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Brian F Gage

Publications and source records attributed to Brian F Gage.

35 records · Page 2Linked to original sources
PubMed2004

Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin.

BACKGROUND: The rate of stroke in atrial fibrillation (AF) depends on the presence of comorbid conditions and the use of antithrombotic therapy. Although adjusted-dose warfarin is superior to aspirin for reducing stroke in AF, the absolute risk reduction of warfarin depends on the stroke rate with aspirin. This prospective cohort study tested the predictive accuracy of 5 stroke risk stratification schemes. METHODS AND RESULTS: The study pooled individual data from 2580 participants with nonvalvular AF who were prescribed aspirin in a multicenter trial (Atrial Fibrillation, Aspirin, Anticoagulation I study [AFASAK-1], AFASAK-2, European Atrial Fibrillation Trial, Primary Prevention of Arterial Thromboembolism in patients with nonrheumatic Atrial Fibrillation in primary care study, and Stroke Prevention and Atrial Fibrillation [SPAF]-III high risk or SPAF-III low risk). There were 207 ischemic strokes during 4887 patient-years of aspirin therapy. All schemes predicted stroke better than chance, but the number of patients categorized as low and high risk varied substantially. AF patients with prior cerebral ischemia were classified as high risk by all 5 schemes and had 10.8 strokes per 100 patient-years. The CHADS(2) scheme (an acronym for Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack) successfully identified primary prevention patients who were at high risk of stroke (5.3 strokes per 100 patient-years). In contrast, patients identified as high risk by other schemes had 3.0 to 4.2 strokes per 100 patient-years. Low-risk patients identified by all schemes had 0.5 to 1.4 strokes per 100 patient-years of therapy. CONCLUSIONS: Patients with AF who have high and low rates of stroke when given aspirin can be reliably identified, allowing selection of antithrombotic prophylaxis to be individualized.

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PubMed2004

Effect of warfarin nonadherence on control of the International Normalized Ratio.

OBJECTIVE: The frequency and causes of ab- errant International Normalized Ratios (INRs) in warfarin recipients and the percentage explainable by warfarin nonadherence were studied. METHODS: The medical records of patients whose warfarin therapy was monitored by a telephone-based anticoagulation service in a Midwestern urban hospital between March 2000 and March 2001 were reviewed for causes of out-of-range INRs, the percentage of out-of-range INRs attributable to warfarin nonadherence, and demographic and clinical variables predictive of nonadherence. RESULTS: Data from 347 patients were studied. The cohort yielded 4305 INRs, of which 1002 (23%) were out of range (lower than 1.8 or higher than 3.4). Thirty-six percent of the out-of-range INRs were due to warfarin or dietary nonadherence, 9% were due to medical systems problems (including drug interactions), 18% were due to a change in clinical status, and 38% were idiopathic. Age younger than 65 years, age greater than 80 years, and living closer to the laboratory were predictive of warfarin nonadherence. CONCLUSION: Warfarin nonadherence was the most common cause of explainable aberrant INRs in patients taking warfarin. Age younger than 65 years, age greater than 80 years, and living close to the laboratory were predictive of warfarin nonadherence.

Age Factors↗
PubMed2004

The management of anticoagulants in the periendoscopic period for patients with atrial fibrillation: a decision analysis.

PURPOSE: The management of patients who undergo endoscopy while being treated with warfarin is challenging. We used decision analysis to determine the preferred strategy to manage anticoagulants in the periendoscopic period. METHODS: We designed a Markov model to estimate costs and quality-adjusted survival during a 10-year period in patients with nonvalvular atrial fibrillation undergoing screening colonoscopy. We compared six alternatives to the continue-warfarin strategy, which was to perform colonoscopy while the patient was taking full-dose warfarin. The hold-warfarin strategy was to stop warfarin 5 days before the colonoscopy. The repeat endoscopy strategy was to continue warfarin for a diagnostic colonoscopy, followed by a repeat procedure after cessation of warfarin if polypectomy was required. The dose-reduction strategy was to reduce the warfarin dose before colonoscopy. The low molecular weight heparin strategy was to administer subcutaneous low molecular weight heparin for 2 days before and 2 days after colonoscopy. The unfractionated heparin strategy was to administer intravenous unfractionated heparin for 2 days before and 2 days after the procedure. The vitamin K strategy was to hold warfarin for 4 days and to administer vitamin K if the international normalized ratio (INR) exceeded 2.0 the day before the procedure, or low molecular weight heparin if the INR was less than 1.5. RESULTS: For screening colonoscopy, assuming that polyps would be removed in 35% of examinations, the hold-warfarin and dose-reduction arms were both cost-effective strategies. The hold-warfarin arm was most cost-effective if the likelihood of polypectomy exceeded 60%, or if there was a low risk of stroke despite atrial fibrillation. The continue-warfarin strategy was preferred if the probability of polypectomy was 1% or less. CONCLUSION: Temporary warfarin cessation or halving the warfarin dose for several days before endoscopy was the preferred strategy for most patients. Periendoscopic heparin therapy was not cost-effective for patients with nonvalvular atrial fibrillation.

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PubMed2004

Yield of surveillance bronchoscopy for acute rejection and lymphocytic bronchitis/bronchiolitis after lung transplantation.

BACKGROUND: Better understanding of the timing and pattern of surveillance bronchoscopy findings after lung transplantation could influence the timing and frequency of surveillance bronchoscopy. We present our surveillance bronchoscopy experience and test the hypothesis that patients not encountering early acute rejection or lymphocytic bronchitis/bronchiolitis are less likely to have subsequent occult occurrences in the 1st year after lung transplantation. METHODS: We conducted a retrospective study of 204 patients who underword transplantation between 1996 and 2000. Based on contemporary biopsy-specimen grading in the first 100 days, we formed 2 groups: No Early Rejection and Early Rejection. We compared subsequent yields of surveillance bronchoscopy and the incidence of acute rejection or of lymphocytic bronchitis/bronchiolitis. RESULTS: We reviewed 645 biopsies taken from 204 recipients during the first 100 days to classify patients into a No Early Rejection Group (n=67) or an Early Rejection Group (n=137). Yield of surveillance bronchoscopy for acute rejection or lymphocytic bronchitis/bronchiolitis was 31% with the greatest yield during the first 30 days (45%), and then decreasing to 26% (p <0.001). After Day 100, 71% of occult acute rejection episodes involved minimal (A1) lesions. Yield of surveillance bronchoscopy after Day 100 was 20% in the No Early Rejection Group and was 27% in the Early Rejection Group (p=0.22). Incidence of acute rejection or lymphocytic bronchitis/bronchiolitis after Day 100 was 41% in the No Early Rejection Group and was 50% in the Early Rejection Group (p=0.17). CONCLUSION: Surveillance bronchoscopy detects occult acute rejection or lymphocytic bronchitis/bronchiolitis in approximately one-third of biopsy specimens during the 1st year, with the majority of late abnormalities being minimal (A1) rejection. The absence of acute rejection or lymphocytic bronchitis/bronchiolitis during the first 100 days does not predict freedom from such events in the remainder of the 1st year.

Acute Disease↗
PubMed2004

Cost-effectiveness of extending Medicare coverage of immunosuppressive medications to the life of a kidney transplant.

Unless they maintain Medicare status through disability or age, kidney transplant recipients lose their Medicare coverage of immunosuppression 3 years after transplantation. A significant transplant survival advantage has previously been demonstrated by the extension of Medicare immunosuppressive medication coverage from 1 year to 3 years, which occurred between 1993 and 1995. The United States Renal Data System (USRDS) was analyzed for recipients of kidney transplants from 1995 to 1999. Using a Markov model, we estimated survival and costs of the current system of 3-year coverage compared with lifetime immunosuppression coverage. Results were calculated from the perspectives of society and Medicare. Extension of immunosuppression coverage produced an expected improvement from 38.6% to 47.6% in graft survival and from 55.4% to 61.8% in patient survival. The annualized expected savings to society from lifetime coverage was $136 million assuming current rates of transplantation. Medicare would break-even compared with current coverage if the fraction of patients using extended coverage was <32%. The extension would be cost-effective to Medicare if this fraction was <91%. Extended Medicare immunosuppression coverage to the life of a kidney transplant should result in better transplant and economic outcomes, and should be considered by policy makers.

Cost-Benefit Analysis↗
PubMed2004

Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin.

Knowledge of pharmacogenetics may help clinicians predict their patients' therapeutic dose of warfarin, thereby decreasing the risk of bleeding during warfarin initiation. Our goal was to use pharmacogenetics to develop an algorithm that uses genetic, clinical, and demographic factors to estimate the warfarin dose a priori. We collected a blood sample, demographic variables, laboratory values, smoking status, names of medications, and dietary history from 369 patients who were taking a maintenance dose of warfarin. Using polymerase chain reaction, we genotyped each participant for the presence of 8 polymorphisms in the cytochrome P450 2C9 system. Using multiple regression, we quantified the association between warfarin dose and all factors. Advanced age, lower body surface area (BSA), and the presence of cytochrome P450 2C9 *2 or *3 single nucleotide polymorphisms were strongly associated (P < 0.001) with lower warfarin dose: the maintenance dose decreased by 8% per decade of age, by 13% per standard deviation decrease in BSA, by 19% per 2C9*2 allele, and by 30% per 2C9*3 allele. Warfarin doses were 29% lower in patients who took amiodarone, 12% lower in patients who took simvastatin, 21% lower in patients whose target INR was 2.5 rather than 3.0, and 11% lower in white rather than African-American participants (P < 0.05 for these comparisons). An algorithm that included these factors and one of borderline significance (sex), explained 39% of the variance in the maintenance warfarin dose. Use of this pharmacogenetic model had potential to prevent patients from being overdosed when initiating warfarin: we estimate that only 24 (6.5%) patients would have been over- dosed by >2 mg/day with pharmacogenetic dosing compared to 59 (16%) patients who would have been overdosed if they had been prescribed the empirical dose of 5 mg/day (P < 0.001). In conclusion, the maintenance warfarin dose can be estimated from demographic, clinical, and pharmacogenetic factors that can be obtained at the time of warfarin initiation.

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PubMed2004

Use of pharmacogenetics to guide warfarin therapy.

The Human Genome Project heralds new opportunities for pharmacogenetics, the use of genetics to individualize the application of pharmaceuticals in the practice of medicine (1-3). Single nucleotide polymorphisms (SNPs) and other genetic variants in genes responsible for absorption, metabolism and excretion have been associated with alterations in drug disposition or effect. Warfarin is a potential target for pharmacogenetics-based dosing because of its wide use, variability in individual response, high prevalence of genetic variants and severity of adverse drug reactions (4). The genotype assays for genetic variants relevant to warfarin are widely used and are being developed for commercial use (5), making the promise of a pharmacogenetics-based approach a near reality.

Anticoagulants↗
PubMed2003

Predictors of mortality in younger and older patients with heart failure and preserved or reduced left ventricular ejection fraction.

BACKGROUND: Although half of elderly patients with heart failure have preserved left ventricular ejection fraction (LVEF), little is known about predictors of mortality in this group. METHODS: We reviewed the charts of 400 patients hospitalized at an academic medical center in 1999 with a principal discharge diagnosis of heart failure. Patients were divided into 4 groups on the basis of age > or =75 or <75 years and the presence of preserved or reduced LVEF. Vital status was ascertained as of October 2001. RESULTS: A total of 373 patients (mean age 69.1 years, 56.0% female, 47.5% nonwhite) underwent echocardiography to assess LVEF. Of these, 216 patients were <75 years of age (81 with preserved LVEF [group 1, 21.7%] and 135 with reduced LVEF [group 2, 36.2%]), and 157 were > or =75 years of age (81 with preserved LVEF [group 3, 21.7%] and 76 with reduced LVEF [group 4, 19.6%]). After a mean follow-up of 25 months, independent predictors of mortality among the 4 groups differed substantially: group 1, male sex, prescription of a calcium-channel blocker, and diuretic dose at discharge; group 2, blood urea nitrogen (BUN), lower hemoglobin level, and not being prescribed a beta-blocker at discharge; group 3, BUN; and group 4, older age, history of myocardial infarction, severity of reduced LVEF, and diuretic dose. CONCLUSION: In patients with heart failure, predictors of mortality vary by age and by the presence of preserved or reduced LVEF. Traditional predictors of mortality in patients with reduced LVEF may not apply to elderly patients with preserved LVEF.

Age Factors↗
PubMed2003

Outpatient treatment of acute venous thromboembolic disease.

Once- or twice-daily subcutaneous dosing of LMWHs without laboratory monitoring has facilitated outpatient VTE therapy. Clinical trials have demonstrated at least equivalent efficacy and safety and potential cost savings of outpatient therapy for uncomplicated proximal DVT with LMWH when compared with inpatient therapy. Explicit criteria exist for outpatient DVT therapy. Home therapy for PE requires further evaluation before it can be recommended outside of a trial or other supervised setting.

Acute Disease↗
PubMed2003

Warfarin dose reduction vs watchful waiting for mild elevations in the international normalized ratio.

BACKGROUND: Whether clinicians should decrease the warfarin dose in response to a mild, asymptomatic elevation in the international normalized ratio (INR) is unknown. OBJECTIVES: The study objectives were as follows: (1) to evaluate the safety of an anticoagulation service (ACS) policy advocating that the warfarin dose not be changed for isolated, asymptomatic INRs of < or = 3.4; (2) to compare the dosing strategies of an ACS and primary care providers (PCPs); and (3) to quantify the relationship between reduction of the warfarin dose and the subsequent fall in the INR. DESIGN AND SETTING: Randomized controlled study of health maintenance organization outpatients who were receiving warfarin. PATIENTS: We identified 231 patients with a target INR of 2.5 and an isolated, asymptomatic INR between 3.2 and 3.4. Our ACS monitored 103 of the patients; PCPs monitored the remaining 128 patients. MEASUREMENTS: From all 231 patients, we obtained INRs and warfarin dosing history. From the 103 ACS enrollees, we also recorded adverse events. RESULTS: One ACS patient had epistaxis in the 30 days after the elevated INR. Twenty-three percent of ACS enrollees and 47% of PCP patients reduced their warfarin dose (p < 0.001). The median follow-up INRs were similar in both cohorts: 2.7 in the ACS enrollees and 2.6 in the PCP patients. However, in a subgroup analysis of 190 patients who presented with an INR of 3.2 or 3.3, ACS enrollees were more likely to have a follow-up INR in the range of 2 to 3 (p = 0.03). The median follow-up INR was 2.7 in 148 patients who maintained their warfarin dose, 2.5 in 77 patients who decreased their dose by 1 to 20%, and 1.7 in 6 patients who decreased their dose by 21 to 43% (p < 0.001). CONCLUSIONS: These findings support maintaining the same warfarin dose in asymptomatic patients with an INR of < or = 3.3, and reducing the dose for patients who have a greater INR or an increased risk of hemorrhage. Warfarin dose reductions > 20% should be avoided for mildly elevated INRs.

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PubMed2002

Substitution of generic warfarin for Coumadin in an HMO setting.

BACKGROUND: Substitution of generic warfarin for Coumadin presents safety concerns due to warfarin's narrow therapeutic index and because a prior generic formulation was removed from the US market after it was associated with adverse events. OBJECTIVE: To determine whether a health maintenance organization (HMO) can add generic warfarin to its formulary without adversely affecting warfarin management or increasing adverse events. DESIGN: In a prospective, observational study, an HMO that formerly dispensed only Coumadin added a generic warfarin preparation (Barr Laboratories, Pomona, NY) to its formulary. SETTING: An anticoagulation service (ACS) affiliated with an HMO that was based in St. Louis, MO. PARTICIPANTS: The cohort consisted of 182 enrollees in the ACS as of May 1, 1999. At the start of the study, these participants were taking Coumadin; by October 31, 2000, all had switched to Barr warfarin. MEASUREMENTS AND MAIN RESULTS: We collected data 8 months prior to and 10 months after the introduction of generic warfarin for the following endpoints: international normalized ratio (INR) control, frequency of INR monitoring, number of dose changes, and rate of thrombotic and hemorrhagic events. Statistical process control charts were used to differentiate between random variation in the endpoints and changes due to different warfarin formulations, and we used the Wilcoxon signed-rank test to look for a change in any endpoint after patients changed to generic warfarin. No significant differences were found in any endpoint. CONCLUSIONS: Substitution of Barr warfarin for Coumadin did not significantly affect INR control, warfarin management, or adverse events. Our findings suggest that HMOs can safely substitute at least 1 generic formulation of warfarin without extra monitoring.

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PubMed2002

Risk factors for bleeding in patients taking coumarins.

Coumarins (e.g., warfarin) are used for the treatment and prophylaxis of venous and arterial thromboembolism. Unfortunately, their use is limited by bleeding. In deciding whether to initiate coumarin therapy, the therapeutic benefits must be weighed against the potential risk of bleeding for each individual patient. The major determinants of coumarin-related bleeding are the intensity of anticoagulant effect as measured by the International Normalized Ratio, patient characteristics, concomitant use of other drugs, and the length of anticoagulant therapy. At the initiation of coumarin therapy, the risk factors for bleeding can be identified by the COUMARINS acronym and by one of the bleeding prediction models. During ongoing therapy with coumarins, the risks and benefits of therapy should be reassessed periodically. This article reviews the current evidence for the prediction and prevention of coumarin-related bleeding.

Anticoagulants↗
PubMedDate not supplied

Pharmacogenetics and anticoagulant therapy.

Warfarin and other coumarins are metabolized by the cytochrome P450 2C9 complex. Common single-nucleotide polymorphisms (SNPs) in this enzyme are associated with an exaggerated elevation in the INR during warfarin initiation and an increased risk of bleeding. These observations suggest that patients known to carry the putative SNPs should be started on lower doses of warfarin therapy or have their INR values monitored more frequently during warfarin initiation. Such clinical variables as age, body surface area, and concomitant medications also play important roles in determining the maintenance dose of warfarin. Thus, a comprehensive dosing algorithm offers the most promising approach to estimating the therapeutic dose of warfarin a priori and to preventing hemorrhage during warfarin induction.

Anticoagulants↗
PubMedDate not supplied

Cost-savings analysis of using a portable coagulometer for monitoring homebound elderly patients taking warfarin.

The authors present a prospective cost-savings analysis to determine how the use of portable coagulometers in the home health setting affects medical expenditure. Thirty-five elderly patients (mean age 67 years) receiving cardiac home health care and long-term oral anticoagulation were evaluated with paired measurements of the international normalized ratio by both a traditional, laboratory-based prothrombin time and a point-of-care coagulometer (CoaguChek, Roche Diagnostics, Basel, Switzerland). Costs for materials, procedures, transportation, and labor were summed for both methods, and it was found that cost of international normalized ratio determination by the portable coagulometer was significantly less than the traditional method ($6.85 vs. $17.30; p<0.001). The authors conclude that by saving on the costs of transporting and processing traditional international normalized ratio specimens, use of point-of-care coagulometers by home health nurses could reduce medical expenditure. The cost savings and potential improvement in quality of care argue for equipping home health nurses with portable coagulometers.

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PubMedDate not supplied

Preference-based antithrombotic therapy in atrial fibrillation: implications for clinical decision making.

BACKGROUND: Patient preferences and expert-generated clinical practice guidelines regarding treatment decisions may not be identical. The authors compared the thresholds for antithrombotic treatment from studies that determined or modeled the treatment preferences of patients with atrial fibrillation with recommendations from clinical practice guidelines. METHODS: Methods included MEDLINE identification, systematic review, and pooling with some reanalysis of primary data from relevant studies. RESULTS: Eight pertinent studies, including 890 patients, were identified. These studies used 3 methods (decision analysis, probability tradeoff, and decision aids) to determine or model patient preferences. All methods highlighted that the threshold above which warfarin was preferred over aspirin was highly variable. In 6 of 8 studies, patient preferences indicated that fewer patients would take warfarin compared to the recommendations of the guidelines. In general, at a stroke rate of 1% with aspirin, half of the participants would prefer warfarin, and at a rate of 2% with aspirin, two thirds would prefer warfarin. In 3 studies, warfarin must provide at least a 0.9% to 3.0% per year absolute reduction in stroke risk for patients to be willing to take it, corresponding to a stroke rate of 2% to 6% on aspirin. CONCLUSIONS: For patients with atrial fibrillation, treatment recommendations from clinical practice guidelines often differ from patient preferences, with substantial heterogeneity in their individual preferences. Since patient preferences can have a substantial impact on the clinical decision-making process, acknowledgment of their importance should be incorporated into clinical practice guidelines. Practicing physicians need to balance the patient preferences with the treatment recommendations from clinical practice guidelines.

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