Risk of new acute myocardial infarction hospitalization associated with use of oral and parenteral non-steroidal anti-inflammation drugs (NSAIDs): a case-crossover study of Taiwan's National Health Insurance claims database and review of current evidence.

BACKGROUND: Previous studies have documented the increased cardiovascular risk associated with the use of some nonsteroidal anti-inflammatory drugs (NSAIDs). Despite this, many old NSAIDs are still prescribed worldwide. Most of the studies to date have been focused on specific oral drugs or limited by the number of cases examined. We studied the risk of new acute myocardial infarction (AMI) hospitalization with current use of a variety of oral and parenteral NSAIDs in a nationwide population, and compared our results with existing evidence. METHODS: We conducted a case-crossover study using the Taiwan's National Health Insurance claim database, identifying patients with new AMI hospitalized in 2006. The 1-30 days and 91-120 days prior to the admission were defined as case and matched control period for each patient, respectively. Uses of NSAIDs during the respective periods were compared using conditional logistic regression and adjusted for use of co-medications. RESULTS: 8354 new AMI hospitalization patients fulfilled the study criteria. 14 oral and 3 parenteral NSAIDs were selected based on drug utilization profile among 13.7 million NSAID users. The adjusted odds ratio, aOR (95% confidence interval), for risk of AMI and use of oral and parenteral non-selective NSAIDs were 1.42 (1.29, 1.56) and 3.35 (2.50, 4.47), respectively, and significantly greater for parenteral than oral drugs (p for interaction<0.01). Ketorolac was associated with the highest AMI risk among both of oral and parenteral NSAIDs studied, the aORs were 2.02 (1.00, 4.09) and 4.27 (2.90, 6.29) respectively. Use of oral flurbiprofen, ibuprofen, sulindac, diclofenac, and parenteral ketoprofen were also significantly associated with increased AMI risk. The results of the present study were consistent with the majority of evidence from previous studies. CONCLUSIONS: The collective evidence revealed the tendency of increased AMI risk with current use of some NSAIDs. A higher AMI risk associated with use of parenteral NSAIDs was observed in the present study. Ketorolac had the highest associated risk in both oral and parenteral NSAIDs studied. Though further investigation to confirm the association is warranted, prescribing physicians and the general public should be cautious about the potential risk of AMI when using NSAIDs.

Cancer risk associated with insulin glargine among adult type 2 diabetes patients--a nationwide cohort study.

BACKGROUND: Preclinical and observational studies raise the concern about the safety of insulin glargine in terms of cancer initiation and promotion. This study is designed to examine cancer incidence associated with use of insulin glargine vs. intermediate/long-acting human insulin (HI). METHODOLOGY: A retrospective cohort study using the Taiwan National Health Insurance claims database was conducted to identify adult patients with type 2 diabetes mellitus and without a history of cancer who initiated insulin glargine (n = 10,190) or intermediate/long-acting HI (n = 49,253) during 2004-2007. Exclusive users were followed from the date of insulin initiation to the earliest of cancer diagnosis, death, disenrollment, or December 31 2007. We estimated adjusted hazard ratios and 95% confidence intervals (CIs) with Cox proportional hazards models adjusting for baseline propensity score. FINDINGS: The incidence rate of all cancer per 1,000 person-years was 13.8 for insulin glargine initiators (179 cases) and 16.0 for intermediate/long-acting HI initiators (1,445 cases) during an average follow-up of 2 years. No significant difference in overall cancer risk between insulin glargine initiators and HI initiators was found. For men, however, the adjusted hazard ratio of insulin glargine use as compared with intermediate/long-acting HI was 2.15 (95% CI 1.01-4.59) for pancreatic cancer, and 2.42 (95% CI 1.50-8.40) for prostate cancer. The increased risk was not observed among women. CONCLUSIONS: Insulin glargine use did not increase the risk of overall cancer incidence as compared with HI. The positive associations with pancreatic and prostate cancer need further evaluation and validation.

Risk of hospitalization for upper gastrointestinal adverse events associated with nonsteroidal anti-inflammatory drugs: a nationwide case-crossover study in Taiwan.

PURPOSE: This study aimed to evaluate the risks of upper gastrointestinal (GI) adverse events across a variety of oral and parenteral coxibs and nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in the general population of Taiwan. METHODS: In a case-crossover study, all patients aged ≥20 years who were hospitalized for upper GI adverse events (peptic ulcer and bleeding; gastritis and duodenitis) in 2006 were identified using the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from inpatient claims from the Taiwan National Health Insurance Database. For each patient, the case period was defined as 1-30 days and the control period as 31-60 days before the date of hospitalization. Outpatient pharmacy prescription database was searched for individual NSAID use during the case and control periods. A conditional logistic regression model was applied, and adjusted self-matched odds ratios (OR) and their 95% confidence intervals (95%CI) were reported. RESULTS: A total of 40,635 patients hospitalized for upper GI adverse events were included. The adjusted OR was 1.52 (95%CI: 1.27-1.82) for celecoxib and 2.56 (95%CI: 2.44-2.69) for oral nsNSAIDs. The ORs were above 2 for oral piroxicam, diclofenac, ketorolac, ketoprofen, acemetacin, and naproxen and were around 1.5 for tiaprofenic acid, indomethacin, mefenamic acid, and ibuprofen. Higher risks were evident for parenteral NSAIDs, in particular ketorolac with an OR of 5.76 (95%CI: 5.14-6.44). CONCLUSION: Use of celecoxib and all nsNSAIDs studied was associated with a greater risk of upper GI toxicity as compared with nonuse. Parenteral NSAIDs posed a higher risk, but celecoxib, ibuprofen, and mefenamic acid posed a lower risk than other NSAIDs.

Non-steroidal anti-inflammatory drugs and risk of lower gastrointestinal adverse events: a nationwide study in Taiwan.

OBJECTIVE: Only limited studies have evaluated the risk of non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and coxibs for lower gastrointestinal (GI) adverse outcomes. The objective of this study was to evaluate risks of lower GI adverse events associated with use of celecoxib, oral and parenteral nsNSAIDs. DESIGN: Retrospective case-crossover study. SETTING: Records of all patients aged ≥20 years hospitalised for lower GI adverse events (bleeding from small or large intestine, perforation, and complicated diverticular disease) in 2006 were retrieved using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance database. INTERVENTIONS: Case periods were defined for each patient as 1-30 days prior to hospital admission date and control period as 91-120 days prior to hospital admission date. The pharmacy prescription database was searched for NSAID use during case and control periods. MAIN OUTCOME MEASURES: We calculated adjusted self-matched ORs and 95% CIs with a conditional logistic regression model to determine the associations between NSAID use and lower GI adverse outcomes. RESULTS: A total of 1297 patients hospitalised for lower GI adverse events were included. Celecoxib was associated with an adjusted OR of 2.33 (95% CI 0.97 to 5.59); the association became statistically significant (OR: 3.26, 95% CI 1.07 to 9.91) when a different control period (31-60 days) was applied. Both oral and parenteral nsNSAIDs significantly increased risk for lower GI adverse events (OR: 2.26, 95% CI 1.78 to 2.85 and OR: 5.64, 95% CI 3.24 to 9.82, respectively). CONCLUSIONS: Oral and parenteral NSAIDs were associated with significantly increased risk for lower GI adverse events. Celecoxib also increased risk to a comparable extent, despite risk estimates being affected slightly by the control period chosen for comparison. The association of NSAIDs with specific lower GI adverse events and long-term complications requires further investigation.

Increased risk of stroke associated with nonsteroidal anti-inflammatory drugs: a nationwide case-crossover study.

BACKGROUND AND PURPOSE: Limited studies assessed cerebrovascular safety of individual nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the risk of ischemic and hemorrhagic stroke associated with short-term use of selective and nonselective NSAIDs in a Chinese population with a high incidence of stroke. METHODS: A retrospective case-crossover study was conducted by analyzing the Taiwan National Health Insurance Database. We identified all ischemic and hemorrhagic stroke patients in 2006, aged >or=20 years, based on International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined case period as 1 to 30 days before the index date and control period as 91 to 120 days before the index date. A pharmacy prescription database was searched for NSAID use during the case and control periods. We calculated adjusted ORs and their 95% CIs with a conditional logistic regression model. RESULTS: A total of 28 424 patients with ischemic stroke and 9456 patients with hemorrhagic stroke were included. For ischemic stroke, a modest increased risk was evident for all oral NSAIDs with adjusted ORs (95% CI) ranging from 1.20 (1.00 to 1.44) for celecoxib to 1.90 (1.39 to 2.60) for ketorolac. For hemorrhagic stroke, oral ketorolac was associated with a significantly higher risk with OR of 2.69 (1.56 to 4.66). Significantly increased risk was found for parenteral NSAIDs, in particular ketorolac, with an OR of 3.92 (3.25 to 4.72) for ischemic stroke and 5.98 (4.40 to 8.13) for hemorrhagic stroke. CONCLUSIONS: Use of selective and nonselective NSAIDs was associated with an increased risk of both ischemic and hemorrhagic stroke, strikingly high for parenteral ketorolac.

Cost of chronic hepatitis B virus infection in Taiwan.

GOALS: To estimate the direct medical costs involved in the treatment of chronic hepatitis B (CHB) patients in Taiwan from a public resource perspective. BACKGROUND: Taiwan is a hepatitis B virus (HBV)-hyperendemic area that has considerable expertise in conducting hepatitis studies. To date, however, these studies have focused on basic science or clinical research associated with hepatitis B, and little attention has been paid to the social and monetary consequences of treatment and vaccination programs in Taiwan. STUDY: Total per-patient annual costs were calculated for each of five disease states associated with hepatitis B infection. METHOD: Claims data of National Health Insurance in 2000 were used to identify patients with CHB and to estimate breakdown costs of their medical usage. Medical costs included hospital admissions and outpatient visits, with fees being reimbursed by the National Health Insurance system and patient co-payments. RESULTS: The average total costs per patient for each disease state in the year 2000 were as follows: CHB without cirrhosis, 4905 new Taiwan dollars (NT dollars); compensated cirrhosis, NT 6,574 dollars; decompensated cirrhosis, NT 36,621 dollars; hepatocellular carcinoma, NT 95,741 dollars; and liver transplantation, NT 199,725 dollars. These values indicate that, as the disease progresses, the cost of medical care increases significantly. CONCLUSION: The total inpatient cost for CHB infection in Taiwan for the year 2000 was almost NT 800 million dollars, which accounts for approximately 1% of the total inpatient expenditure. CHB is a significant burden on the Taiwanese healthcare system that could be limited by slowing or reversing liver disease progression.