Studies of non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events using administrative data require identification of incident acute myocardial infarctions (AMIs) and information on whether confounders differ by NSAID status.
We identified patients with a first AMI hospitalization from Tennessee Medicaid files as those with primary ICD-9 discharge diagnosis 410.x and hospitalization stay of > 2 calendar days. Eligible persons were non-institutionalized, aged 50-84 years between 1999-2004, had continuous enrollment and no AMI, stroke, or non-cardiovascular serious medical illness in the prior year. Of 5524 patients with a potential first AMI, a systematic sample (n = 350) was selected for review. Using defined criteria, we classified events using chest pain history, EKG, and cardiac enzymes, and calculated the positive predictive value (PPV) for definite or probable AMI.
337 of 350 (96.3%) charts were abstracted and 307 (91.1%), 6 (1.8%), and 24 (7.1%) events were categorized as definite, probable, and no AMI, respectively. PPV for any definite or probable AMI was 92.8% (95% CI 89.6-95.2); for an AMI without an event in the past year 91.7% (95% CI 88.3-94.2), and for an incident AMI was 72.7% (95% CI 67.7-77.2). Age-adjusted prevalence of current smoking (46.4% vs. 39.1%, p = 0.35) and aspirin use (36.9% vs. 35.9%, p = 0.90) was similar among NSAID users and non-users
ICD-9 code 410.x had high predictive value for identifying AMI. Among those with AMI, smoking and aspirin use was similar in NSAID exposure groups, suggesting these factors will not confound the relationship between NSAIDs and cardiovascular outcomes.
"Validated coding algorithms for the outcomes were selected when available in the literature. For example, ICD-9 codes for incident MI and stroke have been validated against medical charts with high positive predictive values [26, 27]. To verify the findings based on incident cases of bladder cancer, a secondary analysis was performed using additional therapy codes and procedures to confirm the presence of cancer, such as radiation treatment, chemotherapy, cystoscopy or cystectomy. "
[Show abstract][Hide abstract] ABSTRACT: Diabetes is an important global disease, associated with significant morbidity and an increased risk of death due to chronic end-organ complications. The thiazolidinediones, used mainly as third-line agents in type 2 diabetes mellitus (T2DM), have been associated with some safety concerns, such as an increased risk of bladder cancer, an increased risk of bone fracture and heterogeneous effects on cardiovascular events.
This study aimed to evaluate safety data on pioglitazone for several outcomes and examine them in context with each other as well as with insulin, another third-line treatment for T2DM.
This retrospective cohort study extracted data from May 1, 2000 until June 30, 2010, from the i3 InVision Data Mart™ database. To adjust for the testing of multiple hypotheses, the Holm method was applied to endpoints representing potential harm from pioglitazone treatment, separately from those representing potential benefit from pioglitazone. The study population included patients with T2DM ≥ 45 years old who were new users of either pioglitazone or insulin. Key outcomes were incident cases of a composite of myocardial infarction (MI) or stroke requiring hospitalization; bone fracture requiring hospitalization; bladder cancer; and a composite of nine other selected cancers. Kaplan-Meier curves were generated and hazard ratios (HRs) for pioglitazone versus insulin were estimated from Cox proportional hazards models adjusted with inverse probability of treatment weights derived from propensity scores.
A total of 56,536 patients (pioglitazone group 38,588; insulin group 17,948) qualified for the study. The mean follow-up was 2.2 years for pioglitazone and 1.9 years for insulin patients. Weighted survival analysis of the composite of MI and stroke, as well as the composite of nine cancers, yielded significant differences in favour of pioglitazone. For the composite of MI and stroke, the HR for pioglitazone versus insulin was 0.44 (95 % confidence interval [CI] 0.39-0.50, p < 0.0001). Modelling of the composite of nine selected cancers produced an HR of 0.78 (95 % CI 0.71-0.85, p < 0.0001). A non-statistically significant difference in favour of pioglitazone was observed in the incidence rate of bone fracture requiring hospitalization (HR 0.86, 95 % CI 0.74-1.01, p = 0.058). For bladder cancer, the overall incidence rates were relatively low and showed no significant difference between the two groups; the HR for pioglitazone versus insulin was 0.92 (95 % CI 0.63-1.33, p = 0.64).
Compared with insulin, pioglitazone was associated with a significant reduction in the risk of MI and stroke requiring hospitalization, and a significant reduction in the risk of other selected cancers. While pioglitazone treatment may be linked with a lower risk of bladder cancer and bone fracture relative to insulin, these differences were not statistically significant.
Clinical Drug Investigation 07/2013; 33(9). DOI:10.1007/s40261-013-0106-9 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proton-pump inhibitors (PPIs) and clopidogrel are frequently coprescribed, although the benefits and harms of their concurrent use are unclear.
To examine the association between concurrent use of PPIs and clopidogrel and the risks for hospitalizations for gastroduodenal bleeding and serious cardiovascular disease.
Retrospective cohort study using automated data to identify patients who received clopidogrel between 1999 through 2005 after hospitalization for coronary heart disease.
Tennessee Medicaid program.
20,596 patients (including 7593 concurrent users of clopidogrel and PPIs) hospitalized for myocardial infarction, coronary artery revascularization, or unstable angina pectoris.
Baseline and follow-up drug use was assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious cardiovascular disease (fatal or nonfatal myocardial infarction or sudden cardiac death, stroke, or other cardiovascular death).
Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7 to 36.9) hospitalizations for gastroduodenal bleeding per 1000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) for the entire cohort and 1.01 (CI, 0.76 to 1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization.
Unmeasured confounding and misclassification of exposure (no information on adherence or over-the-counter use of drugs) and end points (not confirmed by medical record review) were possible. Because many patients entered the cohort from hospitals with relatively few cohort members, the analysis relied on the assumption that after adjustment for observed covariates, PPI users from one such hospital could be compared with nonusers from a different hospital.
In patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with reduced incidence of hospitalizations for gastroduodenal bleeding. The corresponding point estimate for serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk.
Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute.
Annals of internal medicine 03/2010; 152(6):337-45. DOI:10.1059/0003-4819-152-6-201003160-00003 · 17.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies have suggested that the use of rosiglitazone may be associated with an increased risk of serious cardiovascular events compared with other treatments for type 2 diabetes.
To determine if the risk of serious cardiovascular harm is increased by rosiglitazone compared with pioglitazone, the other thiazolidinedione marketed in the United States.
Nationwide, observational, retrospective, inception cohort of 227,571 Medicare beneficiaries aged 65 years or older (mean age, 74.4 years) who initiated treatment with rosiglitazone or pioglitazone through a Medicare Part D prescription drug plan from July 2006-June 2009 and who underwent follow-up for up to 3 years after thiazolidinedione initiation.
Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference.
A total of 8667 end points were observed during the study period. The adjusted hazard ratio for rosiglitazone compared with pioglitazone was 1.06 (95% confidence interval [CI], 0.96-1.18) for AMI; 1.27 (95% CI, 1.12-1.45) for stroke; 1.25 (95% CI, 1.16-1.34) for heart failure; 1.14 (95% CI, 1.05-1.24) for death; and 1.18 (95% CI, 1.12-1.23) for the composite of AMI, stroke, heart failure, or death. The attributable risk for this composite end point was 1.68 (95% CI, 1.27-2.08) excess events per 100 person-years of treatment with rosiglitazone compared with pioglitazone. The corresponding number needed to harm was 60 (95% CI, 48-79) treated for 1 year.
Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older.
JAMA The Journal of the American Medical Association 07/2010; 304(4):411-8. DOI:10.1001/jama.2010.920 · 35.29 Impact Factor
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