Dataset Information

Time-Dependent Cardiovascular Treatment Benefit Model for Lipid-Lowering Therapies.

ABSTRACT: Background With the availability of new lipid-lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time-dependent model from published randomized controlled trials summarizing the relationship between low-density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. Methods and Results A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low-density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time-dependent model had better predictions than cholesterol treatment trialists' estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ?2% with intensive treatment with high-intensity statin, ezetimibe, and high-dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high- or moderate-intensity statin alone were achieved in higher-risk populations with 2 to 5 years of treatment, and lower-risk populations with 9 to 11 years of treatment. Conclusions The time-dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid-lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid-lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.

SUBMITTER: Khan I

PROVIDER: S-EPMC7792260 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Time-Dependent Cardiovascular Treatment Benefit Model for Lipid-Lowering Therapies.

Khan Irfan I Peterson Eric D ED Cannon Christopher P CP Sedita Lauren E LE Edelberg Jay M JM Ray Kausik K KK

Journal of the American Heart Association 20200728 15

Background With the availability of new lipid-lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time-dependent model from published randomized controlled trials summarizing the relationship between low-density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios ...[more]

PMID: 32720582

Similar Datasets

Project description:BackgroundHyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs.MethodsWe searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model.ResultsSeven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR?=?1.72, 95% CI 1.28-2.33) and CVE (RR?=?1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR?=?0.35, 95% CI 0.20-0.62) and CVE (RR?=?0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR?=?0.69, 95% CI 0.54-0.88) rather than MACE (RR?=?0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE.ConclusionsThe hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

Project description:The management of low-density lipoprotein cholesterol (LDL-C) levels is a central strategy for the prevention of atherosclerotic cardiovascular disease. Current United States (2018 American Heart Association/American College of Cardiology/Multisociety) and European (2019 European Society of Cardiology/European Atherosclerosis Society) guidelines endorse statin therapy as the first-line therapy for pharmacologic LDL-C lowering. However, in clinical practice up to 30% of patients report partial or complete intolerance to statin therapy. While the nocebo effect with statins is well described, perceived statin intolerance prevents many patients from achieving LDL-C thresholds associated with clinical benefit. Bempedoic acid is a novel, oral, non-statin lipid-l owering therapy that works by inhibiting adenosine triphosphate-citrate lyase, an enzymatic reaction upstream of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the hepatic cholesterol synthesis pathway. Bempedoic acid confers reduction in LDL-C of ~18% on background statin therapy,~21% in patients with statin intolerance, and ~38% when given in fixed-dose combination with ezetimibe. The CLEAR Outcomes trial, which enrolled high-risk primary and secondary prevention patients with reported statin intolerance and LDL-C levels ≥100 mg/dL, showed that bempedoic acid compared with placebo reduced 4-component major adverse cardiovascular events (MACE) by 13% (hazard ratio 0.87, 95% confidence interval 0.79-0.96). Bempedoic acid also reduced 3-component MACE by 15%, myocardial infarction by 23% and coronary revascularization by 19%. The benefit was even greater in the primary prevention cohort (hazard ratio 0.70, 95% confidence interval 0.55-0.89) for 4-component MACE. Bempedoic acid was associated with increases in uric acid levels and cholelithiasis, but numerically fewer events of myalgia and new-onset diabetes. These findings confirm that bempedoic acid is an effective approach to reduce cardiovascular outcomes in high-risk patients with statin intolerance who require further reduction in LDL-C.

Project description:ImportanceGuidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low.ObjectiveTo track LDL-C treatment patterns in the US over 2 years.Design, setting, and participantsGOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020.Main outcomes and measuresThe primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years.ResultsA total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels ≥100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P < .001) and achievement of LDL-C less than 70 mg/dL (teaching vs nonteaching hospitals, 173 of 488 [35.5%] vs 823 of 2986 [27.6%]; lipid protocols vs none, 451 of 1411 [32.0%] vs 545 of 2063 [26.4%]; both P < .001; cardiology, 523 of 1686 [30.1%] vs internal or family medicine, 377 of 1472 [25.6%] and other, 96 of 316 [30.4%]; P = .003).Conclusions and relevanceOf patients with ASCVD, most with suboptimal LDL-C levels at baseline, only 17.1% had LLT intensification after 2 years, and two-thirds remained at an LDL-C level greater than 70 mg/dL. Further intensive efforts are needed to achieve optimal LDL-C management in patients with ASCVD.

Dataset Information

Time-Dependent Cardiovascular Treatment Benefit Model for Lipid-Lowering Therapies.

Publications

Time-Dependent Cardiovascular Treatment Benefit Model for Lipid-Lowering Therapies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets