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Association of Statin and Its Lipophilicity With Cardiovascular Events in Patients Receiving Chronic Dialysis.

ABSTRACT: Lipophilicity of statins has been linked to extrahepatic cell penetration and inhibition of isoprenoid synthesis and coenzyme Q10, which may affect myocardial contraction. Whether statins' lipophilicity affects the risk of cardiovascular disease development in patients under dialysis is unclear. This population-based study included 114,929 patients undergoing chronic dialysis, retrieved from the Registry for Catastrophic Illness Patients from the National Health Insurance Research Database in Taiwan from 2000 to 2013. Statins were initiated after dialysis and classified into hydrophilic and lipophilic by the duration of use. In total, 17,015 statin users and match controls were identified by using propensity score matching in 1:1 ratio. New statin use was associated with higher cardiovascular disease risk (adjusted hazard ratio (aHR): 1.2, 95% confidence interval (CI), 1.13-1.28) but lower all-cause mortality (aHR: 0.93, 95% CI, 0.89-0.96). Hydrophilic statins were significantly associated with lower risk of cardiovascular disease compared with lipophilic statins (aHR: 0.91, 95% CI, 0.85-0.97).

SUBMITTER: Wang SW

PROVIDER: S-EPMC7325317 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Association of Statin and Its Lipophilicity With Cardiovascular Events in Patients Receiving Chronic Dialysis.

Wang Shih-Wei SW Li Lung-Chih LC Su Chien-Hao CH Yang Yao-Hsu YH Hsu Tsuen-Wei TW Hsu Chien-Ning CN

Clinical pharmacology and therapeutics 20191218 6

Lipophilicity of statins has been linked to extrahepatic cell penetration and inhibition of isoprenoid synthesis and coenzyme Q10, which may affect myocardial contraction. Whether statins' lipophilicity affects the risk of cardiovascular disease development in patients under dialysis is unclear. This population-based study included 114,929 patients undergoing chronic dialysis, retrieved from the Registry for Catastrophic Illness Patients from the National Health Insurance Research Database in Ta ...[more]

PMID: 31715017

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Project description:BackgroundChronic kidney disease (CKD) is a risk factor for cardiovascular disease. The Kidney Disease Improving Global Outcomes 2013 guidelines and the Canadian Cardiovascular Society 2016 guidelines recommend statins for primary prevention of cardiovascular disease in CKD patients aged 50 years or older who are not receiving treatment with kidney transplant or dialysis.ObjectivesTo evaluate statin use for patients in the Vancouver General Hospital Kidney Care Clinic (VGH KCC) and to gain insight into the KCC nephrologists' practices and perspectives regarding the prescribing of statins for patients with CKD.MethodsThe study comprised 2 parts. Part 1 consisted of a cross-sectional study of all statin-eligible patients in the VGH KCC followed by a retrospective chart review. In the chart review, data were collected for 250 statin users and 250 non-users. Logistic regression analyses were performed to determine associations between demographic variables and statin use or non-use. Part 2 was an electronic survey of VGH KCC nephrologists.ResultsOf the 813 statin-eligible patients, 512 (63%) were taking a statin. Patients were approximately 5 times more likely to be receiving statin therapy when it was indicated for secondary versus primary prevention (adjusted odds ratio 4.64, 95% confidence interval 2.95-7.47). Eight of the 9 KCC nephrologists completed the survey, and 7 (87.5%) of these respondents indicated that they never or rarely prescribed statins themselves to KCC patients for primary prevention. However, the same number reported that they sometimes or often suggested statin initiation to family physicians. Three of the respondents indicated agreement with guideline recommendations, but many stated that the decision for statin initiation should be individualized to the patient. Strategies to improve statin prescribing rates that were endorsed by respondents included educating family physicians, creating preprinted orders and laboratory requisitions for statin initiation, providing educational materials about statins to patients, and implementing a protocol for KCC pharmacists to counsel patients about statins.ConclusionsMany statin-eligible VGH KCC patients were not receiving statin therapy, and most of the KCC nephrologists considered statin prescribing as a role for family physicians. Within the KCC, future directions will be to develop a standardized approach to identify patients who would benefit from statin therapy, and to implement strategies to improve statin prescribing rates in appropriate patients.

Project description:Background Statins are commonly used for the prevention of cardiovascular events; however, statins are underutilized in patients with noncoronary atherosclerosis. We sought to establish the rates of statin use in patients with carotid artery disease and to examine the association between statin therapy and outcomes after carotid revascularization. Methods and Results In this population-level retrospective cohort study, we identified all individuals aged ≥66 years who underwent carotid endarterectomy or stenting in Ontario, Canada (2002-2014). The primary outcome was a composite of 1-year stroke, myocardial infarction, or death (major adverse cardiac and cerebrovascular events). Five-year risks were also examined. Adjusted hazard ratios were computed using inverse probability of treatment weighting based on propensity scores. A total of 7893 of 10 723 patients (73.6%) who underwent carotid revascularization were on preprocedural statin therapy; moderate- or high-dose therapy was utilized by 7384 patients (68.9%). The composite rate of 1-year major adverse cardiac and cerebrovascular events was lower among statin users (adjusted hazard ratio: 0.76; 95% confidence interval, 0.70-0.83). Patients who were on persistent long-term statin therapy after the carotid procedure continued to experience significantly lower risk of major adverse cardiac and cerebrovascular events at 5 years (adjusted hazard ratio: 0.75, 95% confidence interval, 0.71-0.80). The beneficial associations with statin use were observed regardless of type of carotid revascularization procedure, carotid artery symptom status, or statin dose. Conclusions Continuous statin therapy was associated with a 25% lower risk of long-term adverse cardiovascular events in patients with significant carotid disease. Along with other supportive evidence, statins should be considered in patients undergoing carotid revascularization, and efforts are required to increase statin use in this undertreated population.

Project description:Background and objectivesCardiovascular (CV) disease is the main cause of morbidity and mortality in patients suffering from chronic kidney disease (CKD). Although it is widely recognized that CV risk assessment represents an essential prerequisite for clinical management, existing prognostic models appear not to be entirely adequate for CKD patients. We derived a literature-based, naïve-bayes model predicting the yearly risk of CV hospitalizations among patients suffering from CKD, referred as the CArdiovascular, LIterature-Based, Risk Algorithm (CALIBRA).MethodsCALIBRA incorporates 31 variables including traditional and CKD-specific risk factors. It was validated in two independent CKD populations: the FMC NephroCare cohort (European Clinical Database, EuCliD®) and the German Chronic Kidney Disease (GCKD) study prospective cohort. CALIBRA performance was evaluated by c-statistics and calibration charts. In addition, CALIBRA discrimination was compared with that of three validated tools currently used for CV prediction in CKD, namely the Framingham Heart Study (FHS) risk score, the atherosclerotic cardiovascular disease risk score (ASCVD), and the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator. Superiority was defined as a ΔAUC>0.05.ResultsCALIBRA showed good discrimination in both the EuCliD® medical registry (AUC 0.79, 95%CI 0.76-0.81) and the GCKD cohort (AUC 0.73, 95%CI 0.70-0.76). CALIBRA demonstrated improved accuracy compared to the benchmark models in EuCliD® (FHS: ΔAUC=-0.22, p<0.001; ASCVD: ΔAUC=-0.17, p<0.001; INDANA: ΔAUC=-0.14, p<0.001) and GCKD (FHS: ΔAUC=-0.16, p<0.001; ASCVD: ΔAUC=-0.12, p<0.001; INDANA: ΔAUC=-0.04, p<0.001) populations. Accuracy of the CALIBRA score was stable also for patients showing missing variables.ConclusionCALIBRA provides accurate and robust stratification of CKD patients according to CV risk and allows score calculations with improved accuracy compared to established CV risk scores also in real-world clinical cohorts with considerable missingness rates. Our results support the generalizability of CALIBRA across different CKD populations and clinical settings.

Project description:ImportanceDe novo statin therapy in patients receiving chronic dialysis has failed to demonstrate cardiovascular (CV) protection in randomized clinical trials and thus is not recommended by current guidelines. However, current guidelines recommend the continuation of statin therapy if initiated before transition to dialysis.ObjectiveTo investigate whether the continuation of statins from advanced chronic kidney disease into the dialysis therapy period is associated with improved survival.Design, setting, and participantsRetrospective cohort study of US veterans transitioning to dialysis between October 1, 2007, and March 30, 2014. Participants were 14 298 US veterans who were receiving statins during the 12-month period before transition to dialysis and survived the first year of dialysis. Data analysis was conducted between August 2, 2017, and June 28, 2018.ExposuresPatients were characterized as statin continuers (n = 11 936) if statin therapy was continued for at least 6 months during the first year after dialysis initiation and as statin discontinuers (n = 2362) if therapy with statins was stopped or no statin therapy was received in the year posttransition.Main outcomes and measuresAssociations of statin continuation with 12-month all-cause mortality and CV mortality after 1 year of dialysis initiation were examined using Cox proportional hazards regression models adjusted for demographics and comorbidities.ResultsThe mean (SD) age of the cohort was 71 (10) years; the cohort was 96.7% (n = 13 828) male and 21.3% (n = 3043) African American, and 74.6% (n = 10 627) had diabetes. The 12-month all-cause mortality and CV mortality rates after 1 year of transition to dialysis were lower in statin continuers: deaths per 100 person-years were 21.9 (95% CI, 20.9-22.8) and 8.1 (95% CI, 7.5-8.6) in statin continuers vs 30.3 (95% CI, 27.8-32.8) and 9.8 (95% CI, 8.3-11.2) in statin discontinuers. Moreover, lower all-cause mortality and CV mortality risks with statin continuation persisted in adjusted analyses, with hazard ratios of 0.72 (95% CI, 0.66-0.79) and 0.82 (95% CI, 0.69-0.96), respectively. Associations were similar across subgroups, including age, race, and diabetes status.Conclusions and relevanceIn this study, the continuation of statin therapy after transition to dialysis was associated with reduced all-cause mortality and CV mortality. The study findings suggest that future studies are needed to examine potential CV benefits of continuing statin therapy after dialysis initiation.

Dataset Information

Association of Statin and Its Lipophilicity With Cardiovascular Events in Patients Receiving Chronic Dialysis.

Publications

Association of Statin and Its Lipophilicity With Cardiovascular Events in Patients Receiving Chronic Dialysis.

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