warfarin and Pulmonary-Disease--Chronic-Obstructive

To administer optimal and safe pharmacotherapy, development of stratified and personalized therapy is imperative. Pharmacogenomics (PGx) is useful in elucidating factors causing individual differences in drug efficacy and the emergence of adverse effects. It also helps design accurate drug administration methods by evaluating the effects of patient-related factors, such as genetic factors, that influence pharmacokinetics (PK) and pharmacodynamics (PD). In addition, selection of appropriate therapeutic agents requires the implementation of precision medicine allowing accurate disease diagnosis. To establish precision medicine, it is necessary to uncover the association of pathophysiological factors, which are represented as endotype or genotype, with the pathology of several phenotypes. This review describes two aspects related to realization of individualized medicine, namely the effectiveness of PK/PD/PGx studies and the stratification of pathological conditions. First, we conducted a PK/PD/PGx study with the aim to individualize warfarin treatment. In this study, we elucidated the effect of CYP4F2 polymorphisms associated with vitamin K metabolism by measuring the blood concentrations of warfarin and vitamin K. Then, to develop precision medicine for asthma and chronic obstructive pulmonary disease (COPD), we analyzed not only clinical symptoms but also pathological biomarkers and genes associated with inflammation. The findings may contribute toward better understanding of the pathological conditions of asthma, COPD, and asthma-COPD overlap.

Topics: Asthma; Cytochrome P450 Family 4; Drug Therapy; Humans; Inflammation; Pharmacogenomic Testing; Pharmacokinetics; Polymorphism, Genetic; Precision Medicine; Pulmonary Disease, Chronic Obstructive; Vitamin K; Warfarin

To report a case of bilateral spontaneous hyphaema in a patient on warfarin sodium for atrial fibrillation and COPD. A case report and literature review. A 76-year-old man presented with bilateral spontaneous hyphaema. There was no anterior chamber pathology known to predispose for spontaneous bleeding except for a history of paroxysmal atrial fibrillation treated with a daily dose of 3 mg of warfarin sodium. In addition, he was also suffering from severe COPD and was on oxygen supplementation. This is a rare case of a bilateral spontaneous hyphaema. Although the patient was on warfarin sodium, his INR was only 2.6 at the onset of his symptoms. It may be possible that the combined action of anti-coagulant properties of warfarin sodium and hypoxic vasodilatation of iris vessels may be responsible for bilateral hyphaema in this case.

Topics: Aged; Humans; Hyphema; Hypoxia; Iris; Male; Pulmonary Disease, Chronic Obstructive; Vasodilation; Warfarin

Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood.. We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors.. COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p=0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p<0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p=0.617).. COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Warfarin

Topics: Accidental Falls; Aged; Anticoagulants; Atrial Fibrillation; Buttocks; Deprescriptions; Embolization, Therapeutic; Enoxaparin; Hematoma; Hemoptysis; Humans; International Normalized Ratio; Male; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Warfarin

 Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes..  This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of patients taking warfarin..  A cohort of warfarin users aged 18 to 85 years from January 2005 to April 2013 was identified in The Health Improvement Network U.K. primary care database (.  Among the factors examined, the strongest predictors of over-anticoagulation were warfarin indication (in particular, valvular atrial fibrillation and valve replacement), renal failure (with the risk increasing steeply with decreasing estimated glomerular filtration rate), cancer, anaemia, respiratory infections treated with antibiotics, chronic obstructive pulmonary disease treated with β2-agonists, polypharmacy (≥10 medications), low socio-economic status and residency in rural areas. Similar results were obtained when supratherapeutic levels were defined as INR ≥5 or, alternatively, as INR > 3..  Predictors of supratherapeutic INR levels found in this study might help physicians identify patients where closer INR monitoring is warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Anticoagulants; Blood Coagulation; Case-Control Studies; Databases, Factual; Female; Glomerular Filtration Rate; Humans; International Normalized Ratio; Male; Medical Overuse; Middle Aged; Neoplasms; Odds Ratio; Poverty; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Regression Analysis; Renal Insufficiency; Respiratory Tract Infections; Rural Population; United Kingdom; Warfarin; Young Adult

Heart failure (HF) has been associated with an elevated international normalized ratio (INR) in patients on warfarin.. Compare warfarin sensitivity during hospital admission for HF exacerbation and chronic obstructive pulmonary disease (COPD) exacerbation with admissions unrelated to HF or COPD (controls) as well as during disease stability.. We conducted a case-controlled observational study. Patients admitted to a tertiary teaching hospital for HF exacerbation (n = 37), COPD exacerbation (n = 26), and admissions unrelated to HF or COPD (controls, n = 60) were included. Warfarin sensitivity (INR per daily mg dose of warfarin) at admission was compared to periods of disease stability and also compared between the 3 groups.. The increase in warfarin sensitivity at admission was 94% for HF patients (P < 0.0001), 59% for COPD (P = 0.003) patients, and 24% for controls (P = 0.002). HF patients with New York Heart Association (NYHA) class 3 and 4 and NYHA class 1 and 2 experienced changes in warfarin sensitivity of 125% (P = 0.006) and 50% (P = 0.13) at admission. HF patients had higher warfarin sensitivity at admission (mean = 1.62 [SD = 1.27]) compared to the control group (0.91 [0.52], P < 0.0001) and COPD group (1.03 [0.79], P = 0.04). and required greater intervention with vitamin K than controls (14% vs 0%, P = 0.007).. HF and COPD patients were more sensitive to warfarin during disease exacerbation, with HF exacerbation having the largest impact, resulting in clinically significant management implications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Disease Progression; Female; Heart Failure; Hospitalization; Humans; International Normalized Ratio; Male; Pulmonary Disease, Chronic Obstructive; Vitamin K; Warfarin

Although atrial fibrillation (AF) occurs frequently in patients hospitalized with acute coronary syndrome (ACS), strategies for prevention of thromboembolic complications are poorly characterized.. We sought to examine exposure to warfarin and P2Y12 inhibitors and clinical outcomes among patients with AF and ACS.. Patients age >65 years hospitalized with a primary diagnosis of ACS and a secondary diagnosis of AF between 2007 and 2010 were identified in the Medicare 5% sample. Medication exposure was ascertained during a 90-day period following the index discharge using Medicare drug claims. Among patients who were alive and not readmitted during the ascertainment period, we examined the cumulative incidence of all-cause mortality and all-cause readmission by medication exposure at 1 year.. A total of 2509 Medicare beneficiaries met the inclusion criteria. Among the 1633 patients (65%) who were alive and not readmitted during the 90-day ascertainment period, 24.0% received warfarin, 38.9% received P2Y12 inhibitors, 10.2% received combination therapy, and 26.8% received neither therapy. Readmission rates were high in all groups at 1 year (warfarin, 47.5%; P2Y12 inhibitors, 46.6%; combination therapy, 38.0%; and neither therapy, 39.3%), and the overall 1-year mortality rate was 12.5%.. Among Medicare beneficiaries with AF and ACS, combination therapy with warfarin and P2Y12 inhibitor was uncommon during the 90-day ascertainment period, and more than one-quarter of patients had no claims for warfarin or P2Y12 inhibitors. Rates of all-cause readmission and mortality within 1 year of hospitalization for ACS were high.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Cellulitis; Comorbidity; Drug Therapy, Combination; Drug Utilization; Female; Gastrointestinal Diseases; Humans; Male; Medicare; Myocardial Revascularization; Patient Readmission; Pulmonary Disease, Chronic Obstructive; Purinergic P2Y Receptor Antagonists; Stents; Thromboembolism; United States; Warfarin

A 53-year-old man with lung adenocarcinoma developed pulmonary embolism and bilateral popliteal venous thrombosis. Treated with intravenous unfractionated heparin and discharged home on warfarin, he returned a week later with extending thrombosis. Treatment with heparin followed by warfarin was reinitiated. Twenty-four hours following the re-administration of warfarin, the patient's INR increased to 14.5. The platelet count dropped by more than 50%, and he developed venous limb gangrene of the left leg and skin necrosis of the right leg. Heparin-induced thrombocytopenia was ruled out, and coagulation studies showed a severe depletion of protein C as well as increased thrombin generation. The patient was transfused with fresh frozen plasma, and vitamin K was given. Heparin was continued, and after 4 weeks, the patient improved markedly showing only minimal necrosis of the toes. Venous limb gangrene is a major complication associated with warfarin therapy. Its pathogenesis is explained by a transient hypercoagulable state produced by protein C depletion that leads to microvascular thrombi progressing to venous limb gangrene. The present case emphasizes the importance of careful anticoagulation with heparin followed by slow initiation of low-dose warfarin, in order to minimize thrombotic complications.

Topics: Adenocarcinoma; Anticoagulants; Fatal Outcome; Gangrene; Heparin; Humans; Male; Middle Aged; Popliteal Vein; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Thrombosis; Warfarin