Development and application of an algorithm for statin-induced myopathy based on electronic health record-derived structured elements.

Objective: Considering the non-specific nature of muscle symptoms, studies of statin-induced myopathy (SIM) in electronic health records require accurate algortihms that can reliably identify true statin-related cases. However, prior algorithms have been constructed in study populations that preclude broad applicability. Here we developed and validated an algorithm that accurately defines SIM from electronic health records using structured data elements and conducted a study of determinants of SIM after applying the algorithm. Materials and Methods: We used electronic records from an integrated health care delivery system (including comprehensive pharmacy dispensing records) and defined SIM as elevated creatine kinase (CK) ≥4 x upper limit of normal. A diverse cohort of participants receiving a variety of statin regimens met the criteria for study inclusion. Results: We identified multiple conditions strongly associated with elevated CK independent of statin use. A 2-step algorithm was developed using these all-cause conditions as secondary causes (step 1) along with evidence of a statin regimen change (step 2). We identified 1,262 algorithm-derived statin-induced elevated CK cases. Gold standard SIM cases determined from manual chart reviews on a random subset of the all-cause elevated CK cases were used to validate the algorithm, which had a 76% sensitivity and 77% specificity for detecting the most certain cases. Pravastatin use was associated with a 2.18 odds (95% confidence interval 1.39-3.40, P=0.0007) for statin-induced CK elevation compared to lovastatin use after adjusting for dose and other factors. Conclusions: We have produced an efficient, easy-to-apply methodological tool that can improve the quality of future research on statin-induced myopathy.

Nonutilization of Statins in a Community-based Population with a History of Coronary Revascularization.

PURPOSE: Statin therapy has been reported to reduce the incidence of vascular events in patients with atherosclerosis, but adherence to statins may be suboptimal. The aims of this study were to quantify the rate of statin use among individuals with a history of coronary revascularization in a large, integrated health care system and to determine which demographic characteristics and clinical factors are associated with statin use. METHODS: This was a retrospective cohort study using database programming and chart review. The study included adult members of Kaiser Permanente Northern California with a history of coronary revascularization. The study outcome was off-statin status, defined as a ≥1-year gap between filled prescriptions. The predictor variables included age, race, body mass index, dyslipidemia, liver disease, kidney disease, and history of statin allergy. Multivariable logistic regression was used to quantify the associations between the predictor variables and statin status. A chart review of a randomly selected subset was performed to identify reasons why individuals were not taking statins. FINDINGS: The study population included 17,869 Kaiser Permanente Northern California members, of which 18.3% had off-statin status. The following variables were associated with off-statin status: statin allergy (odds ratio [OR] = 2.18; 95% CI, 1.89-2.52), end-stage renal disease (OR = 1.55; 95% CI, 1.26-1.91), liver disease (OR = 1.44; 95% CI, 1.08-1.93), African-American race (OR = 1.55 vs white; 95% CI, 1.32-1.81), and Latino race (OR = 1.18; 95% CI, 1.05-1.33). The chart review found that off-statin status typically reflects patient (79%) rather than provider (21%) preference. IMPLICATIONS: A significant minority of patients with a history of coronary revascularization are not taking statins. Off-statin status is associated with kidney disease, liver disease, African-American race, and Latino race. At an individual level, off-statin status was usually driven by patient preference, due to minor or undefined reasons. These findings may be useful in guiding strategies to increase statin use in individuals with atherosclerosis.

Short QT in a cohort of 1.7 million persons: prevalence, correlates, and prognosis.

BACKGROUND: Short QT syndrome (QTc ≤ 300 ms) is a novel hereditary channelopathy linked to syncope, paroxysmal atrial fibrillation, and sudden cardiac death. However, its epidemiological features remain unsettled. OBJECTIVES: (1) To assess the prevalence of short QT in a large population-based sample; (2) to evaluate its demographic and clinical correlates and; (3) to determine its prognosis. METHODS: A database of 6.4 million electrocardiograms (ECGs) obtained between 1995 and 2008 among 1.7 million persons was used. An internal, population-based method for heart rate correction (QTcreg ) was used and all ECGs with QTcreg ≤300 ms were manually validated. Linked health plan databases were used for covariate and survival ascertainment. RESULTS: Of 6,387,070 ECGs, 1086 had an ECG with machine-read QTcreg ≤300 ms. Only 4% (45/1086) were validated yielding a prevalence of 0.7 per 100,000 or 1 of 141,935 ECGs. At the person level, the overall prevalence of QTcreg ≤300 ms was 2.7 per 100,000 or 1 of 37,335. The factors independently and significantly associated with validated QTcreg ≤300 ms were age over 65 years, Black race, prior history of ventricular dysrhythmias, chronic obstructive pulmonary disease, ST-T abnormalities, ischemia, bigeminy pattern, and digitalis effect. After 8.3 years of median follow-up and relative to normal QTcreg , validated QTcreg ≤300 ms was associated after multivariate adjustment with a 2.6-fold (95% confidence interval [CI] = 1.9-3.7) increased risk of death. CONCLUSION: QTcreg ≤300 ms was extraordinarily rare and was associated with significant ECG abnormalities and reduced survival.

Validation of a population-based method to assess drug-induced alterations in the QT interval: a self-controlled crossover study.

PURPOSE: The purpose of this study was to ascertain, in the context of an integrated health care delivery system, the association between a comprehensive list of drugs known to have potential QT liability and QT prolongation or shortening. METHODS: By using a self-controlled crossover study with 59 467 subjects, we ascertained intra-individual change in log-linear regression-corrected QT (QTcreg ) during the period between 1995 and mid-2008 for 90 drugs while adjusting for age, gender, race/ethnicity, comorbid conditions, number of electrocardiograms (ECGs), and time between pre-ECG and post-ECG. The proportion of users of each drug-developing incident long QT was also estimated. RESULTS: Two drugs (nicardipine and levalbuterol) had no statistically significant intra-individual QTcreg shortening effects, 10 drugs had no statistically significant prolonging effect, and 78 (87%) of the drugs had statistically significant intra-individual mean QTcreg lengthening effects, ranging from 7.6 ms for aripiprazole to 25.2 ms for amiodarone. Three drugs were associated with mean QTcreg prolongation of 20 ms or greater: amiodarone (antiarrhythmic), terfenadine (antihistaminic), and quinidine (antiarrhythmic); whereas 11 drugs were associated with mean QTcreg prolongation of 15 ms or greater but less than 20 ms: trimipramine (tricyclic antidepressant), clomipramine (tricyclic antidepressant), disopyramide (antiarrhythmic), chlorpromazine (antipsychotic), sotalol (beta blocker), itraconazole (antifungal), phenylpropanolamine (decongestant/anorectic), fenfluramine (appetite suppressant), midodrine (antihypotensive), digoxin (cardiac glycoside/antiarrhythmic), and procainamide (antiarrhythmic). CONCLUSIONS: QT prolonging effects were common and varied in strength. Our results lend support to past Food and Drug Administration regulatory actions and support the role for ongoing surveillance of drug-induced QT prolongation.