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Khunti_K_Association of a combined measure of adherence and treatment_JAMA Network Open_Dec 2018.pdf (1.97 MB)

Association of a Combined Measure of Adherence and Treatment Intensity With Cardiovascular Outcomes in Patients With Atherosclerosis or Other Cardiovascular Risk Factors Treated With Statins and/or Ezetimibe.

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posted on 2019-06-27, 15:03 authored by K Khunti, MD Danese, L Kutikova, D Catterick, F Sorio-Vilela, M Gleeson, SR Kondapally Seshasai, J Brownrigg, KK Ray
Importance: Both adherence and treatment intensity can alter the effectiveness of lipid-lowering therapy in routine clinical practice. Objective: To evaluate the association of adherence and treatment intensity with cardiovascular outcomes in patients with documented cardiovascular disease (CVD), type 2 diabetes without CVD or chronic kidney disease (CKD), and CKD without CVD. Design, Setting, and Participants: Retrospective cohort study using the Clinical Practice Research Datalink from January 2010 through February 2016. United Kingdom primary care was the setting. Participants were newly treated patients who received their first statin and/or ezetimibe prescription between January 1, 2010, and December 31, 2013, plus an additional prescription for statins and/or ezetimibe during the following year. Exposures: Adherence was assessed annually using the proportion of days covered, with adherent defined as a proportion of days covered of 80% or higher. Treatment intensity was classified according to guidelines based on the expected percentage of low-density lipoprotein cholesterol (LDL-C) reduction as low (<30% reduction), moderate (30% to <50% reduction), or high (≥50% reduction). Adherence and treatment intensity were multiplied to create a combined measure, reflecting treatment intensity after accounting for adherence. Main Outcomes and Measures: Composite end point of cardiovascular death or hospitalization for myocardial infarction, unstable angina, ischemic stroke, heart failure, or revascularization. Hazard ratios (HRs) were estimated against patients not treated for 1 year or longer. Results: Among a total of 29 797 newly treated patients, there were 16 701, 12 422, and 674 patients with documented CVD, type 2 diabetes without CVD or CKD, and CKD without CVD, respectively; mean (SD) ages were 68.3 (13.2), 59.3 (12.4), and 67.3 (15.1) years, and male proportions were 60.6%, 55.0%, and 47.0%. In the documented CVD cohort, patients receiving high-intensity therapy were more likely to be adherent over time (84.1% in year 1 and 72.3% in year 6) than patients receiving low-intensity therapy (57.4% in year 1 and 48.4% in year 6). Using a combined measure of adherence and treatment intensity, a graded association was observed with both LDL-C reduction and CVD outcomes: each 10% increase in the combined measure was associated with a 10% lower risk (HR, 0.90; 95% CI, 0.86-0.94). Adherent patients receiving a high-intensity regimen had the lowest risk (HR, 0.60; 95% CI, 0.54-0.68) vs patients untreated for 1 year or longer. Findings in the other 2 cohorts were similar. Conclusions and Relevance: Results of this study demonstrate that the lowest cardiovascular risk was observed among adherent patients receiving high-intensity therapy, and the highest cardiovascular risk was observed among nonadherent patients receiving low-intensity therapy. Strategies that improve adherence and greater use of intensive therapies could substantially improve cardiovascular risk.


This study was funded by Amgen Europe GmbH. Dr Khunti’s participation was supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care in East Midlands and the Leicester Biomedical Research Centre.



JAMA Network Open, 2018;1(8):e185554

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SUPPLEMENT. eMethods. Supplemental Methods eTable 1. Estimated Percent LDL-C Change for the Continuous Measure of Treatment Intensity eTable 2. Codes Used to Define Outcomes eTable 3. Distribution of Cardiovascular Risk Factors in Documented CVD Cohort (n = 16,701) eTable 4. Composite Annual Rate of Cardiovascular Events by Cohort eTable 5. Individual Cardiovascular Event Counts and Event Rates for Each Component of the Composite End Point by Cohort eTable 6. Sample Sizes for Groups Defined by Adherence and Intensity Over Study Follow-up eFigure 1. Study Design eFigure 2. Attrition During Cohort Creation Process eFigure 3. Cumulative Number of Cardiovascular Events for Actual and Optimal Adherence and Intensity by Cohort eReferences.



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