Zhao Y Y et al. Ann Intern Med 2012;156:

Transcription

1 Zhao Y Y et al. Ann Intern Med 2012;156:

2 Introduction Fibrates are commonly prescribed to treat dyslipidemia An increase in serum creatinine level after use has been observed in randomized, placebocontrolled trials Elderly patients have a high prevalence of dyslipidemia and chronic kidney disease and are frequently excluded from RCT

3 Aim To better characterize acute renal outcomes associated with fibrate use in elderly patients and their effect on health care use

4 Methods Primary objective : to examine the association between a new prescription for fibrate and renal outcomes within 90 days fibrate use would be associated with increased hospitalization for an increase in serum Cr and consultation with a nephrologist Secondary objective : To compared characteristics of patients prescribed fibrates in our population with those enrolled in RCT

5 Design and Setting A population-based cohort study Using linked health care databases in Ontario approximately 13 million residents 14% of whom are aged 65 years Who have universal access to hospital care and physician services, and And have universal prescription drug coverage

6 Data Sources 4 databases 1) The Ontario Drug Benefit Program database accurate records of all outpatient prescriptions dispensed to patients aged 65 years or older, with a basic error rate of less than 1% 2) The Canadian Institute for Health Information Discharge Abstract Database diagnostic and procedural information on all hospitalizations in Ontario 3) The Ontario Health Insurance Plan database all health claims for inpatient and outpatient physician services 4) The Ontario Registered Persons Database demographic and vital status information on all Ontario residents who have ever been issued a health card Each database has been used extensively to research health outcomes and services

7 Participants All elderly residents of Ontario with new prescriptions for a fibrate or ezetimibe aged 66 years to assess baseline medications for a full year before the index date (that is, beginning at age 65 years) From 1 January 2004 to 31 December 2008 Either group could be receiving a statin Ezetimibe was chosen as the comparator drug The date of the first prescription served as the start (index) date of follow-up

8 Participants Patients were followed for 90 days after the index date or until death Exclusion Patients with end-stage renal disease (defined as receipt of dialysis or a kidney transplant in the preceding 5 years) Patients who received a prescription for both ezetimibe and a fibrate on the index date (<0.3% of patients)

9 Study flow diagram.two or more of the exclusion criteria may have applied to certain patients by American College of Physicians Zhao Y Y et al. Ann Intern Med 2012;156:

10 Participants Assess baseline comorbid conditions Measures of health care access, use, and screening in the 5 years before and concurrent drug therapy in the year before the index date To compare characteristics of fibrate users in our cohort with those enrolled in major randomized, placebocontrolled trials published in the past 10 years a PubMed search fibrates + treatment or therapy limits English, human, and clinical trials. Major clinical trials were enrolled more than 1000 patients and reported renal outcomes related to fibrate exposure

11 Outcomes Primary outcome : hospitalization for an increase in serum creatinine level Secondary outcomes : consultation with a nephrologist (either within or outside of a hospital) from the International Classification of Diseases, Tenth Revision (ICD 10 th )

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13 Statistical Analysis Used standardized differences to assess differences in baseline characteristics --a clinically difference if greater than 10% Used a multivariable logistic regression analysis to estimate odds ratios (ORs) and 95% CI and adjusting for 16 covariates Performed a propensity-based analysis on a 1-to- 1 basis from the primary cohort by using 6 variables (age [5 years], sex, statin use, diabetes, chronic kidney disease, and a logit of a propensity score for fibrate use

14 Statistical Analysis Used the Wilcoxon rank-sum test to analyses of change in serum Cr level Used baseline cholesterol or serum triglyceride level and the 16 covariates from the primary analysis as exposure variables and a 50% increase in serum Cr level as the outcome variable Repeated the multivariable logistic regression analysis but restricted the sample to patients with total Chol or serum TG and serum Cr levels measured before prescription subgroup analysis in those with and without chronic kidney disease

15 Statistical Analysis The association of fibrate use and hospitalization for an increase in serum Cr level and nephrology consultation in 3 prespecified subgroups 1. the presence or absence of diabetes mellitus, 2. chronic kidney disease 3. concomitant statin use All analyses by using SAS, version 9.2 (SAS Institute, Cary, North Carolina

16 Role of the Funding Source This study was funded by the Ontario Ministry of Health and Long-Term Care The funding source had no role in the design, conduct, or analyses of the study; the drafting and editing of the article; or the decision to submit for publication The opinions, results, and conclusions are those of the authors and are independent of the funding sources

17 RESULTS

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30 Comparison of change in serum creatinine level among fibrate users and ezetimibe users, by baseline egfr.egfr = estimated glomerular filtration rate by American College of Physicians Zhao Y Y et al. Ann Intern Med 2012;156:

31 90-day changes in serum creatinine level after fibrate use, by baseline egfr.egfr = estimated glomerular filtration rate.* Comparison of changes in serum creatinine level between those with egfr 60 ml/min per 1.73 m2 or higher and those with egfr below 60 m by American College of Physicians Zhao Y Y et al. Ann Intern Med 2012;156:

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36 Discussion