Sulfonylureas and Metformin Were Not Associated With an Increased Rate of Serious Bleeding in Warfarin Users: A Self-Controlled Case Series Study.
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SUBMITTER: Nam YH
PROVIDER: S-EPMC7788336 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prior research suggests that warfarin, when given concomitantly with some sulfonylureas, may increase the risk of serious hypoglycemia. However, the clinical significance remains unclear. We examined rate ratios (RRs) for the association between serious hypoglycemia and concomitant use of warfarin with either sulfonylureas or metformin using a self-controlled case series design and US Medicaid claims (supplemented with Medicare claims) from 1999 to 2011. Across all risk windows combined, warfarin was associated with an elevated rate of serious hypoglycemia when given concomitantly with glimepiride (RR, 1.47; 95% confidence interval (CI), 1.07-2.02) and metformin (RR, 1.73; 95% CI, 1.38-2.16). Particularly in the late risk window (>120 days since beginning concomitancy), most of the RRs for warfarin were elevated: glipizide (RR, 1.72; 95% CI, 1.29-2.29), glyburide (RR, 1.57; 95% CI, 1.15-2.15), metformin (RR, 2.26; 95% CI, 1.67-3.05), and glimepiride (RR, 1.56; 95% CI, 0.97-2.50). These results are consistent with a previously hypothesized hypoglycemic effect of warfarin in patients with type 2 diabetes through inhibition of the carboxylation of osteocalcin.
| S-EPMC6754096 | biostudies-literature
Project description:Study questionIs warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride?MethodsThis was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465,918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4,355,418 person quarters); 71,895 (15.4%) patients also filled a prescription for warfarin (416,479 person quarters with warfarin use). The main outcome measure was emergency department visit or hospital admission with a primary diagnosis of hypoglycemia in person quarters with concurrent fills of warfarin and glipizide/glimepiride compared with the rates in quarters with glipizide/glimepiride fills only, Multivariable logistic regression was used to adjust for individual characteristics. Secondary outcomes included fall related fracture and altered consciousness/mental status.Summary answer and limitationsIn quarters with glipizide/glimepiride use, hospital admissions or emergency department visits for hypoglycemia were more common in person quarters with concurrent warfarin use compared with quarters without warfarin use (294/416,479 v 1903/3,938,939; adjusted odds ratio 1.22, 95% confidence interval 1.05 to 1.42). The risk of hypoglycemia associated with concurrent use was higher among people using warfarin for the first time, as well as in those aged 65-74 years. Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visit for fall related fractures (3919/416,479 v 20,759/3,938,939; adjusted odds ratio 1.47, 1.41 to 1.54) and altered consciousness/mental status (2490/416,479 v 14,414/3,938,939; adjusted odds ratio 1.22, 1.16 to 1.29). Unmeasured factors could be correlated with both warfarin use and serious hypoglycemic events, leading to confounding. The findings may not generalize beyond the elderly Medicare population.What this study addsA substantial positive association was seen between use of warfarin with glipizide/glimepiride and hospital admission/emergency department visits for hypoglycemia and related diagnoses, particularly in patients starting warfarin. The findings suggest the possibility of a significant drug interaction between these medications.Funding, competing interests, data sharingJAR and DPG receive support from the National Institute on Aging, the Commonwealth Fund, and the Leonard D. Schaeffer Center for Health Policy and Economics at the University of Southern California. ABJ receives support from the NIH Office of the Director. No additional data are available.
| S-EPMC4670968 | biostudies-literature
Project description:This article aims to evaluate the real world risk of gastrointestinal bleeding among users naïve to dabigatran. We adopted a self-controlled case series design. We sampled 1215 eligible adult participants who were continuous insured users between July 1, 2010 and March 31, 2012 with use of dabigatran and at least one gastrointestinal bleeding episode. We used a conditional Poisson regression to estimate incidence rate ratios. The population consisted of 64.69% of male and 60.25% patients equal to or greater than age 65 at start of observation. After adjustment for time-variant confounders, the incidence rate of gastrointestinal bleeding was similar during dabigatran risk period and non-exposed period (incidence rate ratio [IRR]?=?1.01, 95% confidence interval [CI] 0.90, 1.15). There was no significant difference in GI incidence rate between periods of dabigatran and warfarin (IRR?=?0.99, 95% CI 0.75-1.31). Among this database of young and healthy participants, dabigatran was not associated with increased incidence rate of GI bleeding compared with non-exposed period among naïve dabigatran users. We did not detect an increased risk of GI bleeding over dabigatran vs warfarin risk period. Along with other studies on safety and effectiveness, this study should help clinicians choose the appropriate anticoagulant for their patients.
| S-EPMC5247708 | biostudies-other
Project description:ObjectiveTo estimate the association between untreated, community acquired, respiratory tract infections and bleeding in oral anticoagulant users.DesignSelf-controlled case series.SettingGeneral practices in England contributing data to the Clinical Practice Research Datalink GOLD.Participants1208 adult users of warfarin or direct oral anticoagulants with a general practice or hospital admission record of a bleeding event between January 2010 and December 2019, and a general practice record of a consultation for a community acquired respiratory tract infection for which immediate antibiotics were not prescribed (that is, untreated).Main outcome measuresRelative incidence of major bleeding and clinically relevant non-major bleeding in the 0-14 days after an untreated respiratory tract infection, compared to unexposed time periods.ResultsOf 1208 study participants, 58% (n=701) were male, median age at time of first bleed was 79 years (interquartile range 72-85), with a median observation period of 2.4 years (interquartile range 1.3-3.8). 292 major bleeds occurred during unexposed time periods and 41 in the 0-14 days after consultation for a respiratory tract infection. 1003 clinically relevant non-major bleeds occurred during unexposed time periods and 81 in the 0-14 days after consultation for a respiratory tract infection. After adjustment for age, season, and calendar year, the relative incidence of major bleeding (incidence rate ratio 2.68, 95% confidence interval 1.83 to 3.93) and clinically relevant non-major bleeding (2.32, 1.82 to 2.94) increased in the 0-14 days after an untreated respiratory tract infection. Findings were robust to several sensitivity analyses and did not differ by sex or type of oral anticoagulant.ConclusionsThis study observed a greater than twofold increase in the risk of bleeding during the 0-14 days after an untreated respiratory tract infection. These findings have potential implications for how patients and clinicians manage oral anticoagulant use during an acute intercurrent illness and warrant further investigation into the potential risks and how they might be mitigated.
| S-EPMC8689396 | biostudies-literature
Project description:BACKGROUND:Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. METHODS:The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use. RESULTS:Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. CONCLUSIONS:Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.
| S-EPMC5203951 | biostudies-literature
Project description: Not available
| S-EPMC7708459 | biostudies-literature
Project description:The objective of this study was to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all-cause mortality vs other commonly used antibiotics. We conducted a self-controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on diagnosis codes from emergency department visits and hospitalizations within Veterans Health Administration, and death in FY2014-FY2018. These Veterans also received outpatient prescriptions for FQs. Conditional Poisson regression models were used to estimate the association between FQs and each of the outcomes vs antibiotics of interest (ie amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole-trimethoprim), adjusted for time-varying covariates. Using a 30-day risk period after each antibiotic prescription, adjusted incidence rate ratios (aIRRs) for FQs vs each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, incidence was higher during FQ risk periods vs amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods. A significantly increased risk of mortality was observed with FQs vs each antibiotic of interest. FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all-cause mortality vs multiple antibiotics commonly used for outpatient infections. Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.
| S-EPMC7550792 | biostudies-literature
Project description:IntroductionNew target-specific oral anticoagulants may have benefits, such as shorter hospital length of stay, compared to warfarin in patients with nonvalvular atrial fibrillation (NVAF). This study aimed to assess, among patients with NVAF, the effect of rivaroxaban versus warfarin on health care costs in a cohort of rivaroxaban users and matched warfarin users.MethodsHealth care claims from the Humana database from 5/2011 to 12/2012 were analyzed. Adult patients newly initiated on rivaroxaban or warfarin with ≥2 atrial fibrillation (AF) diagnoses (The International Classification of Diseases, Ninth Revision, Clinical Modification: 427.31) and without valvular AF were identified. Based on propensity score methods, warfarin patients were matched 1:1 to rivaroxaban patients. Patients were observed up to end of data, end of insurance coverage, death, a switch to another anticoagulant, or treatment nonpersistence. Health care costs [hospitalization, emergency room (ER), outpatient, and pharmacy costs] were evaluated using Lin's method.ResultsMatches were found for all rivaroxaban patients, and characteristics of the matched groups (n = 2253 per group) were well balanced. Estimated mean all-cause and AF-related hospitalization costs were significantly lower for rivaroxaban versus warfarin patients (all-cause: $5411 vs. $7427, P = 0.047; AF-related: $2872 vs. $4147, P = 0.020). Corresponding estimated mean all-cause outpatient visit costs were also significantly lower, but estimated mean pharmacy costs were significantly higher for rivaroxaban patients ($5316 vs. $2620, P < 0.001). Although estimated mean costs of ER visits were higher for rivaroxaban users compared to those of warfarin users, differences were not statistically significant. Including anticoagulant costs, mean overall total all-cause costs were comparable for rivaroxaban versus warfarin users due to cost offset from a reduction in the number and length of hospitalizations and number of outpatient visits ($17,590 vs. $18,676, P = 0.542).ConclusionDespite higher anticoagulant cost, mean overall total all-cause and AF-related cost remains comparable for patients with NVAF treated with rivaroxaban versus warfarin due to the cost offset from reduced health care resource utilization.
| S-EPMC4376962 | biostudies-literature
Project description:AIM:To determine whether genetic variants associated with warfarin dose variability were associated with increased risk of major bleeding during warfarin therapy. MATERIALS & METHODS:Using Vanderbilt's DNA biobank we compared the prevalence of CYP2C9, VKORC1 and CYP4F2 variants in 250 cases with major bleeding and 259 controls during warfarin therapy. RESULTS:CYP2C9*3 was the only allele that differed significantly among cases (14.2%) and controls (7.8%; p = 0.022). In the 214 (85.6%) cases with a major bleed 30 or more days after warfarin initiation, CYP2C9*3 was the only variant associated with bleeding (adjusted odds ratio: 2.05; 95% CI: 1.04, 4.04). CONCLUSION:The CYP2C9*3 allele may double the risk of major bleeding among patients taking warfarin for 30 or more days.
| S-EPMC4304738 | biostudies-literature
Project description:To determine if incident oral antidiabetic drug (OAD) use was associated with 12-month systolic blood pressure (BP) and if this was mediated through body mass index (BMI) changes.A retrospective cohort of veterans with hypertension who initiated metformin (n = 2057) or sulfonylurea (n = 1494) between 1 January 2000 and 31 December 2007 in the Veterans Administration Mid-South Network was assembled. Patients were included if they had complete covariates, including 12-month BP and BMI, and persisted on therapy for 12 months. Linear regression was conducted to investigate the effect of OADs on 12-month systolic BP adjusting for demographics, glycated hemoglobin, creatinine, BMI, health care utilization, and comorbidities, including cardiovascular disease (CVD). A second analysis examined if these effects were mediated by BMI change. The secondary outcome was the proportion of patients who had a controlled BP (? 140/90 mmHg) at 12 months adjusted for baseline BP and covariates.Patients were white (82%) males (97%) with median age of 64 years (interquartile range [IQR] 57, 72), and 27% had history of CVD. Sulfonylurea users had a 1.33 mmHg (0.16, 2.50, p = 0.03) higher 12-month systolic BP than metformin users. The median change in BMI from OAD initiation to 12 months was -0.76 (IQR -1.78, 0.07) and 0.21 (IQR -0.57, 1.03) among metformin and sulfonylurea users, respectively. In a model adjusting for BMI change, the difference in 12-month systolic BP between sulfonylurea and metformin users became insignificant (0.23 (-1.00, 1.45), p = 0.72), while one BMI unit change was associated with an increase in 12-month systolic BP of 1.07 mmHg (0.74, 1.40, p < 0.0001). At 12 months, 68.3% of metformin patients had controlled BP versus 64.2% of sulfonylurea patients (p = 0.01).Compared with metformin, sulfonylurea initiation was associated with increased systolic BP at 12 months, which appears to be mediated by the differential effects of these drugs on BMI.
| S-EPMC4667555 | biostudies-literature