Andrew T. McAfee

Pharmacoepidemiology Safety Study of Fibrate and Statin Concomitant Therapy

Combinations of statins and fibrates may be increasingly prescribed to achieve lipid goals in high-risk patients and those with other cardiovascular risk factors, such as mixed dyslipidemia. The purpose of this retrospective cohort study was to compare rates of hospitalization for specific diagnoses in a cohort of new users of statins or fibrates, using claims data from a large United States health insurer. New users of statin, fibrate, or statin-fibrate therapy from 2004 to 2007 were identified; followed for hospitalization with rhabdomyolysis, renal impairment, hepatic injury, or pancreatitis; and confirmed by medical record review. Incidence rates (IRs) were compared across categories of fibrate or statin use, with adjusted IR ratios estimated using Poisson regression. A total of 584,784 patients initiated statins or fibrates. The IR of rhabdomyolysis in statins was 3.30 per 100,000 patient-years; the adjusted IR ratio for statin-fenofibrate combinations compared to statins alone was 3.75 (95% confidence interval 1.23 to 11.40). The IRs of renal impairment and pancreatitis in statins were 108.87 per 100,000 patient-years and 45.76 per 100,000 patient-years, respectively; the adjusted IR ratios for statin-fenofibrate combinations compared to statins alone were 1.47 (95% confidence interval 1.12 to 1.93) and 2.87 (95% confidence interval 2.05 to 4.02), respectively. The IR of hepatic injury with statins was 8.57 per 100,000 patient-years, with no risk difference between exposure groups. In conclusion, the risk for rhabdomyolysis was low, although higher in patients newly treated with statin-fibrate concurrent therapy than those treated with either as monotherapy. The risk for pancreatitis was higher in patients treated with fenofibrate, whether in combination with statins or alone.

Coronary heart disease outcomes among chronic opioid and cyclooxygenase-2 users compared with a general population cohort.

We estimated the incidence of myocardial infarction (MI) and coronary revascularization (CR) among users of chronic opioid therapy (COT) and compared risks across categories of morphine‐equivalent doses of COT and comparator cohorts.

Incidence of Hospitalized Rhabdomyolysis with Statin and Fibrate Use in an Insured US Population

Background: The incidence of hospitalized rhabdomyolysis is not well characterized among patients taking statin-fibrate combination therapies. Objective: To estimate and compare the rates of hospitalized rhabdomyolysis during periods of exposure to different statins and fibrates. Methods: We retrospectively identified a cohort patients who initiated a statin or fibrate between January 1, 1998, and December 31, 2007, using a database of a large US hearth insurer. Patients were followed for the occurrence of hospitalized rhabdomyolysis, determined by clinical review of medical records. Exposure status during the study period was determined by electronic records of statin and fibrate dispensing. Incidence rates (IRs) and incidence rate ratios (IRRs) for various combinations of fibrate and statin exposure were modeled, using Poisson regression. Results: There were 1,116,805 patients who initiated statin and/or fibrate therapy, with 2.4 million person-years of observation. Seventy cases of hospitalized rhabdomyolysis were confirmed. Adjusted analyses showed a persistent increased risk of rhabdomyolysis with combination therapy, while statin and fibrate therapy alone showed similar, nonsignificant increases in risk. The adjusted IRR for a statin and fenofibrate was 3.26 (95% CI 1.21 to 8.60), while the adjusted IRR for a statin and gemfibrozil was 11.93 (95% CI 3.96 to 35.93) versus statin therapy alone. The individual IRs for statin monotherapy ranged from 0.00 to 3.34 per 100,000 person-years. The number needed to harm was tower for combination statin-gemfibrozil therapy (2753) compared with that for statin therapy atone (454,545). Conclusions: The incidence of hospitalized rhabdomyolysis is rare, but higher in patients with concomitant statin-fibrate treatment than in patients on statin therapy atone. The rate found in this study is consistent with the known profile of the statin-fibrate treatment option for mixed dyslipidemia.

The thiazolidinediones rosiglitazone and pioglitazone and the risk of coronary heart disease: A retrospective cohort study using a US health insurance database

BACKGROUND The thiazolidinediones (TZDs), including rosiglitazone maleate and pioglitazone hydrochloride, are commonly prescribed in patients with type 2 diabetes mellitus. Although recent meta-analyses suggest there is an increased risk of myocardial infarction (MI) among rosiglitazone users, these findings were not supported by data from other studies. OBJECTIVE The goal of this research was to compare the risk of MI, coronary revascularization (CR), and sudden death in patients who began rosiglitazone therapy versus those who began pioglitazone therapy. METHODS This was a retrospective cohort study using information from a large health care database (with data available on approximately 14 million individuals). All initiators of rosiglitazone or pioglitazone from July 1, 2000, through March 31, 2007, for whom the first dispensing followed >or=6 months of health plan membership and the members 18th birthday were identified. The propensity score method was used to create matched cohorts of patients in 3 treatment groups: TZD monotherapy, dual therapy (a TZD plus another antidiabetic agent), and TZD therapy with concomitant insulin. Follow-up continued to a change in treatment regimen, defined as regimen switch (ie, the addition of any antidiabetic agent to an existing regimen) or regimen stop (ie, the discontinuation of any component of the therapeutic regimen). Three outcomes that represent coronary heart disease were assessed for this analysis: MI, CR, and sudden death. The proportional hazards model, stratified by therapeutic regimen, was used to estimate hazard ratios (HRs) and 95% CIs of coronary heart disease risk associated with use of rosiglitazone relative to pioglitazone. RESULTS Among 47,501 matched pairs of rosiglitazone and pioglitazone users, 72,104 (75.9%) were receiving TZD monotherapy, 17,822 (18.8%) were receiving dual therapy, and 5076 (5.3%) were receiving TZD therapy with insulin. Mean follow-up was 9.6 months with regimen switch as the censoring event and 8.4 months with regimen stop as the censoring event. For MI, the HR was 1.35 (95% CI, 1.12-1.62) through regimen switch and 1.41 (95% CI, 1.13-1.75) through regimen stop. For the composite outcome of MI, CR, and/or sudden death, the HR was 1.09 (95% CI, 0.97-1.22) through regimen switch and 1.12 (95% CI, 0.98-1.27) through regimen stop. CONCLUSIONS In this retrospective cohort analysis, MI was more common in users of rosiglitazone than in users of pioglitazone. The incidence of a combined end point of MI, CR, and/or sudden death in patients receiving rosiglitazone was not significantly different from that in patients receiving pioglitazone.

The incidence of first provoked and unprovoked seizure in pediatric patients with and without psychiatric diagnoses.

Summary:  Purpose: To estimate the rate of new‐onset afebrile provoked and unprovoked seizure in a general pediatric population and subgroups of patients with and without psychiatric diagnoses other than attention deficit hyperactivity disorder (ADHD).

Comorbidities in patients with persistent or chronic immune thrombocytopenia

There is a paucity of epidemiological data on the risk of comorbidities in adults with persistent or chronic immune thrombocytopenia (ITP). In this study, we compared the rates of cataracts, diabetes, renal failure, vascular events, lymphoma, and leukemia among patients with and without persistent or chronic ITP. Using administrative data, adult patients with medical claims for ITP from January, 2000 through September, 2006 were identified. An age- and gender-matched comparison cohort without evidence of ITP was randomly selected. The incidence rate ratio (IRR) of each comorbidity among ITP patients relative to the comparison group was estimated using Poisson regression, adjusting for baseline covariates. A total of 3,131 patients with persistent or chronic ITP were identified, and 9,392 were selected for the comparison cohort. The adjusted IRRs were as follows: diabetes 1.73 (95% CI 1.36–2.20), renal failure 2.05 (95% CI 1.67–2.51), any vascular event 1.70 (95% CI 1.41–2.05), lymphoma 5.91 (95% CI 2.61–13.37), leukemia 19.83 (95% CI 5.84–67.34), and mortality 4.21 (95% CI 3.06–5.79). There was no increased risk for cataract or myocardial infarction in the ITP cohort. Patients with persistent or chronic ITP are at increased risk for several comorbidities including hematologic malignancies, relative to a matched comparison cohort.

Thromboembolic Events Among Patients with Hepatitis C Virus Infection and Cirrhosis: A Matched-Cohort Study

IntroductionPortal vein thrombosis is a known risk among patients with cirrhosis, but the incidence of other thromboembolic events among patients with liver disease is inadequately delineated. This study examined the incidence of venous and arterial thromboembolic events in patients with cirrhosis and hepatitis C virus (HCV) infection and matched comparators.MethodsPatients diagnosed with HCV or cirrhosis of various etiologies were identified from a large medical claims database and matched by age and sex to comparator cohorts. New-onset diagnoses of venous and arterial thromboembolic events were determined. The incidence rate of each event was calculated and rate ratios computed using Poisson regression models, adjusting for baseline factors.ResultsThe study included 22,733 HCV-infected patients and 68,198 comparators, and 15,158 cirrhosis patients and 45,473 comparators. The incidence of any thromboembolic event was 233.4 events per 10,000 person-years for the HCV cohort and 138.5 per 10,000 person-years for the comparators; the adjusted incidence rate ratio for any thromboembolic event was 1.62 (95% confidence interval [CI]: 1.48–1.77). For the cirrhosis patients and comparators, the crude rates of any thromboembolic event were 561.1 and 249.7 per 10,000 person-years, respectively. The adjusted incidence rate ratio was 2.28 (95% CI: 2.11–2.47). Arterial events, especially unstable angina and transient ischemic attack, were the most frequent events seen in both the HCV and cirrhosis cohorts, but venous events, especially portal vein thrombosis, showed a more pronounced elevation in patients with liver disease.ConclusionsPatients with HCV and cirrhosis of various etiologies are at increased risk of several types of thromboembolic events. Physicians should consider this increased risk when managing patients with liver disease.

The Effect of Pharmacotherapy for Attention Deficit Hyperactivity Disorder on Risk of Seizures in Pediatric Patients as Assessed in an Insurance Claims Database

PURPOSE To estimate the rate of new-onset seizure in ADHD patients in relation to ADHD pharmacotherapy. METHODS A retrospective cohort study of 34,727 patients, ages 6 to 17, with at least two insurance claims bearing ADHD diagnoses during 2003 in the UnitedHealthcare database. Incidence of seizure was calculated for observation time during treatment with atomoxetine and stimulants/bupropion. RESULTS Seizure incidence among ADHD patients was 4.5/1,000 person-years (p-y; 95% confidence interval 3.7 - 5.5). ADHD patients who received any ADHD medication had an incidence of 3.8/1,000 p-y (3.0 - 4.8) compared to 8.7 (5.8 - 12.4) for patients who did not receive any ADHD medication. The relative risk (RR) for current vs non-use of atomoxetine was 1.1 (0.6 - 2.1). For stimulants and bupropion, the RR for current vs non-use was 0.8 (0.6 - 1.3). Elevated seizure risks were found in association with central nervous system (CNS) disease (OR 3.9, 1.2 - 10.9), CNS medications (OR 2.2, 1.3 - 3.6), metabolic disease (OR 2.9, 1.1 - 6.8), and psychiatric disease risk factors (OR 1.7, 1.1 - 2.6). CONCLUSIONS In this study, there was no statistically significant association between use of atomoxetine or stimulants and seizure risk in children ages 6 to 17 years with ADHD and without prior seizure disorder.

Panic disorder and emergency services utilization.

OBJECTIVES The characteristics of patients with panic disorder in emergency department (ED) patient populations are unknown. This study compares demographic information and emergency care use among patients identified as having a high likelihood of having panic disorder with that of patients who tested negative on the screening test for panic disorder. METHODS Prospective cross-sectional study of a convenience sample of patients presenting to an urban ED. Patients were excluded if they were aged 18 years or younger, were unstable, or could not speak English or Spanish. Of 968 patients, 813 agreed to participate. Over a period of 23 days, patients were administered a Diagnostic and Statistical Manual (DSM)-IV screening questionnaire (PRIME-MD) for panic disorder along with a survey assessing their use of medical services during the prior year. RESULTS One hundred patients (12.3%) met PRIME-MD criteria for having a high likelihood of panic disorder. Patients with Medicare were 2.84 times more likely to have a positive result on the screening test than those without insurance. Patients who had four to seven ED visits or eight or more ED visits in one year were 2.63 and 3.10 times more likely to screen positive on the PRIME-MD, respectively, compared with those who had one to three visits. Patients who activated 911 two to ten times or 11 or more times in one year were 2.02 and 4.99 times more likely to screen positive for panic disorder, respectively, compared with those who had never activated 911. CONCLUSIONS Patients who screen positive for panic disorder use emergency medical services and ED services more frequently. In addition, the overall prevalence of screening positive for panic disorder in an ED is higher than previously reported.

Prognostic Value of the Duke Treadmill Score for Emergency Department Patients with Chest Pain

BACKGROUND The potential clinical utility of the Duke Treadmill Score (DTS) in the Emergency Department (ED) to risk-stratify patients with chest pain but negative cardiac biomarkers and non-diagnostic electrocardiograms is unclear. OBJECTIVE We evaluated whether DTS was associated with 30-day adverse cardiac outcomes for low-risk ED patients with chest pain. METHODS For this prospective, observational cohort study, the primary outcome was any of the following at 30 days: cardiac death, myocardial infarction, or coronary revascularization. DTS risk categories (low, intermediate, high) were compared with 30-day cardiac outcomes. RESULTS We enrolled 191 patients, of whom 20 (10%) were lost to follow-up, leaving 171 patients (mean age 53.3 +/- 12.4 years, 54% female, 3.5% adverse event rate) for evaluation. Sensitivity and specificity of DTS for 30-day events were 83.3% and 71.5%, respectively, with a 99.2% negative predictive value (confidence interval 95.4-99.9) for 30-day event-free survival. CONCLUSIONS In this cohort of low-risk ED patients with chest pain, DTS demonstrated excellent negative predictive value for 30-day event-free survival and facilitated safe disposition of a large subset of patients.