Ye-Jee Kim

Differential Cardiovascular Outcomes after Dipeptidyl Peptidase-4 Inhibitor, Sulfonylurea, and Pioglitazone Therapy, All in Combination with Metformin, for Type 2 Diabetes: A Population-Based Cohort Study

Background/Objectives Data on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin. Methods We conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards model weighted for a propensity score. Results During follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI) for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81 (0.67-0.99), respectively. Conclusions Compared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.

β1 selectivity of β-blockers and reduced risk of fractures in elderly hypertension patients

INTRODUCTION Hypertension and osteoporosis are prevalent in the elderly population. Treatments beneficial to both conditions would be helpful. We examined the protective effect of β-blockers (BBs) and their receptor selectivity against fractures compared to other antihypertensives. MATERIALS AND METHODS A retrospective cohort was assembled using the Korean Health Insurance Review and Assessment Service database from January 2005 to June 2006. The cohort consisted of 501,924 patients (ages 65 and older) on single-drug therapy for hypertension. Participants were followed to either the date of the first fracture, date of death or end of the study period (30 June 2006), whichever came first. Coxs proportional hazard model was used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) by sex, adjusting for confounders. Risk of fractures by BBs according to β1 selectivity was compared to non BBs measured in aHR. RESULTS Among 501,924 (65% female), the incidence density of fractures in non BB users was 29.3 and 48.2 per 1000 person-years for men and women, respectively, which was higher than in BB users (17.2 for men and 30.5 for women). Compared to BB users, non BB users showed an increased risk of all fracture [aHR 1.56 (95% CI, 1.42-1.72) in men and 1.44 (95% CI, 1.36-1.51) in women] and hip fracture [aHR 2.17 (95% CI 1.45-3.24) in men and 1.61 (95% CI 1.31-1.98) in women] after adjusting for confounding variables. Compared to BBs, the risks of all fractures in α-blockers, calcium channel blockers, diuretics, and renin-angiotensin-aldosterone system blockers were significantly higher (1.72, 1.77, 1.58, 1.29 in men; 2.11, 1.50, 1.46, 1.22 in women, respectively). Compared to non BBs, β1 selective BBs showed a lower risk of fracture (39% for men and 33% for women) after adjusting for confounding factors. On the contrary, non-selective BBs were not protective against fracture. CONCLUSION Our results suggested that β1 selective BBs reduce the risk of fractures compared to other classes of antihypertensives in an elderly population, which could have practical applications for strategies to control and prevent adverse outcomes from both hypertension and osteoporosis in this population.

Acute renal failure following oral sodium phosphate bowel preparation: a nationwide case-crossover study.

BACKGROUND AND STUDY AIMS Oral sodium phosphate (OSP) is a cleansing agent for colonoscopy. Recent reports have cited an increased risk of acute renal failure (ARF) in OSP bowel purgative users, but this risk remains under debate. This study was performed to evaluate the association between OSP and ARF in patients who underwent colonoscopy. PATIENTS AND METHODS A population-based case-crossover study was conducted using the Korean Health Insurance Review and Assessment Service (HIRA) claims data from 1 January 2005 to 31 December 2009. The study population consisted of patients aged ≥ 50 years who underwent colonoscopies after an OSP prescription prior to their first hospitalization for ARF. For each patient, one hazard and four control periods were matched at specified time windows. Conditional logistic regression analysis was used to estimate the odds ratio (OR) and 95 % confidence interval (CI), adjusting for concomitant medications that could induce ARF. RESULTS A total of 1105 patients were included (54 % male). The adjusted ORs for ARF related to the use of OSP when applying the 1-, 2-, 4-, 8-, or 12-week time windows were 3.7 (95 %CI 2.37 - 5.67), 3.5 (95 %CI 2.45 - 4.89), 3.0 (95 %CI 2.30 - 3.95), 2.4 (95 %CI 1.93 - 2.96), and 2.0 (95 %CI 1.69 - 2.46), respectively. When adopting an 8-week time window, the adjusted OR was 2.5 (95 %CI 1.98 - 3.16) for the subgroup without chronic renal failure. CONCLUSIONS The use of OSP was significantly associated with ARF both in patients with and without co-morbidities.

The Risk of Fracture with Taking Alpha Blockers for Treating Benign Prostatic Hyperplasia.

OBJECTIVES We evaluated the risk of fracture associated with hypotension-related adverse drug reaction caused by taking alpha blockers to treat benign prostatic hyperplasia (BPH). METHODS We used the Health Insurance Review and Assessment Service database from January 1st 2005 to June 30th 2006 for this study. The male patients with BPH and who had a prescription for alpha blockers following any fractures were defined as the cases. We set the 20 day long hazard period prior to the index date and the four control periods whose lengths were same with hazard period. After 1:4 matching of the hazard and control periods, conditional logistic regression was used to calculate the odds ratios for the risk of fractures as related to the alpha blocker exposure. RESULTS Doxazosin and tamsulosin showed the increased risk of fractures, whereas terazosin did not. After stratification using the defined daily doses, a protective effect was shown for the patients who took terazosin at the doses lower than 0.4 DDD and the hazardous effect at the doses higher than or equal to 0.4 DDD. There was no significant difference for the risk of patients taking tamsulosin at the doses higher than 1.0 DDD but there was a statistically significant increase in the risk at the doses higher than or equal to 1.0 DDD. CONCLUSIONS Alpha blockers for BPH may increase the risk of fracture in elderly patients who have comorbidities and take the concomitant medications. Alpha blockers need to be prescribed with caution, although some have high prostate specificity.

Thiazolidinedione use in elderly patients with type 2 diabetes: with and without heart failure

To compare the prescribing patterns of thiazolidinediones (TZDs) in elderly patients with type 2 diabetes with and without heart failure (HF).

Co-Medication of Statins with Contraindicated Drugs

Background The concomitant use of cytochrome P450 3A4 (CYP3A4) metabolized statins (simvastatin, lovastatin, and atorvastatin) with CYP3A4 inhibitors has been shown to increase the rate of adverse events. Objective This study was performed to describe the co-medication prevalence of CYP3A4-metabolized statins with contraindicated drugs. Methods The patients aged 40 or older receiving CYP3A4-metabolized statin prescriptions in 2009 were identified using the national patient sample from a Korea Health Insurance Review and Assessment Service database. Contraindicated co-medication was defined as prescription periods of statins and contraindicated drugs overlapping by at least one day. Co-medication patterns were classified into 3 categories as follows: co-medication in the same prescription, co-medication by the same medical institution, and co-medication by different medical institutions. The proportion of co-medication was analyzed by age, gender, co-morbidities, and the statin’s generic name. Results A total of 2,119,401 patients received CYP3A4-metabolized statins and 60,254 (2.84%) patients were co-medicated with contraindicated drugs. The proportion of co-medication was 4.6%, 2.2%, and 1.8% in simvastatin, lovastatin, and atorvastatin users, respectively. The most frequent combination was atorvastatin-itraconazole, followed by simvastatin-clarithromycin and simvastatin-itraconazole. Among the co-medicated patients, 85.3% were prescribed two drugs by different medical institutions. Conclusion The proportion of co-medication of statins with contraindicated drugs was relatively lower than that of previous studies; however, the co-medication occurring by different medical institutions was not managed appropriately. There is a need to develop an effective system and to conduct outcomes research confirming the association between co-medication and the risk of unfavorable clinical outcomes.