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Differential association of ezetimibe-simvastatin combination with major adverse cardiovascular events in patients with or without diabetes: a retrospective propensity score-matched cohort study.

ABSTRACT: Clinical trials suggested that the benefits of ezetimibe-statin combination therapy on major adverse cardiovascular events (MACE) might be greater in patients with diabetes. We aimed to investigate the differential association of ezetimibe-statin combination with incident MACE by presence of diabetes. In this retrospective cohort study, subjects treated with simvastatin 20?mg plus ezetimibe 10?mg (S?+?E) or simvastatin 20?mg alone (S) between 2005 and 2015 were 1:1 matched using propensity score as stratified by diabetes. Primary outcome was newly-developed MACE composed of cardiovascular death, ACS, coronary revascularization, or non-hemorrhagic stroke. During 5,077 and 12,439 person-years, the incidence rates of MACE were 24.9, 20.1, 35.3, and 22.8/1000 person-years among no diabetes S, no diabetes S?+?E, diabetes S, and diabetes S?+?E, respectively. Relative to no diabetes S, adjusted HR (aHR) for MACE in diabetes S was 1.23 (p?=?0.086), whereas S?+?E was associated with a lower risk of MACE in both non-diabetic patients (aHR 0.76, p?=?0.047) and diabetic patients (aHR 0.60, p?=?0.007) with significant difference (relative excess risk due to interaction?=?-0.39, p?=?0.044). In conclusion, reduction of MACE risk associated with ezetimibe plus simvastatin therapy relative to simvastatin alone was greater in patients with diabetes than in patients without diabetes.

SUBMITTER: Lee YH

PROVIDER: S-EPMC6085319 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Differential association of ezetimibe-simvastatin combination with major adverse cardiovascular events in patients with or without diabetes: a retrospective propensity score-matched cohort study.

Lee Yong-Ho YH Hong Namki N Lee Chan Joo CJ Park Sung Ha SH Lee Byung-Wan BW Cha Bong-Soo BS Kang Eun Seok ES

Scientific reports 20180809 1

Clinical trials suggested that the benefits of ezetimibe-statin combination therapy on major adverse cardiovascular events (MACE) might be greater in patients with diabetes. We aimed to investigate the differential association of ezetimibe-statin combination with incident MACE by presence of diabetes. In this retrospective cohort study, subjects treated with simvastatin 20 mg plus ezetimibe 10 mg (S + E) or simvastatin 20 mg alone (S) between 2005 and 2015 were 1:1 matched using propensity score ...[more]

PMID: 30093717

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Project description:Background In randomized trials (SHARP [Study of Heart and Renal Protection], IMPROVE -IT [Improved Reduction of Outcomes: Vytorin Efficacy International Trial]), combination of statin and ezetimibe resulted in additional reduction of cardiovascular events. The reduction was greater in patients with type 2 diabetes mellitus (T2 DM ), where elevated remnant cholesterol and high cardiovascular disease risk is characteristic. To evaluate possible causes behind these results, 40 patients eligible for cholecystectomy, randomized to simvastatin, ezetimibe, combined treatment (simvastatin+ezetimibe), or placebo treatment during 4 weeks before surgery, were studied. Methods and Results Fasting blood samples were taken before treatment start and at the end (just before surgery). Bile samples and liver biopsies were collected during surgery. Hepatic gene expression levels were assessed with qPCR . Lipoprotein, apolipoprotein levels, and content of cholesterol, cholesteryl ester, and triglycerides were measured after lipoprotein fractionation. Lipoprotein subclasses were analyzed by nuclear magnetic resonance. Apolipoprotein affinity for human arterial proteoglycans ( PG ) was measured. Biomarkers of cholesterol biosynthesis and intestinal absorption and bile lipid composition were analyzed using mass spectrometry. Combined treatment caused a statistically significant decrease in plasma remnant particles and apolipoprotein B (ApoB)/lipoprotein content of cholesterol, cholesteryl esters, and triglycerides. All treatments reduced ApoB-lipoprotein PG binding. Simvastatin and combined treatment modified the composition of lipoproteins. Changes in biomarkers of cholesterol synthesis and absorption and bile acid synthesis were as expected. No adverse events were found. Conclusions Combined treatment caused atheroprotective changes on ApoB-lipoproteins, remnant particles, bile components, and in ApoB-lipoprotein affinity for arterial PG . These effects might explain the decrease of cardiovascular events seen in the SHARP and IMPROVE - IT trials. Clinical Trial Registration URL : www.clinicaltrialsregister.eu . Unique identifier: 2006-004839-30).

Project description:BackgroundTreatment guidelines recommend LDL-C as the primary target of therapy in patients with hypercholesterolemia. Moreover, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended when it is not possible to attain LDL-C targets with statin monotherapy. Understanding which treatment or patient-related factors are associated with attaining a target may be clinically relevant.MethodsData were pooled from two multicenter, randomized, double-blind studies. After stabilization on simvastatin 20 mg, patients with coronary heart disease (CHD) alone and/or type 2 diabetes mellitus (T2DM) were randomized to ezetimibe 10 mg/simvastatin 20 mg (EZ/Simva) or simvastatin 40 mg. The change from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, triglycerides, and the proportion of patients achieving LDL-C < 2.6 mmol/L (100 mg/dL) after 6 weeks of treatment were assessed, and factors significantly correlated with the probability of achieving LDL-C < 2.6 mmol/L in a population of high cardiovascular risk Italian patients were identified. A stepwise logistic regression model was conducted with LDL-C < 2.6 mmol/L at endpoint as the dependent variable and study, treatment, gender, age (> or = 65 years or < 65 years), as independent variables and baseline LDL-C (both as continuous and discrete variable).ResultsEZ/Simva treatment (N = 93) resulted in significantly greater reductions in LDL-C, TC, and TC/HDL-C ratio and higher attainment of LDL-C < 2.6 mmol/L vs doubling the simvastatin dose to 40 mg (N = 106). Study [including diabetic patients (OR = 2.9, p = 0.003)], EZ/Simva treatment (OR = 6.1, p < 0.001), and lower baseline LDL-C (OR = 0.9, p = 0.001) were significant positive predictors of LDL-C target achievement. When baseline LDL-C was expressed as a discrete variable, the odds of achieving LDL-C < 2.6 mmol/L was 4.8 in favor of EZ/Simva compared with Simva 40 mg (p < 0.001), regardless of baseline LDL-C level.ConclusionEZ/Simva is an effective therapeutic option for patients who have not achieved recommended LDL-C treatment targets with simvastatin 20 mg monotherapy.Trial registrationClinical trial registration numbers: NCT00423488 and NCT00423579.

Project description:Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy (R(2)Y=0.74; Q(2)=0.66; cross-validated ANOVA P=7.0×10(-8)) and combination therapy (R(2)Y=0.67; Q(2)=0.54; cross-validated ANOVA P=2.6×10(-5)). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks (R(2)Y=0.65; Q(2)=0.61; cross-validated ANOVA P=5.4×10(-8)). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups (q<0.00005), whereas phosphatidylethanolamine (36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease.

Project description:ImportanceAlthough contact isolation has been widely recommended for multidrug-resistant organisms, contact isolation has raised some concerns that it may bring unintended patient harms.ObjectiveTo compare adverse events between a contact isolation group with vancomycin-resistant Enterococcus (VRE) and a matched comparison group using a relatively large data set from full electronic medical records (EMR) and propensity score-matching methods.Design, setting, and participantsThis retrospective, matched cohort study was conducted at Seoul National University Bundang Hospital (SNUBH) in Korea, a tertiary, university-affiliated hospital that has 1337 inpatient beds. Participants included a total of 98 529 hospitalized adult patients (aged ≥18 years) during 2015 to 2017.ExposuresContact isolation in a single or shared double room.Main outcomes and measuresAs adverse contact isolation-related outcomes, falls and pressure ulcers were included. All relevant EMR data were extracted from the SNUBH clinical data warehouse. Risk factors for adverse events were included in the propensity score model based on literature reviews, such as Braden scale score and Hendrich II fall risk score. A fine stratification and weighting (FSW) and a 1:10 nearest neighbor (NN) propensity score matching as a sensitivity analysis were adopted to compare adverse events between the 2 groups for the observation period from the study entry date and the exit date. Time-to-event analyses with a Cox proportional hazard model were conducted in December 2021.ResultsFor comparison of outcomes in wards, 177 patients (mean [SD] age, 67.38 [14.12] years; 98 [55.4%] female) with VRE and 93 022 patients (mean [SD] age, 56.44 [16.88] years; 49 462 [53.2%] female) without VRE were included and no difference was found in basic characteristics from the FSW (VRE contact isolation [n = 172] vs comparison [n = 69 434]) as well as from the 1:10 NN (VRE contact isolation [n = 168] vs comparison [n = 1650]). Among 177 patients with VRE contact isolation, 8 pressure ulcers and 3 falls occurred during their hospital stays; incidence rates of adverse events were 2.5 and 0.9 per 1000 patient-days, respectively (pressure ulcer incidence rate from the FSW: 2.53 per 1000 patient-days [95% CI, 1.09-4.99 per 1000 patient-days]; pressure ulcer incidence rate from the 1:10 NN: 2.54 per 1000 patient-days [95% CI, 1.10-5.01 per 1000 patient-days]; fall incidence rate from the FSW: 0.87 per 1000 patient-days [95% CI, 0.18-2.54 per 1000 patient-days]; fall incidence rate from the 1:10 NN: 0.87 per 1000 patient-days [95% CI, 0.18-2.55 per 1000 patient-days]). The hazard ratios for adverse events showed no statistically significant differences for both groups: 1.42 (95% CI, 0.67-2.99) for pressure ulcer and 0.66 (95% CI, 0.20-2.13) for fall from the FSW.Conclusions and relevanceIn this cohort study, no association was found between the likelihood of adverse events and contact isolation using propensity score-matching methods and closely related covariates for adverse events.

Project description:BackgroundThis study aimed to investigate the association of sodium-glucose cotransporter 2 inhibitors (SGLT2i) use with cardiovascular (CV) clinical outcomes in type 2 diabetes (T2D) patients with acute coronary syndrome (ACS).MethodsData of T2D patients hospitalized for ACS at Civil Aviation General Hospital from January 2019 to December 2022 were collected. Based on SGLT2i use or not, patients were stratified as SGLT2i group and SGLT2i-free group. A 1:1 nearest-neighbor propensity score-matched (PSM) was performed to adjust for the confounding factors and facilitate the robust comparisons between groups. The first occurrence of major adverse cardiovascular events (MACE) with 1 year follow-up, which consisted of CV death, all cause death, non-fatal myocardial infarction or stroke, coronary revascularization or heart failure readmission, was assessed. Kaplan-Meier analysis and Cox regressions were conducted to evaluate the prognostic significance of SGLT2i use. Subgroup analyses were performed to assess the interaction between subgroups and SGLT2i use.ResultsA total of 925 patients were included, and the SGLT2i use increased from 9.9% in 2019 to 43.8% in 2022. 226 pairs were finally matched using the PSM model. During 1 year follow-up period, a total of 110 patients experienced MACE in the matched cohort, with a rate of 24.3%. Survival analyses showed cumulative incidence of MACE, CV death, and heart failure readmission in the SGLT2i group were significantly lower than the SGLT2i-free group. Additionally, the adjusted Cox analyses demonstrated that SGLT2i was associated with a 34.1% lower risk of MACE (HR 0.659, 95% CI 0.487-0.892, P = 0.007), which was primarily driven by a decrease in the risk of CV death by 12.0% (HR 0.880, 95% CI 0.7830.990, P = 0.033), and heart failure readmission by 45.5% (HR 0.545, 95% CI 0.332-0.893, P = 0.016). This MACE preventive benefit was consistent across different subgroups (P interaction > 0.05 for all comparisons).ConclusionsIn T2D patients with ACS, there was a clear increasing trend in SGLT2i use. SGLT2i was associated with a significantly lower risk of MACE, driven by the decrease in the risk of CV death, and heart failure readmission. Our study confirmed real-world use and efficacy of SGLT2i in a general T2D population with ACS.

Project description:BackgroundTyrosine kinase inhibitors (TKIs) have shown long-term survival benefits in patients with chronic myeloid leukemia (CML). Nevertheless, significant concern has been raised regarding long-term TKI-associated vascular adverse events (VAEs). The objective of this retrospective cohort study was to investigate the incidence of VAEs in Taiwanese patients with CML treated with different TKIs (imatinib, nilotinib, and dasatinib) as well as potential risk factors.Materials and methodsWe conducted a retrospective cohort study using the Taiwan Cancer Registry Database and National Health Insurance Research Database. Adult patients diagnosed with CML from 2008 to 2016 were identified and categorized into three groups according to their first-line TKI treatment (imatinib, nilotinib, and dasatinib). Propensity score matching was performed to control for potential confounders. Cox regressions were used to estimate the hazard ratio (HR) of VAEs in different TKI groups.ResultsIn total, 1,111 patients with CML were included in our study. We found that the risk of VAEs in nilotinib users was significantly higher than that in imatinib users, with an HR of 3.13 (95% confidence interval (CI), 1.30-7.51), whereas dasatinib users also showed a nonsignificant trend for developing VAEs, with an HR of 1.71 (95% CI, 0.71-4.26). In multivariable logistic regression analysis, only nilotinib usage, older age, and history of cerebrovascular diseases were identified as significant risk factors. The annual incidence rate of VAEs was highest within the first year after the initiation of TKIs.ConclusionThese findings can support clinicians in making treatment decisions and monitoring VAEs in patients with CML in Taiwan.Implications for practiceThis study found that patients with chronic myeloid leukemia (CML) treated with nilotinib and dasatinib may be exposed to a higher risk of developing vascular adverse events (VAEs) compared with those treated with imatinib. Thus, this study suggests that patients with CML who are older or have a history of cerebrovascular diseases should be under close monitoring of VAEs, particularly within the first year after the initiation of tyrosine kinase inhibitors.

Dataset Information

Differential association of ezetimibe-simvastatin combination with major adverse cardiovascular events in patients with or without diabetes: a retrospective propensity score-matched cohort study.

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Differential association of ezetimibe-simvastatin combination with major adverse cardiovascular events in patients with or without diabetes: a retrospective propensity score-matched cohort study.

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