10,794 patients with rosuvastatin 10 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 61,256 patients with rosuvastatin 20 mg monotherapy. The primary endpoint was the 3-year composite event of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or nonfatal stroke in accordance with the RACING trial., Results: Combination lipid-lowering therapy was associated with a lower occurrence of the primary endpoint (11.6% vs 15.2% for those with high-intensity statin monotherapy; HR: 0.75; 95% CI: 0.70-0.79; P < 0.001). Compared with high-intensity statin monotherapy, combination lipid-lowering therapy was associated with fewer discontinuations of statin (6.5% vs 7.6%; HR: 0.85; 95% CI: 0.78-0.94: P < 0.001) and a lower occurrence of new-onset diabetes requiring medication (7.7% vs 9.6%; HR: 0.80; 95% CI: 0.72-0.88; P < 0.001)., Conclusions: In clinical practice, combination lipid-lowering therapy with ezetimibe and moderate-intensity statin was associated with favorable clinical outcomes and drug compliance in patients treated with drug-eluting stent implantation. (CONNECT DES Registry; NCT04715594)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Cardiovascular Research Center, Seoul, Korea. The funder had no role in the design and conduct of the study; data collection, management, statistical analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events., Objectives: We evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD)., Methods: In this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke., Results: Among the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159)., Conclusions: Moderate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665)., Competing Interests: Funding Support and Author Disclosures Hanmi Pharmaceutical, Seoul, Korea, has provided funding for this paper. Dr Byeong-Keuk Kim has received speaker fees from Medtronic and Abbott Vascular. Dr Myeong-Ki Hong has received speaker fees from Medtronic, Abbott Vascular, and Pfizer. Dr Yangsoo Jang has received institutional research grants from Biotronik and Hanmi. Dr Jung-Sun Kim has received proctoring fees from Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease., Objective: To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease., Design, Setting, and Participants: A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022)., Interventions: Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg., Main Outcomes and Measures: Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points., Results: Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority)., Conclusions and Relevance: Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy., Trial Registration: ClinicalTrials.gov Identifier: NCT02579499.

Aims: This study evaluated the effect of moderate-intensity statin with ezetimibe combination therapy vs. high-intensity statin monotherapy among patients with diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD)., Methods and Results: This was a pre-specified, stratified subgroup analysis of the DM cohort in the RACING trial. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. Among total patients, 1398 (37.0%) had DM at baseline. The incidence of the primary outcome was 10.0% and 11.3% among patients with DM randomized to ezetimibe combination therapy vs. high-intensity statin monotherapy (hazard ratio: 0.89; 95% confidence interval: 0.64-1.22; P = 0.460). Intolerance-related discontinuation or dose reduction of the study drug was observed in 5.2% and 8.7% of patients in each group, respectively (P = 0.014). LDL cholesterol levels <70 mg/dL at 1, 2, and 3 years were observed in 81.0%, 83.1%, and 79.9% of patients in the ezetimibe combination therapy group, and 64.1%, 70.2%, and 66.8% of patients in the high-intensity statin monotherapy group (all P < 0.001). In the total population, no significant interactions were found between DM status and therapy regarding primary outcome, intolerance-related discontinuation or dose reduction, and the proportion of patients with LDL cholesterol levels <70 mg/dL., Conclusion: Ezetimibe combination therapy effects observed in the RACING trial population are preserved among patients with DM. This study supports moderate-intensity statin with ezetimibe combination therapy as a suitable alternative to high-intensity statins if the latter cannot be tolerated, or further reduction in LDL cholesterol is required among patients with DM and ASCVD., Clinical Trial Registration: ClinicalTrials.gov, Identifier:NCT03044665., Competing Interests: Conflict of interest: S.C.Y. is a chief technical officer of PHI Digital Healthcare and has received consulting fee from IQVIA; B.-K.K. has received speaker’s fees from Medtronic and Abbott Vascular; M.-K.H. has received speaker’s fees from Medtronic, Abbott Vascular, and Pfizer, Y.J. has received institutional research grants from Biotronik and Hanmi, and J.-S.K. has received proctoring fees from Abbott Vascular. All other authors declare no competing interests., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed., Methods: In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete., Findings: Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001)., Interpretation: Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction., Funding: Hanmi Pharmaceutical., Competing Interests: Declaration of interests M-KH has received speaker's fees from Medtronic, Abbott Vascular, and Pfizer. YJ has received institutional research grants from Biotronik and Hanmi. B-KK has received speaker's fees from Medtronic and Abbott Vascular. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The efficacy of fixed-dose combinations (FDCs) in improving adherence and risk factor control for cardiovascular disease has not been reported consistently. Here, we compared adherence and efficacy between an olmesartan/rosuvastatin FDC and the usual regimen., Methods: In this 6-month, open-label, randomized, active-control study, we screened 154 patients; of these, 150 were randomly assigned to receive either olmesartan/rosuvastatin FDC or the usual regimen with separate angiotensin receptor blockers and statins. In total, 135 patients completed the study (median age: 68 years; male: 68.9%). The primary outcome was patients' adherence; the secondary outcomes were changes in blood pressure (BP) and lipid parameters., Results: During follow-up, adherence in both groups was high and similar between the groups (98.9% and 98.3% in the FDC and usual regimen groups, respectively, p = 0.328). Changes in systolic (-8 and -5 mmHg, respectively, p = 0.084) and diastolic BP (-5 and -2 mmHg, p = 0.092) did not differ significantly, although they were numerically greater in the FDC group. Changes in low-density lipoprotein cholesterol (LDL-C) were greater in the FDC group (-13 and -4 mg/dL, respectively, p = 0.019), whereas changes in other lipid parameters were similar between the groups. The test drugs were well tolerated, showing no difference in safety between the groups., Conclusions: Patients' adherence was excellent and similar in the groups, whereas the reduction in the LDL-C level was greater in the FDC group. We provide comprehensive information on the adherence and efficacy of an FDC compared to the usual regimen in Korean patients with high cardiovascular risk.

Background: The beneficial effects of statin and renin-angiotensin system inhibitor (RASI) are well-known. In this retrospective cohort study, 2-year clinical outcomes were compared between monotherapy and combination therapy with statin and RASI in ST-segment elevation myocardial infarction (STEMI) patients after stent implantation., Methods: A total of 17,414 STEMI patients were enrolled and divided into the three groups (group A: 2448 patients, statin alone; group B: 2431 patients, RASI alone; and group C: 12,535 patients, both statin and RASI). The principal clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction, and any repeat revascularization., Results: After adjustment, the cumulative incidences of MACEs in group A (adjusted hazard ratio [aHR] 1.337; 95% confidence interval [CI] 1.064-1.679; p = 0.013) and in group B (aHR 1.375; 95% CI 1.149-1.646; p = 0.001) were significantly higher than in group C. The cumulative incidence of all-cause death in group A was significantly higher than that in group C (aHR 1.539; 95% CI 1.014-2.336; p = 0.043). The cumulative incidences of any repeat revascularization (aHR 1.317; 95% CI 1.031-1.681; p = 0.028), target lesion vascularization, and target vessel vascularization in group B were significantly higher than in group C., Conclusions: A statin and RASI combination therapy significantly reduced the cumulative incidence of MACEs compared with a monotherapy of these drugs. Moreover, the combination therapy showed a reduced all-cause death rate compared with statin monotherapy, and a decreased repeat revascularization rate compared with RASI monotherapy.

Background: Limited data are available comparing the combined effects of statins and renin-angiotensin system inhibitor (RASI) between patients with ST-segment elevation myocardial infarction (STEMI) and those with non-STEMI (NSTEMI). We compared the effects of statins combined with RASI in STEMI and NSTEMI patients after stent implantation during a long-term follow-up period., Methods: A total of 21,890 acute myocardial infarction (AMI) patients who underwent successful stent implantation and who received statins with RASI were enrolled. They were separated into the STEMI group (n = 12,490) and the NSTEMI group (n = 9400). The major clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization., Results: Two propensity score-matched (PSM) groups (5891 pairs, n = 11782, C-statistic = 0.821) were generated. Even though the cumulative incidences of MACE, re-MI, total repeat revascularization were similar between the two groups, the cumulative incidences of all-cause death (hazard ratio [HR] 1.407; 95% confidence interval [CI] 1.106-1.790; p = 0.005) and cardiac death (HR 1.311; 95% CI 1.983-1.749; p = 0.046) were significantly higher in the NSTEMI group., Conclusions: In this study, statin with RASI combination therapy was more beneficial to the STEMI patients than to the NSTEMI patients in reducing all-cause death and cardiac death.

Background: Comparative studies regarding the long-term clinical outcomes of statin intensity between acute myocardial infarction (AMI) patients with prediabetes and those with type 2 diabetes mellitus (T2DM), after successful implantation of newer-generation drug-eluting stents (DES) with statin treatment, are limited. We compared the 2-year clinical outcomes between these patients., Methods: A total of 11,612 AMI patients were classified as statin users (n = 9893) and non-users (n = 1719). Thereafter, statin users were further divided into high-intensity (n = 2984) or low-moderate-intensity statin (n = 6909) treatment groups. Those in these two groups were further classified into patients with normoglycemia, prediabetes, and T2DM. The major outcomes were the occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat coronary revascularization., Results: After adjusting for both high-intensity and low-moderate-intensity statin users, the cumulative incidences of MACE (p = 0.737, p = 0.062, respectively), all-cause death, Re-MI, and any repeat revascularization were similar between the prediabetes and T2DM groups. In the total study population, both high-intensity and low-moderate-intensity statin treatments showed comparable results. However, in the patients who enrolled after October 2012, the cumulative incidences of MACE (aHR 1.533; 95% CI 1.144-2.053; p = 0.004) and any repeat revascularization (aHR, 1.587; 95% CI 1.026-2.456; p = 0.038) were significantly lower in high-intensity statin users than in low-moderate intensity statin users. The beneficial effects of high-intensity compared to low-moderate-intensity statin therapy were more apparent in the normoglycemia group than hyperglycemia group, as it reduced the cumulative incidences of MACE (aHR 1.903; 95% CI 1.203-3.010; p = 0.006) and any repeat revascularization (aHR 3.248; 95% CI 1.539-6.854; p = 0.002)., Conclusions: In this retrospective registry study, prediabetes and T2DM groups showed comparable clinical outcomes, after administering both high-intensity and low-moderate-intensity statin treatments. However, these results are likely to be clearly proved by further studies, especially in patients with AMI who are being treated in contemporary practice., Trial Registration: Retrospectively registered., (© 2021. The Author(s).)

Abstract: Studies comparing long-term clinical outcomes of statin treatment between acute myocardial infarction (AMI) patients with prediabetes and those with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) with the newer-generation drug-eluting stents (DESs) are limited. We compared 2-year clinical outcomes between these patients.A total of 11,962 AMI patients were classified as statin users (n = 10,243) and statin nonusers (n = 1719). Thereafter, statin users and nonusers were further divided into the normoglycemia, prediabetes, and T2DM groups. The major outcome was the occurrence of major adverse cardiac event (MACE) defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat coronary revascularization.After statin treatment, the cumulative incidences of MACE (P = .314), all-cause death, cardiac death (CD), Re-MI, and any repeat revascularization were similar between the prediabetes and T2DM groups. However, the cumulative incidences of MACE (P = .025) and all-cause death (P = .038) in the prediabetes group and those of MACE (P = .001), all-cause death (P = .009), and CD (P = .048) in the T2DM group were significantly higher than those in the normoglycemia group. Moreover, in all the 3 glycemic groups, the cumulative incidences of MACE, all-cause death, and CD were significantly higher among statin nonusers than among statin users.This study revealed that AMI patients with prediabetes had worse clinical outcomes than those with normoglycemia and comparable to those with T2DM after 2-year statin treatment. However, further studies are warranted to confirm the current findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Limited data are available on the relapse of statin intolerance after resumption of statins. We aimed to evaluate the relapse rates of statin intolerance in patients who subsequently received pravastatin or fluvastatin and to identify associated factors., Methods: This retrospective, propensity score-matched cohort study screened data obtained from a tertiary university hospital between 2006 and 2015. Of 8073 patients screened, 488 with statin intolerance who received pravastatin or fluvastatin with regular follow-up were enrolled. After propensity score matching of patients, 384 were finally analyzed. The primary outcome variables were relapse of statin intolerance and stopping (ie, discontinuation or switching to other statins) rate for the 2 statins., Results: During the median follow-up period of 37 months, the rate of relapse of intolerance was 10.4% and 18.2% among users of pravastatin and fluvastatin, respectively (P = 0.04). However, the log-rank test showed no difference in the relapse-free rates between the 2 groups (P = 0.34). The stopping rates of the 2 statins were 36.5% and 42.2% (P = 0.30), respectively, for various reasons, including low efficacy of the drugs. After adjustment, chronic kidney disease (hazard ratio [HR] 1.83, P = 0.03) and previous creatine kinase elevation (HR 3.13, P = 0.001) were identified as independent determinants of relapse. Older age (HR 1.03, P = 0.057) and female sex (HR 1.70, P = 0.059) were associated, but not significantly, with relapse., Conclusion: Although a small proportion of patients taking pravastatin or fluvastatin experienced a relapse of intolerance, many patients eventually discontinued or changed these agents. Chronic kidney disease and history of creatine kinase elevation were independent determinants of relapse., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: Studies of the comparative clinical outcomes between statin with angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in ST-segment elevation myocardial infarction (STEMI) patients are limited. We compared 2-year clinical outcomes between statin with ACEI or ARB therapy in STEMI patients after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES)., Methods: A total of 11,706 STEMI patients were enrolled and separated into two groups: the ACEI group (statin + ACEI, n = 8705) and the ARB group (statin + ARB, n = 3001). The primary endpoint was major adverse cardiac events (MACE) defined as all-cause death, recurrent MI (re-MI), and any coronary revascularization. Secondary endpoints were the individual components of MACE and target vessel failure (TVF)., Results: After propensity score-matched (PSM) analysis, two PSM groups (2729 pairs, n = 5458, C-statistic = 0.675) were generated. The cumulative incidences of MACE, re-MI, and any coronary revascularization were similar between the two groups. However, the cumulative incidences of all-cause death (hazard ratio [HR], 1.548; 95% confidence interval [CI], 1.091-2.197; p = 0.014) and cardiac death (HR, 1.850; 95% CI, 1.218-2.811; p = 0.004) were significantly higher in the ARB group compared with the ACEI group after PSM analysis., Conclusions: The combination of statin with ACEI may be the preferred treatment strategy to reduce mortality rates in STEMI patients after successful PCI with DES rather than statin with ARB in this study during a 2-year follow-up period., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction and Objectives: Current guidelines on the treatment of blood cholesterol recommend continuous maintenance of high-intensity statin treatment in drug-eluting stent (DES)-treated patients. However, high-intensity statin treatment is frequently underused in clinical practice after stabilization of DES-treated patients. Currently, the impact of continuous high-intensity statin treatment on the incidence of late adverse events in these patients is unknown. We investigated whether high-intensity statin treatment reduces late adverse events in clinically stable patients on aspirin monotherapy 12 months after DES implantation., Methods: Clinically stable patients who underwent DES implantation 12 months previously and received aspirin monotherapy were randomly assigned to receive either high-intensity (40mg atorvastatin, n = 1000) or low-intensity (20mg pravastatin, n = 1000) statin treatment. The primary endpoint was adverse clinical events at 12-month follow-up (a composite of all death, myocardial infarction, revascularization, stent thrombosis, stroke, renal deterioration, intervention for peripheral artery disease, and admission for cardiac events)., Results: The primary endpoint at 12-month follow-up occurred in 25 patients (2.5%) receiving high-intensity statin treatment and in 40 patients (4.1%) receiving low-intensity statin treatment (HR, 0.58; 95%CI, 0.36-0.92; P = .018). This difference was mainly driven by a lower rate of cardiac death (0 vs 0.4%, P = .025) and nontarget vessel myocardial infarction (0.1 vs 0.7%, P = .033) in the high-intensity statin treatment group., Conclusions: Among clinically stable DES-treated patients on aspirin monotherapy, high-intensity statin treatment significantly reduced late adverse events compared with low-intensity statin treatment., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01557075., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To compare the effects of atorvastatin 10 mg versus 40 mg in circulating angiogenic cell mobilisations and in restoring coronary flow reserve (CFR) during the 8-month follow-up in patients with a first acute myocardial infarction (AMI)., Design: CFR was measured using an intracoronary Doppler wire in 102 patients with AMI at baseline and at 8 months. Changes in the absolute number of circulating angiogenic cells were measured at baseline, 1 day, 5 days and at 8 months. Stented patients were randomly assigned to either low-dose atorvastatin 10 mg (ATOR10, n=52) or moderate-dose atorvastatin 40 mg (ATOR40, n=50). Setting University Hospital., Results: CFR increased significantly in both groups during the 8-month follow-up. The 8-month increases from baseline in CFR were significantly greater in the ATOR40 group than in the ATOR10 group (0.99+/-0.69 vs 0.55+/-0.47, p=0.017, respectively). The serial increases in the absolute number of CD34+ and CXCR4+ cells were significantly greater in the ATOR40 group, especially at 24 h after the procedure (two-way repeated-measures analysis of variance: p=0.046 and p=0.022, respectively). Decreases from baseline for interleukin 6 (-2.94+/-3.31 vs -1.52+/-2.82 pg/ml), tumour necrosis factor alpha (-1.31+/-2.96 vs -0.01+/-1.29 pg/ml), soluble intercellular adhesion molecule-1 (-71+/-95 vs 37+/-83 ng/ml) and soluble vascular cell adhesion molecule-1 (-51+/-364 vs 190+/-204 ng/ml) were significantly greater in the ATOR40 group., Conclusions: The recovery of microvascular integrity after acute ischaemic injury in the ATOR40 group was expedited by greater circulating angiogenic cell mobilisations such as CD34+ and CXCR4+ cells, together with greater decreases in inflammatory cytokines and low-density lipoprotein-cholesterol concentrations. Registration number http://ClinicalTrials.gov number, NCT00536887.