RESUMO
BACKGROUND: The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. METHODS: We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy. RESULTS: At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy. CONCLUSIONS: Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).
Assuntos
Algoritmos , Anticoagulantes/administração & dosagem , Hidrocarboneto de Aril Hidroxilases/genética , Genótipo , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Adulto , Idoso , Anticoagulantes/efeitos adversos , Citocromo P-450 CYP2C9 , Método Duplo-Cego , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Masculino , Farmacogenética , Tromboembolia , Falha de Tratamento , Varfarina/efeitos adversosRESUMO
Warfarin is an anticoagulant medication that is challenging to manage. Dabigatran has been approved by the FDA for stroke and systemic embolism prevention in non-valvular atrial fibrillation as an alternative to warfarin. Dabigatran does not require routine monitoring, has an established dose, and lacks many of the drug, herbal, and food interactions that afflict warfarin. To evaluate patients' satisfaction with their current warfarin treatment and their opinion on switching to a newly marketed medication (dabigatran) through a brief survey. Two separate surveys were administered to (1) evaluate the patients' opinion of their warfarin therapy and (2) evaluate their thoughts on switching to a newer anticoagulant. Responses were recorded on a rating scale of 1-5; 1 being the least and 5 being the highest. Study was conducted at the Georgia Regents Health System (GRHS) pharmacy-based anticoagulation clinic. Two hundred sixty patients on warfarin treatment were enrolled. Patients expressed high satisfaction with warfarin treatment (4.7 ± 0.78). However, a vast majority of the patients were willing to switch to an agent that: requires less frequent follow-up visits (3.9 ± 1.35); lacks interaction with food and/or beverage (4.1 ± 1.25); is as efficacious as warfarin (3.7 ± 1.38). Patients expressed that out-of-pocket cost would be a major barrier to switch to this new medication (1.3 ± 0.58). Patients are satisfied with their warfarin treatment but willing to consider a new anticoagulant. Cost was highlighted as the most significant barrier. Efficacy, dietary freedom and less frequent visits are the major factors affecting the patients' decision.
Assuntos
Anticoagulantes/administração & dosagem , Benzimidazóis/administração & dosagem , Substituição de Medicamentos , Adesão à Medicação , Satisfação do Paciente , Varfarina/administração & dosagem , beta-Alanina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/economia , Benzimidazóis/efeitos adversos , Benzimidazóis/economia , Custos e Análise de Custo , Dabigatrana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Varfarina/efeitos adversos , Varfarina/economia , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversos , beta-Alanina/economiaRESUMO
Time in therapeutic range (TTR), a well-recognized performance metric of oral anticoagulation, measures the time when patients' international normalized ratios (INRs) are within the desired range. The TTR value can vary significantly depending on the type of method used and can be a skewed indicator of the overall quality of anticoagulation. As such, the present study was designed to compare three methods for TTR calculation (cross-sectional, traditional, and Rosendaal) to quantify their differences, biases, and trends. As part of this investigation, a 21-week retrospective analysis of patients on warfarin was conducted to compare TTR values obtained by these three methods. Paired t-tests, correlation studies between size and bias, and Bland-Altman plots were performed using SAS 9.4 (SAS Institute, Cary, NC, USA). It was revealed that the TTR values for the cross-sectional, Rosendaal, and traditional methods were 65.97, 58.12, and 51.55, respectively. The addition of tolerances to INR ranges of ± 0.2 and ± 0.5 increased TTR values to 81.79 and 91.53, respectively, for the cross-sectional method, and 66.86 and 82.69, respectively, for the traditional method. The use of the traditional method resulted in significantly higher TTR values than did use of the Rosendaal method, with high variability between the methods in both positive and negative directions. There was a demonstrated lack of independence between the methods, and zero bias could not be assumed. In conclusion, the different methods considered in the present study do not accurately measure whether a patient is in or out of the therapeutic range, and the addition of tolerances can further distort the perception of anticoagulation achieved. We recommend a standardized TTR calculation method as well as a uniform tolerance for use in clinical trials and quality control efforts.
RESUMO
Isolated systolic hypertension is the most common form of hypertension, especially among patients 50 years or older. What is not appreciated is that there are secondary causes of isolated systolic hypertension. Hyperthyroidism increases systolic blood pressure by decreasing systemic vascular resistance, increasing heart rate, and raising cardiac output. Potential cardiovascular consequences of hyperthyroidism include atrial arrhythmias (especially atrial fibrillation), pulmonary hypertension, left ventricular hypertrophy, and heart failure. The prevalence of hypertension is greater among hyperthyroid patients than euthyroid patients. Whether there is a blunted nocturnal decline in ambulatory blood pressure among hyperthyroid patients is more controversial. Treatment is associated with a reduction in systolic blood pressure, heart rate, and cardiac output.
Assuntos
Hipertensão/etiologia , Hipertireoidismo/complicações , Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/fisiopatologia , Fatores de RiscoAssuntos
Benzimidazóis/efeitos adversos , Coeficiente Internacional Normatizado , Sistemas Automatizados de Assistência Junto ao Leito , Trombina/antagonistas & inibidores , beta-Alanina/análogos & derivados , Idoso , Benzimidazóis/uso terapêutico , Dabigatrana , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêuticoRESUMO
A 32-year-old black female was started on phenytoin for seizure prophylaxis following the clipping of an aneurysm. This was stopped after 3 weeks when she developed a generalized skin rash. Over the next week she developed fever, sore throat, dysphagia, and headache. She had an erythematous throat with white exudates on the right tonsil and 1 to 3 cm firm, tender lymphadenopathy in multiple regions. Blood, throat swab and cerebrospinal fluid studies were negative for bacterial or viral infections, except for elevated liver enzymes. CT scan of chest, abdomen, and pelvis showed no lymphadenopathy. Lymph node biopsy suggested necrosis but no evidence of infection, granuloma, or lymphoma. Her lymphadenopathy resolved spontaneously and liver enzymes normalized in 3 weeks. Hypersensitivity syndrome due to antiepileptics manifests as fever, rash, generalized lymphadenopathy, and probably represents a T-cell mediated drug reaction. This reaction may persist despite cessation of the drug, and it may engender expensive evaluation. Careful observation up to 3 weeks after drug cessation may be the best management.
Assuntos
Anticonvulsivantes/efeitos adversos , Hipersensibilidade a Drogas/complicações , Hipersensibilidade a Drogas/etiologia , Linfonodos/patologia , Linfadenite/complicações , Fenitoína/efeitos adversos , Adulto , Feminino , Humanos , Necrose/complicaçõesRESUMO
Sarcoidosis is a granulomatous, multisystem disease. Rarely, sarcoidosis may present with both renal failure and hypercalcemia. A 27-year-old black man presented with severe abdominal pain and renal failure. A kidney biopsy demonstrated features of both interstitial nephritis and membranous glomerulopathy thought to be secondary to nonsteroidal anti-inflammatory drugs. His renal function and symptoms improved with short-term prednisone therapy. Discontinuation of steroids led to a recurrence of renal failure and severe hypercalcemia. On the basis of an elevated angiotensin-converting enzyme level of 160 U/L and anemia, a bone marrow biopsy was performed. Acid-fast bacillus-negative, noncaseating granulomas suggested the diagnosis of sarcoidosis. The patient recovered after restarting prednisone. Sarcoidosis may cause both interstitial and membranous nephritis from direct infiltration. Hypercalcemia results from increased calcium absorption secondary to 1,25-dihydroxyvitamin D production by sarcoid granulomas. Sarcoidosis must be considered in the differential diagnosis of renal failure in black patients. Serum calcium and angiotensin-converting enzyme levels may aid the diagnosis.