warfarin and Hyperlipidemias

We describe that high-dose methylprednisolone (20 mg/kg) can induce multifocal osteonecrosis (ON) in conjunction with thrombocytopenia, hypofibrinogenemia, and hyperlipemia. Detailed clinical and laboratory evaluations of coagulation system are recommended in those patients who develop manifestations of an abnormal lipid metabolism shortly after high-dose corticosteroid therapy. Moreover, we investigated the effects of the combination treatment with an anticoagulant (warfarin) plus a lipid-lowering agent (probucol) on prevention of steroid-induced osteonecrosis (ON) in this animal model. The incidence of ON in warfarin plus probucol (5%) was significantly lower than that observed in the control group (70%) (p <0.0001). Our results experimentally showed that the combined use of an anticoagulant and a lipid-lowering agent helps prevent steroid-induced ON in rabbits.

Topics: Animals; Anticholesteremic Agents; Anticoagulants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glucocorticoids; Humans; Hyperlipidemias; Methylprednisolone; Osteonecrosis; Probucol; Rabbits; Thrombocytopenia; Warfarin

Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usual approach has been opportunistic use of drug trials in unrelated patients, and to look for differences in response or outcome by "candidate gene" genotype, for example genes coding for drug metabolising enzymes (activators and metabolisers), and enzymes and receptors involved in lipid metabolism, adrenergic response, etc. As with all association studies, initially promising results have often failed the test of replication in larger studies, and the relationship between the CETP Taq-I variant and response to statins has now been disproved. The strongest data to date is the report [Chasman, D.I., Posada, D., Subrahmanyan, L., Cook, N.R., Stanton Jr., V.P., Ridker, P.M., 2004. Pharmacogenetic study of statin therapy and cholesterol reduction. J. Am. Med. Assoc. 291, 2821-2827] of a poorer cholesterol-lowering response to Pravastatin in the 7% of patients carrying a certain haplotype of the HMG CoA reductase gene (14% fall versus 19%), but if this is overcome simply by a higher dose, it is of little clinical relevance. Currently, the best example of avoiding side effects is determining genotype at the CYP2C9 locus with respect of warfarin treatment, since carriers for functional variants (>20% of the population) require lower doses for optimal anticoagulation, and homozygotes, although rare, may well experience serious bleeding if given a usual dose. The full potential of this field will only be realised with much further work.

Topics: Anticoagulants; Aryl Hydrocarbon Hydroxylases; Clinical Trials as Topic; Coronary Disease; Cytochrome P-450 CYP2C9; Genetic Testing; Genotype; Hemorrhage; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Pharmacogenetics; Polymorphism, Single Nucleotide; Pravastatin; Warfarin

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient's goal INR. The literature supports a drug interaction between warfarin and fluvastatin due to the strong affinity of fluvastatin for the cytochrome P450 enzyme 2D6. This interaction has not been seen with atorvastatin. Lovastatin also reportedly has caused increases in INR when coadministered with warfarin. It is unclear whether simvastatin interacts with warfarin, but it may increase INRs slightly or increase serum simvastatin levels. One case report describes an interaction between simvastatin and the anticoagulant acenocoumarol, which resulted in an elevated INR. Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione. Thus, until more definitive data are available, clinicians should monitor the INR closely after starting statin therapy in any patient receiving anticoagulation therapy.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atorvastatin; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; International Normalized Ratio; Male; Patient Compliance; Pyrroles; Simvastatin; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Antihypertensive Agents; Atrial Fibrillation; Cerebral Infarction; Contraindications; Diabetes Complications; Humans; Hyperlipidemias; Hypertension; Risk Factors; Smoking; Thrombolytic Therapy; Warfarin

Topics: Anticoagulants; Antipyrine; Arginine; Aspirin; Brain Edema; Edaravone; Fibrinolytic Agents; Free Radical Scavengers; Glycerol; Humans; Hyperlipidemias; Hypertension; Japan; Methacrylates; Pipecolic Acids; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Factors; Stroke; Sulfonamides; Thrombolytic Therapy; Time Factors; Warfarin

This overview summarizes the pathophysiology of acute myocardial infarction and reviews existing strategies for secondary prevention of myocardial infarction. The review also examines the complex interactions among lipids and the hemostatic/fibrinolytic systems to delineate the importance of lipid reduction as a secondary prevention measure.. Information gathered includes studies related to the pathogenesis of acute myocardial infarction, secondary prevention of myocardial infarction, hyperlipidemia and the hemostatic/fibrinolytic systems. All studies cited were published prior to 1993.. Atherosclerotic plaque rupture with occlusive thrombus formation is integral to the pathophysiology of acute myocardial infarction. Beta-blockers, acetylsalicylic acid, warfarin, and angiotensin-converting enzyme inhibitors are useful agents for secondary prevention. The myriad deleterious effects of hyperlipidemia that promote a prothrombotic and antifibrinolytic vascular milieu serve to elucidate the importance of lipid reduction as an additional secondary prevention measure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Combined Modality Therapy; Coronary Artery Disease; Coronary Circulation; Humans; Hyperlipidemias; Hypolipidemic Agents; Myocardial Infarction; Thrombolytic Therapy; Warfarin

This study aimed to investigate the effectiveness of monotherapy acetylsalicylic acid (ASA) and warfarin for stroke prevention in low-risk atrial fibrillation (AF) by using a population- -based cohort study in Taiwan.. A newly diagnosed low-risk AF patient cohort were identified by using National Health Insurance Research Database (NHIRD) in Taiwan in 2008. The study cohort was observed with a follow-up of 2 years to examine the onset of ischemic stroke (IS) (to 2010). The longitudinal data were analyzed by using generalized estimation equations (GEE).. A total of 8,065 newly-diagnosed low-risk AF patients were identified in 2008. 7.4% were prescribed with ASA and 4.6% were prescribed with warfarin. The GEE results showed that low-risk AF patients with hypertension who received warfarin were associated with a statistically significant 58.4% reduction of IS risk (OR = 0.416, p = 0.024, 95% CI 0.194-0.891). Additionally, low-risk AF patients with hyperlipidemia who received warfarin were associated with a 69.3% reduction of IS risk (OR = 0.307, p = 0.044, 95% CI 0.097-0.969).. Warfarin is suggested to be prescribed in preventing IS for low-stroke-risk AF patients with hypertension and hyperlipidemia.

Topics: Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Comparative Effectiveness Research; Databases, Factual; Female; Humans; Hyperlipidemias; Hypertension; Incidence; Male; Middle Aged; Risk Assessment; Risk Factors; Stroke; Taiwan; Time Factors; Treatment Outcome; Warfarin; Young Adult

Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) cause significant visual impairment. The role of thrombophilia and cardiovascular testing is uncertain, and optimal treatment strategies have not been determined. We reviewed medical records of 39 patients with RVO and RAO (23 women and 16 men). Thrombophilia and cardiovascular evaluations were performed and outcomes were reviewed. In all, 24 (61.5%) patients had at least 1 thrombophilia. Elevated factor VIII levels were found in RVO (n = 5) but not in RAO. There are no other significant differences in thrombophilias in RVO compared to those in RAO. Most patients had hypertension(41.2% RAO and 55% RVO) and hyperlipidemia (35.5% RAO and 81.8% RVO). In all, 4 women were using oral contraceptives, 2 were pregnant or postpartum. Follow-up data was available for 28 patients (13 RAO, 15 RVO). Nineteen were treated with aspirin, four with warfarin, and one with low molecular weight heparin. Eight patients reported improvement in vision at time of follow-up (5 RAO, 3 RVO). Multiple risk factors are associated with RVO and RAO, and a complete assessment should include thrombophilia and cardiovascular studies.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Postpartum Period; Pregnancy; Pregnancy Complications; Retinal Vein Occlusion; Retrospective Studies; Risk Factors; Thrombophilia; Warfarin

Persistently elevated antiphospholipid antibodies and positive lupus anticoagulant (LAC) are associated with an increased risk of thrombosis. The objective of this study was to explore whether antiphospholipid antibody and/or LAC positivity were associated with the traditional risk factors for thrombosis or with medication use in patients without autoimmune diseases hospitalised with arterial or venous thrombosis.. Cross-sectional study.. Montefiore Medical Center, a large urban tertiary care centre.. 270 patients (93 with deep vein thrombosis (DVT) or pulmonary embolism (PE), and 177 with non-haemorrhagic stroke (cerebrovascular accident (CVA)) admitted between January 2006 and December 2010 with a discharge diagnosis of either DVT, PE or CVA, who had LAC and antiphospholipid antibodies measured within 6 months from their index admission. Patients with lupus or antiphospholipid syndrome were excluded.. The main dependent variable was antiphospholipid antibodies of 40 units or greater (antiphospholipid antibody positivity) and/or LAC positivity. Independent variables were traditional thrombosis risk factors, statin use, aspirin use and warfarin use.. 31 (11%) patients were LAC positive and/or antiphospholipid antibody positive. None of the traditional risk factors at the time of DVT/PE/CVA was associated with antiphospholipid antibody positivity. Current statin use was associated with an OR of 3.2 (95% CI 1.3 to 7.9, p=0.01) of antiphospholipid antibody positivity, adjusted for age, ethnicity and gender. Aspirin or warfarin use was not associated with antiphospholipid antibody levels.. If statin therapy reflects the history of previous hyperlipidaemia, high levels of antiphospholipid antibodies may be a marker for earlier endothelial damage caused by hyperlipidaemia.

Topics: Aged; Antibodies, Antiphospholipid; Aspirin; Biomarkers; Chronic Disease; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lupus Coagulation Inhibitor; Male; Middle Aged; Pulmonary Embolism; Risk Factors; Stroke; Venous Thrombosis; Warfarin

Patients with atrial fibrillation (AF) on treatment with oral anticoagulants may still suffer ischemic cerebrovascular events. The aim of this study was to evaluate the risk factors for cerebral ischemic events in warfarin-treated AF patients with an International Normalized Ratios (INR) above 1.8 on admission.. In a case-control study, cases were consecutive patients with AF who were on warfarin and who were admitted to four Italian hospitals after an acute cerebrovascular ischemic event (ischemic stroke or transient ischemic attack) with an INR above 1.8. Controls were selected from a single anticoagulation clinic and were patients with AF on adequate warfarin treatment who did not suffer cerebrovascular events.. Cases were identified among 4785 consecutive patients with an ischemic cerebral event. 148 cases (3.1%, 21 with transient ischemic events and 127 with ischemic strokes) had AF and were taking warfarin with an INR above 1.8 on admission. On multivariate analysis, diabetes (OR 3.8; 95% CI 1.09-13.82, p=0.025), hyperlipidemia (OR 4.5; 95% CI 1.11-18.23, p=0.035) and carotid/vertebral atherosclerosis on ultrasound (OR 3.0; 95% CI 1.13-8.41, p=0.028) were independent predictors for ischemic cerebral events. The use of statins was inversely correlated with an ischemic event (OR 0.1; 95% CI 0.06-0.47. p=0.001).. Carotid/vertebral atherosclerosis, diabetes and hyperlipidemia are associated with an increased risk for ischemic events in patients with AF on adequate warfarin treatment. Statins significantly reduce the risk of ischemic events.

Topics: Aged; Anticoagulants; Atherosclerosis; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Female; Humans; Hyperlipidemias; Male; Middle Aged; Multivariate Analysis; Risk; Stroke; Warfarin

This study assesses whether competitive displacement of clozapine by warfarin affects clozapine's overall plasma distribution.. Warfarin sodium was preincubated in normolipidemic and hyperlipidemic plasma samples in varying concentrations. Following the preincubation with warfarin, [3H]clozapine mixed with unlabeled clozapine was added to the plasma samples. The plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradient ultracentrifugation, and clozapine distribution was determined.. When normolipidemic plasma was preincubated with various concentrations of warfarin, no significant redistribution of clozapine was noted among the various plasma lipoprotein fractions. However, in the case of the hyperlipidemic plasma, preincubating with warfarin did result in a significant redistribution of clozapine from the lipoprotein-deficient fraction to the very-low-density and low-density fractions of lipoproteins. Based on pharmacokinetic principles, the steady-state unbound concentration of clozapine in normolipidemic and hyperlipidemic plasma is not expected to change.. Although no change in the steady-state unbound (active) concentration of clozapine would predict no change in clinical status, it is possible that this may only apply to the individuals with a normal lipid profile. We believe clozapine's association with lipoproteins (particularly triglycerides) may actually increase clozapine's effectiveness.

Topics: Algorithms; Binding, Competitive; Blood Proteins; Centrifugation, Density Gradient; Cholesterol, HDL; Cholesterol, VLDL; Clinical Laboratory Techniques; Clozapine; Dose-Response Relationship, Drug; Humans; Hyperlipidemias; Lipoproteins, LDL; Technology, Pharmaceutical; Tritium; Warfarin

To assess whether dyslipidemia affects haloperidol's overall plasma distribution when it is in the presence of another highly protein bound drug that competes for plasma protein binding sites.. We performed in vitro studies in which warfarin sodium was pre-incubated in normolipidemic and hyperlipidemic plasma samples in varying concentrations. Following the pre-incubation with warfarin, [3H]-haloperidol mixed with unlabeled haloperidol was added to the plasma samples. The plasma was separated into its lipoprotein and lipoprotein deficient fractions by density gradient ultracentrifugation and haloperidol distribution was determined.. Our results indicate that when normolipidemic plasma was pre-incubated with various concentrations of warfarin no significant redistribution of haloperidol was noted among the various plasma lipoprotein fractions. However, in the case of the hyperlipidemic plasma, pre-incubating with warfarin did result in a significant redistribution of haloperidol from the lipoprotein-deficient fraction to the very-low-density and low-density fractions of lipoproteins.. Understanding how plasma lipoproteins influence competitive displacement interactions would be valuable in helping to explain and perhaps predict pharmacokinetic parameters that may affect clinical outcome. The clinical significance of competitive displacement of drugs in patients with dyslipidemia requires further study.

Topics: Anticoagulants; Antipsychotic Agents; Binding, Competitive; Blood Proteins; Haloperidol; Humans; Hyperlipidemias; In Vitro Techniques; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Warfarin

To determine vascular risk factor (VRF) profiles in transient ischemic attack (TIA) and ischemic stroke.. We studied 239 patients with TIA and 1,473 ischemic stroke patients included in a prospective stroke registry over a 10-year period.. Main VRF were: hypertension, hyperlipidemia, diabetes mellitus and atrial fibrillation. In the multivariate analysis, prior ischemic stroke (OR=1.65; 95% CI, 1.07-2.56), atrial fibrillation (OR=1.60; 95% CI, 1.14-2.26) and current use of warfarin treatment (OR=0.34; 95% CI, 0.13-0.94) were the only independent risk factors associated with ischemic stroke.. Different potentially modifiable vascular risk factor profiles were identified in ischemic stroke versus TIA. This suggests that there are pathogenic differences between TIA and ischemic strokes.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain; Cerebral Infarction; Diabetes Complications; Female; Humans; Hyperlipidemias; Hypertension; Ischemic Attack, Transient; Male; Multivariate Analysis; Predictive Value of Tests; Risk Factors; Surveys and Questionnaires; Warfarin

To investigate the relationship among lipids, coagulation and thrombosis in the absence of atherosclerosis, spontaneous or dietary-induced hyperlipidemic (FHL) rats were studied. FHL showed higher levels of coagulation factors VII, IX, X, VIII and XII and a shortening of the occlusion time (OT) of an artificial arterial prosthesis as compared with normolipidemic (FNL) animals. Damage of abdominal aorta of FHL was followed by increased fibrin deposition in the vascular intima as compared to FNL. After 5 months of cholesterol-rich diet FNL showed increased cholesterol, triglycerides and factor II, VII, IX, X, XII levels. A significant shortening of the OT and increased fibrin deposition was also observed. Two-month diet withdrawal restored the initial condition. Warfarin treatment, at a dose decreasing vitamin K-dependent factor to levels found in FNL, prolonged the OT and reduced fibrin deposition, without modifying F XII or changing lipid profile. An increase in the activated form of F VII was observed. In contrast, no difference was found in F VII clearance. High lipid levels favour the process of thrombus formation by increasing the activation of vitamin K-dependent coagulation factors. Low-dose warfarin treatment reverts the prothrombotic effect of hyperlipidemia.

Topics: Administration, Oral; Animals; Anticoagulants; Aorta, Abdominal; Aortic Diseases; Blood Coagulation Factors; Blood Vessel Prosthesis; Cholesterol, Dietary; Diet, Atherogenic; Disease Models, Animal; Enzyme Activation; Factor VII; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Postoperative Complications; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Thrombophilia; Thrombosis; Vitamin K; Warfarin

The following describes a patient on a stable regimen of warfarin who developed severe hypoprothrombinemia and bleeding 4 weeks after starting gemfibrozil. Despite a warning by the manufacturer, only one report of this interaction has been published in the literature. This interaction may be overlooked by clinicians, which may result in a serious bleeding risk for patients on warfarin.

Topics: Aged; Anticoagulants; Drug Interactions; Follow-Up Studies; Gemfibrozil; Hemorrhage; Humans; Hyperlipidemias; Hypolipidemic Agents; Hypoprothrombinemias; Male; Thrombophlebitis; Warfarin

Topics: Aged; Anticoagulants; Bezafibrate; Blood Coagulation Disorders; Drug Synergism; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; International Normalized Ratio; Male; Warfarin

Topics: Adult; Aged; Angina Pectoris; Arrhythmias, Cardiac; Cholesterol; Cholestyramine Resin; Clofibrate; Diet; Female; Heart Failure; Humans; Hyperlipidemias; Hyperthyroidism; Male; Middle Aged; Myocardium; Oxygen Consumption; Pacemaker, Artificial; Propranolol; Warfarin

Topics: Anticholesteremic Agents; Anticoagulants; Arteriosclerosis; Cholesterol; Choline; Diabetes Complications; Dicumarol; Humans; Hyperlipidemias; Hypertension; Nicotinic Acids; Obesity; Phospholipids; Smoking; Stress, Physiological; Thyroxine; Vasodilator Agents; Warfarin

Topics: Acetohexamide; Adult; Agglutination; Angina Pectoris; Anticholesteremic Agents; Arteriosclerosis; Body Weight; Butyrates; Chlorpropamide; Cholesterol; Conjunctiva; Diabetes Complications; Diabetic Neuropathies; Diet, Reducing; Female; Heart Diseases; Humans; Hypercholesterolemia; Hyperlipidemias; Male; Middle Aged; Phenformin; Triglycerides; Warfarin; Xanthomatosis

Topics: Adult; Aged; Blood Coagulation Factors; Cholesterol; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Male; Middle Aged; Receptors, Drug; Triglycerides; Warfarin

Topics: Adult; Blood Coagulation Factors; Cholesterol; Coronary Disease; Drug Synergism; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipids; Male; Triglycerides; Warfarin

Topics: Androsterone; Anticoagulants; Butyrates; Clofibrate; Coronary Disease; Hypercholesterolemia; Hyperlipidemias; Phenindione; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Cholesterol; Coronary Disease; Dicumarol; Hyperlipidemias; Iodine Isotopes; Lipids; Trichloroacetic Acid; Triolein; Warfarin