Karen L. Rascati

Temporal Relationship between Use of NSAIDs, Including Selective COX-2 Inhibitors, and Cardiovascular Risk

AbstractBackground and Objective: The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. However, following their introduction into the market, concerns have developed regarding their safety, particularly their cardiovascular safety. The purpose of this study was to assess the cardiovascular risk (events included were myocardial infarction, stroke and myocardial infarction-related deaths) associated with long-term (>180 days of exposure) and short-term (≤180 days of exposure) use of non-selective NSAIDs, including ‘preferential COX-2 inhibitors’ (i.e. etodolac, nabumetone and salsalate), and selective COX-2 inhibitors. Methods: A retrospective analysis of the Veterans Integrated Service Network 17 Veterans Affairs (VA) database was conducted. Medicare data and Texas Department of Health mortality data were incorporated to capture events occurring outside the VA healthcare network. Patients ≥35 years of age who received celecoxib, rofecoxib, ibuprofen, etodolac and naproxen from 1 January 1999 through 31 December 2001, were included. Multivariate Cox proportional hazard models were used to analyse the relationship between cardiovascular risk and NSAID use, including selective COX-2 inhibitor use, while adjusting for various risk factors. Results: We identified 12 188 exposure periods (11 930 persons) and 146 cardiovascular events over the entire study period. Compared with long-term ibuprofen use, long-term use of celecoxib (adjusted hazard ratio [HR] 3.64; 95% CI 1.36, 9.70) and rofecoxib (adjusted HR 6.64; 95% CI 2.17, 20.28) was associated with a significant increase in cardiovascular risk. When restricted to patients ≥65 years of age, the cardiovascular risks associated with long-term celecoxib (adjusted HR 7.36; 95% CI 1.62, 33.48) and rofecoxib (adjusted HR 13.24; 95% CI 2.59, 67.68) use increased. Short-term use of celecoxib (adjusted HR 0.75; 95% CI 0.42, 1.35) and rofecoxib (adjusted HR 0.85; 95% CI 0.39, 1.86) was not associated with any significant change in cardiovascular risk when compared with short-term ibuprofen use. Neither long- nor short-term exposure to naproxen and etodolac was associated with cardionegative or cardioprotective effects when compared with ibuprofen use. Conclusions: The findings of this observational study, along with recent clinical trial results, suggest that prolonged exposure to selective COX-2 inhibitors may be associated with an increased risk of adverse cardiovascular outcomes.

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes: Meta-Analysis

BACKGROUND: An up-to-date assessment of dipeptidyl peptidase-4 (DPP-4) inhibitors is needed to include newly available data. OBJECTIVE: To assess the efficacy and safety of DPP-4 inhibitors, including sitagliptin, saxagliptin, vildagliptin, and linagliptin, in type 2 diabetes. METHODS: We conducted a search of MEDLINE for randomized controlled trials (RCTs) of DPP-4 inhibitors in type 2 diabetes through November 2011, using the key terms sitagliptin, saxagliptin, vildagliptin, and linagliptin. We also searched for completed, but unpublished, trials at relevant web sites. RCTs were selected for meta-analysis if they (1) compared DPP-4 inhibitors with placebo or an antihyperglycemic agent; (2) had study duration of 12 or more weeks; (3) had 1 or more baseline and posttreatment efficacy and/or safety outcome; and (4) were published in English. RESULTS: In 62 evaluated articles, DPP-4 inhibitors lowered hemoglobin A1c (A1C) significantly more than placebo (weighted mean difference [WMD] −0.76%; 95% CI −0.83 to −0.68); however, heterogeneity was substantial (I2 = 82%). Exclusion of Japanese trials (n = 7) resulted in a reduction of heterogeneity (I2 = 59%). In the non-Japanese RCTs (n = 55), DPP-4 inhibitors were associated with a reduction in A1C (WMD −0.65%; 95% CI −0.71 to −0.60) but higher risk of hypoglycemia (odds ratio [OR] 1.30; 95% CI 1.00 to 1.68) compared to placebo. The 7 Japanese-specific RCTs showed a greater reduction in A1C (WMD −1.67%; 95% CI −1.89 to −1.44) and a nonsignificant increase in risk of hypoglycemia (OR 1.41; 95% CI 0.51 to 3.88) with DPP-4 inhibitors versus placebo. When comparing DPP-4 inhibitors to active comparators, the I2 was still high after deleting Japanese studies. In these 17 active comparator trials, there was no significant difference in A1C reduction (WMD 0.04%; 95% CI −0.09 to 0.16) or risk of hypoglycemia (OR 0.60; 95% CI 0.22 to 1.61) for DPP-4 inhibitors compared to other antihyperglycemics. There were similar odds of any or serious adverse events with DPP-4 inhibitors compared to placebo, but a decreased risk compared to other antihyperglycemics. CONCLUSIONS: DPP-4 inhibitors were associated with a reduction in A1C with comparable safety profiles compared to placebo, but no significant difference in A1C compared to other hyperglycemics. Differences in efficacy and safety were observed between Japanese and non-Japanese patients.

Olanzapine versus risperidone in the treatment of schizophrenia : a comparison of costs among Texas Medicaid recipients.

AbstractObjective: To examine both schizophrenia-related costs and total (schizophrenia plus non-schizophrenia) healthcare costs among Texas Medicaid recipients who had been diagnosed with a schizophrenic disorder and had been initiated on olanzapine or risperidone. Methods: Cost data for services and prescription use were retrieved for 2885 patients with schizophrenia who were initiated on olanzapine or risperidone between 1 January 1997 and 31 August 1998. Each patient was followed for 1 year before and 1 year after initiation of therapy. Multivariate analysis was used to control for a wide range of factors (drug choice, patient demographics, pre-utilisation costs, region, health conditions, and treatment patterns) that may influence schizophrenia-related costs and total healthcare costs. Estimation was conducted via a two-stage instrumental variables model. Results: The mean unadjusted total schizophrenia-related cost per patient per year during the observation period was

Drug utilization review of concomitant use of specific serotonin reuptake inhibitors or clomipramine with antianxiety/sleep medications

US4892, and the total unadjusted healthcare cost per patient was

Patterns of antihypertensive use among patients in the US Department of Defense database initially prescribed an angiotensin-converting enzyme inhibitor or calcium channel blocker

US7101. Results revealed significant regional variation in schizophrenia-related and total healthcare costs. Significantly higher total healthcare costs were found for patients with other (nonpsychiatric) diagnoses, such as HIV and diabetes mellitus. Although, on average, patients taking olanzapine stayed on therapy longer than those taking risperidone (248.2 days vs 211.1 days; p < 0.0001), multivariate analysis revealed no significant difference in schizophrenia-related costs between patients who received olanzapine and risperidone (

Inhaled anti-inflammatory pharmacotherapy and subsequent hospitalizations and emergency department visits among patients with asthma in the Texas Medicaid program.

US123 lower with olanzapine; p = 0.6439). However, patients who received olanzapine compared with risperidone had significantly lower total medical costs (

Effects of antiepileptic drug substitutions on epileptic events requiring acute care.

US693 lower with olanzapine; p = 0.0311). Conclusion: This naturalistic study used data from a Texas Medicaid population to examine the schizophrenia-related costs and total healthcare costs for patients who received olanzapine versus risperidone. Multivariate analysis revealed no significant differences in schizophrenia-related costs for patients receiving olanzapine compared with risperidone, although total medical costs were significantly lower for patients initiated on olanzapine.

Dealing with skewed data: an example using asthma-related costs of medicaid clients

Side effects of some antidepressants include anxiety and insomnia. A retrospective drug utilization review was conducted to determine the amount of concurrent use of an antidepressant with medication that may counteract these side effects. Texas Medicaid claims data for 1993 included more than 30,000 patients receiving a specific serotonin reuptake inhibitor (SSRI) or clomipramine. A total of 35.0% of these patients were also taking a medication that could be used to relieve anxiety or induce sleep, and 15.2% of the total were receiving once-daily dosing of the latter type of medication. Concomitant use of SSRIs or clomipramine with trazodone occurred in 7.7% of the patients.

Evaluation of Health Care Costs and Utilization Patterns for Patients With Gout

The US Department of Defense recently assembled electronic records of outpatient prescriptions dispensed through the Uniformed Services Prescription Database Project (USPDP) going back to 1990. The objectives of this portion of a larger study were: (1) to examine longitudinally the patterns of antihypertensive drug use during the first year of therapy in patients whose initial therapy was with an angiotensin-converting enzyme (ACE) inhibitor or a calcium channel blocker (CCB); (2) to determine continuous and noncontinuous users of antihypertensive drugs; and (3) to estimate the direct medication costs for each pattern of medication use. Filtering criteria for patient and prescription identification were developed, because the USPDP contains no records of confirmatory diagnoses of hypertension. Once data filters were implemented, information for 771 patients was analyzed. An ACE inhibitor was the initial therapy for 328 patients, accounting for 1935 antihypertensive medication prescription fills, and a CCB was the initial therapy for 443 patients, accounting for 2459 fills (including refills). Slightly more than half of the patients (n = 401, 52.0%) were classified as continuous users (> or = 80% medication-possession ratio [supply of medication in days divided by the number of days in the 12-month study period]). In the first year, 177 of these continuous users (44.1%) had no change in therapy in the first year, 49 (12.2%) had an increase in dose, 8 (2.0%) had a decrease in dose, 15 (3.7%) had a change to a different therapeutic class of antihypertensive medication, 14 (3.5%) were changed to a different medication in the same therapeutic class, 20 (5.0%) had a new medication added to the regimen, and 118 (29.4%) had complex regimens involving more than one change. For continuous users, the mean medication supply in days was 354.6, and the average time before a medication change was 152.1 days for those continuous users who had one change in therapy. The overall average wholesale price (AWP) and average manufacturer price (AMP) for continuous users during 1 year of therapy were

Evaluation of Physician Intervention Letters

471.31 and