warfarin and Arteriosclerosis

Arteriosclerosis, characterized by remodeling and stiffening of large elastic arteries is the most significant manifestation of vascular aging. The increased stiffening is believed to originate from a gradual mechanical senescence of the elastic network, alterations in cross-linking of extracellular matrix components, fibrosis and calcification of elastic fibers (medial elastocalcinosis). The stiffening of large arteries reduces their capacitance and accelerates pulse wave velocity, thus contributing to a widening of pulse pressure and to the increased prevalence of isolated systolic hypertension with age. Current antihypertensive drugs were mainly designed to reduce peripheral resistance and are not adequate to alter the pathological process of vascular stiffening or even to selectively reduce systolic blood pressure in isolated systolic hypertension. This review puts forward the concept that elastocalcinosis is a valuable therapeutic target and presents evidence that this process can be prevented and reversed pharmacologically.

Topics: Aged; Aging; Antihypertensive Agents; Arteries; Arteriosclerosis; Calcinosis; Humans; Hypertension; Muscle, Smooth, Vascular; Osteoporosis; Systole; Vitamin K; Warfarin

THE CONTEXT: The demonstration of the efficacy of oral anticoagulants in the secondary prevention of ischemic stroke represents a major progress in medicine in the last twenty years. Efficacy in fact depends on the causes and this determines the indications. ADMITTED AND DEMONSTRATED INDICATIONS: Cardiac arrhythmia due to atrial fibrillation and the existence of mechanical prosthetic valves are the only two indications that have been demonstrated with sufficient proof. ADMITTED NON-DEMONSTRATED INDICATIONS: These are basically the dissection of cervical arteries, aortal cross atheroma, vascular cerebral accidents within the context of antiphospholipid antibody syndromes. POSSIBLE INDICATIONS: There are three: stenosis of the intra-cranial arteries, patent foramen ovale with atrial septum aneurysm and the basilar dolichoectasia trunks. NON-DEMONSTRATED SUPERIORITY: In atherosclerosis-induced cerebral ischemic accidents.

Topics: Anticoagulants; Antiphospholipid Syndrome; Arteriosclerosis; Aspirin; Atrial Fibrillation; Cardiovascular Diseases; Clinical Trials as Topic; Drug Therapy, Combination; Fibrinolytic Agents; Heart Valve Prosthesis; Humans; Intracranial Arterial Diseases; Platelet Aggregation Inhibitors; Primary Prevention; Retrospective Studies; Risk; Risk Factors; Stroke; Time Factors; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Aspirin; Atrial Fibrillation; Cerebral Infarction; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Meta-Analysis as Topic; Platelet Aggregation Inhibitors; Secondary Prevention; Ticlopidine; Warfarin

Antiphospholipid syndrome is the most frequent cause of acquired thrombophilia. Aspirin may have some indications. CURRENT KONWLEDGE AND KEY POINTS: The usefulness of low doses of aspirin is now well demonstrated in the prevention of obstetric complications associated with antiphospholipid antibodies (especially pregnancy loss). When heparin is combined with low-dose aspirin, the recurrent rate of fetal loss is lower than 30%. In patients with arterial or venous thrombosis, there is a high rate of recurrence during the two first years except if high-dose warfarin was used (i.e., INR > or = 3). The association warfarin-aspirin in secondary prevention of thrombosis may be evaluated in prospective studies. It is not so clear in the literature and in our experience that warfarin is superior to aspirin in stroke recurrence prevention in patients with antiphospholipid antibodies, except in Sneddon's syndrome. There are no guidelines in primary thrombosis prevention in patients with antiphospholipid antibodies. In lupus patients, aspirin may not be sufficient after many years of follow-up in preventing a first episode of thrombosis. Prospective studies may be undertaken. Atherosclerotic patients with antiphospholipid antibodies are particularly exposed to the risk of thrombosis after revascularisation or angioplasty and stent implantation. Aspirin may have a place in those patients but these must be evaluated. FUTUR PROSPECTS AND PROJECTS: Except in prevention of obstetric complications, the usefulness of aspirin in patients with antiphospholipid antibodies must be evaluated in prospective studies.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antiphospholipid Syndrome; Arteriosclerosis; Aspirin; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Female; Fetal Death; Fibrinolytic Agents; Humans; Male; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications; Primary Prevention; Recurrence; Risk Factors; Thrombosis; Warfarin

The cytochrome P450 (CYP) is a group of enzymes that oxidatively modify drugs to a more water-soluble form for renal excretion. Nearly 50% of all clinically used medications and endogenous steroids are metabolized by the CYP enzyme 3A4, which explains why many of the important potential drug interactions involved this enzyme. Despite an excellent safety record, CYP 3A4 statins (lovastatin, simvastatin, atorvastatin) taken concomitantly with a potent CYP 3A4 inhibitor may increase the risk for adverse events (myopathy, rhabdomyolysis). This article describes the clinical significance of CYP metabolism as the pathways relate to the use of statins, including brief discussions on statins, fibrates, cyclosporine, and calcium channel blockers. In light of these potential interactions, continued vigilance by physicians is necessary to ensure the safe use of statins.

Topics: Anticoagulants; Arteriosclerosis; Calcium Channel Blockers; Cyclosporine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Humans; Hypolipidemic Agents; Immunosuppressive Agents; Mixed Function Oxygenases; Niacin; Polymorphism, Genetic; Risk Factors; Warfarin

The consensus on antithrombotic prophylaxis of vascular incidents in patients with manifest atherosclerotic vasculopathy was preceded by a systematic classification of results from relevant articles according to 'evidential value': from randomized prospective trials of sufficient quality and size, via less adequate or non-randomized trials to the current opinion in the Netherlands. The principal advice was to prescribe antithrombotic prophylaxis, mostly acetylsalicylic acid, for patients with manifest atherosclerotic vasculopathy (in head, heart and (or) legs). With regard to the question what drug should be preferred for patients with intermittent claudication, no consensus could be reached for lack of adequate research. Acetylsalicylic acid is not more effective in higher than in lower doses, but in higher doses it has more side effects; therefore lower doses are preferred: 80-100 mg per day, and for neurological indications, 30 mg or more per day. Use of coumarin derivates is only to be preferred in patients with atrial fibrillation who have suffered a TIA or a non-crippling cerebral infarction, in patients with atrial fibrillation and a cardiac disorder such as large myocardial infarction or a left ventricular aneurysm, and in patients who have undergone a cardiac valve operation. Since the proportion of pros and cons of antithrombotic prophylaxis may change during a patient's life, the indication should be reconsidered periodically.

Topics: Anticoagulants; Arteriosclerosis; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Coronary Disease; Fibrinolytic Agents; Humans; Ischemic Attack, Transient; Myocardial Infarction; Platelet Aggregation Inhibitors; Warfarin

Cardiac causes of stroke account for approximately 20% of strokes occurring in the United States. Transthoracic echocardiography (TTE) remains the cornerstone of non-invasive cardiac imaging, but transesophageal echocardiography (TEE) is superior for identifying potential cardiac sources of emboli, including left atrial thrombi, valvular vegetations, thoracic aortic plaque, patent foramen ovale, and spontaneous left atrial echocardiographic contrast. The diagnostic yield of TEE for potential cardiac causes of thromboembolism exceeds 50%. The impact of TEE on the clinical management of this group, however, remains undefined for most TEE-specific diagnoses. Thus, routine use of TEE in these patients has been questioned. The diagnostic yield is highest if the clinical history/physical examination suggests a cardiac source. However, the clinical scenario often dictates patient management, and TEE data are used to "validate" the clinical impression. Data from large, prospective, randomized (aspirin/warfarin) studies, in which TEE data are obtained from patients with suspected cardiac thromboembolism, are needed. If specific TEE diagnoses can be identified in which defined therapies are beneficial, "source of embolism" will continue to be the most common indication for TEE referral. In this paradigm, TEE (without initial TTE) will probably become a more direct diagnostic pathway. However, if these studies demonstrate that all patients with suspected cardiac source benefit from one (or no) therapy, independent of TEE data, referrals for TEE will decline. Results of ongoing randomized trials to evaluate the efficacy of TEE in patients with cryptogenic stroke or transient ischemic attack are awaited.

Topics: Anticoagulants; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Aspirin; Cerebrovascular Disorders; Echocardiography, Transesophageal; Heart Atria; Heart Diseases; Heart Septal Defects, Atrial; Heart Valve Diseases; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Medical History Taking; Physical Examination; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Referral and Consultation; Reproducibility of Results; Thrombosis; Treatment Outcome; Warfarin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arteriosclerosis; Aspirin; Brain Ischemia; Carotid Stenosis; Endarterectomy, Carotid; Humans; Warfarin

The basic mechanisms of atherosclerotic progression leading to the acute coronary syndromes (ACS) have been elucidated during the last few years. In this brief presentation, we outline 1) Definition of Atherosclerotic Lesions: eight morphologically different lesions are defined (Type I to VI) in various phases of disease. 2) Vulnerable Lipid-Rich Plaques and the ACS: The type IV and Va lesions tend to be relatively small in size, but soft or vulnerable to a "passive" phenomenon of plaque disruption; in addition, an "active" macrophage-dependent enzymatic (genesis of metalloproteinase) phenomenon of plaque disruption is evolving. 3) Thrombosis: we have shown that monocytes/macrophages in lipid-rich plaques may play a detrimental role after plaque disruption, promoting thrombin generation and thrombosis through the tissue factor pathway that can be prevented by tissue factor pathway inhibition; such pathway of thrombosis appears to be critical in the development of the ACS. 4) Effect of Lipid-Modifying Strategies and other Risk Factors on the Vulnerable Lipid-Rich Plaques: when high LDL-cholesterol is reduced therapeutically, efflux from the plaques of the liquid or sterified cholesterol, and also its hydrolysis into cholesterol crystals depositing in the vessel wall, predominate over the influx of LDL-cholesterol; consequently, there is a decrease in the softness of the plaque and so, presumably in the "passive" phenomenon of plaque disruption; modification of other risk factors presumably also favorably affect LDL-cholesterol influx and efflux. 5) Antithrombotic Strategies: the evolving antithrombotic approaches under investigation are briefly outlined.

Topics: Anticoagulants; Arteriosclerosis; Aspirin; Clinical Trials as Topic; Coronary Thrombosis; Disease Progression; Drug Therapy, Combination; Endothelium, Vascular; Fibrinolytic Agents; Humans; Lipids; Models, Biological; Platelet Aggregation Inhibitors; Rupture, Spontaneous; Thromboembolism; Thromboplastin; Warfarin

Topics: Animals; Antioxidants; Arteriosclerosis; Aspirin; Calcium Channel Blockers; Fibrinolytic Agents; Heparin; Humans; Probucol; Rabbits; Vitamins; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Brain Ischemia; Cerebrovascular Disorders; Heparin; Humans; Intracranial Embolism and Thrombosis; Neurology; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Coronary Disease; Drug Interactions; Fibrinolysis; Heart Diseases; Heart Valve Prosthesis; Hemolysis; Hemostasis; Heparin; Humans; Myocardial Infarction; Platelet Aggregation; Pulmonary Embolism; Stress, Physiological; Thrombophlebitis; Warfarin

The POST CABG (Post Coronary Artery Bypass Graft) Trial showed that aggressive lowering of low-density lipoprotein (LDL) cholesterol levels reduced the progression of atherosclerosis in saphenous vein grafts. In the extended follow-up phase, aggressive lowering of LDL cholesterol levels was associated with reduced rates of clinical events. Low-dose anticoagulation therapy did not reduce the progression of atherosclerosis. We conducted this analysis to determine the effects of both lipid-lowering and low-dose anticoagulation therapy on health-related quality of life (HRQL).. Randomized clinical trial, factorial design.. Outpatients in five tertiary care medical centers.. A cohort of 852 patients enrolled in the POST CABG Trial completed an HRQL questionnaire at baseline, and at the year 2 and year 4 follow-up visits.. Aggressive LDL cholesterol lowering vs moderate LDL cholesterol lowering, and low-dose warfarin vs placebo.. Domains included emotional status, basic physical and social functioning, perceived health status, symptoms of pain, a variety of physical symptoms, and global life satisfaction.. Overall, there were no indications of systematic differences among treatment groups for any of the HRQL parameters at baseline, year 2, or year 4.. These data indicate that patients did not experience detrimental or beneficial effects on HRQL parameters while receiving LDL cholesterol-lowering therapy that had demonstrable benefits for treatment of atherosclerosis.

Topics: Anticoagulants; Arteriosclerosis; Cholesterol, LDL; Coronary Artery Bypass; Disease Progression; Female; Humans; Male; Postoperative Care; Quality of Life; Surveys and Questionnaires; Warfarin

Patients with peripheral arterial disease (PAD) are at an increased risk of cardiovascular mortality and morbidity and thus are an excellent group in whom to evaluate the feasibility and the effect of an aggressive multifactorial intervention on atherosclerotic vascular disease risk factors. The Arterial Disease Multiple Intervention Trial (ADMIT) was designed to determine the efficacy, safety, and compliance of an multifactorial therapy on selected atherosclerotic disease risk factors in patients with PAD.. By a 2 x 2 x 2 factorial design, eligible participants (N = 468) were randomly assigned to low-dose warfarin, antioxidant vitamins, and niacin or its corresponding placebo, and followed up for 1 year. All participants were encouraged to use aspirin. Pravastatin was added to the drug regimen for those who needed to reduce LDL cholesterol to recommended levels.. Niacin increased HDL cholesterol levels by 30%, with the majority of effect achieved at a dosage of 500 mg twice daily. Warfarin had an anticoagulant effect. The antioxidant vitamins resulted in a significant increase in vitamin E, C, and beta-carotene plasma levels. Overall, compliance was high and few adverse effects were reported.. ADMIT demonstrates that it is both feasible and safe to modify multiple atherosclerotic disease risk factors effectively with intensive combination therapy in patients with PAD.

Topics: Aged; Anticholesteremic Agents; Anticoagulants; Antioxidants; Arteriosclerosis; Aspirin; Cholesterol, LDL; Feasibility Studies; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Niacin; Platelet Aggregation Inhibitors; Pravastatin; Risk Factors; Self Medication; Time Factors; Treatment Outcome; Triglycerides; Vitamins; Warfarin

Patients with atrial fibrillation and with documented aortic plaque who were assigned to adjusted-dose warfarin therapy (international normalized ratio 2.0 to 3.0) had an annual rate of cholesterol embolization of 0.7% (95% confidence interval [CI] 0.1% to 5.3%/patient-year). Warfarin-assigned patients with plaque had a lower rate of embolic events (5.9%/year; 95% CI 3.0 to 12) than those on combination low-dose warfarin (international normalized ratio <1.5) plus aspirin (17.3%/year; 95% CI 11 to 27; p = 0.01).

Topics: Aged; Anticoagulants; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Aspirin; Atrial Fibrillation; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Safety; Thromboembolism; Treatment Outcome; Warfarin

Few clinical trials have documented the efficacy of preventive treatment in asymptomatic women.. Lovastatin and minidose warfarin were evaluated in a factorially designed, placebo-controlled, randomized trial. The primary outcome was 3-year change in the mean maximum intimal-medial thickness of the carotid arteries as measured by B-mode ultrasonography. Participants (n=919) were randomized to 1 of 4 treatment groups: lovastatin alone, warfarin alone, lovastatin+warfarin combination, or a double-placebo group. Eligible participants were asymptomatic for cardiovascular disease, with evidence of early carotid atherosclerosis and moderately elevated LDL cholesterol level. Almost half (n=445) of the participants were women. To avoid confounding, 117 women taking estrogen were excluded from analysis. Both sexes experienced reductions in disease progression with lovastatin; there was no evidence of an overall sex x treatment interaction (P=0.72). When estimates of the sex-specific results were examined post hoc, women experienced disease regression to the greatest extent with the lovastatin + warfarin combination (P=0.02), although the women on lovastatin alone also had a reduction in progression (P=0.09). Men experienced the greatest reduction with lovastatin alone (P=0.02), although there is a suggestion that warfarin may also reduce progression to some extent.. Lovastatin is beneficial in reducing disease progression in women and men. Warfarin has no effect in women, although it may reduce progression in men. In men, warfarin does not add to the benefit of lovastatin and has no advantage over lovastatin alone.

Topics: Adult; Aged; Arteriosclerosis; Carotid Artery Diseases; Carotid Artery, Common; Carotid Artery, Internal; Cholesterol, LDL; Disease Progression; Double-Blind Method; Factor Analysis, Statistical; Female; Follow-Up Studies; Humans; Lovastatin; Male; Middle Aged; Sex Characteristics; Ultrasonography; Warfarin

Transesophageal echocardiography (TEE) visualizes potential sources of embolism in patients with atrial fibrillation, but the clinical significance of TEE findings has not been prospectively established.. To define TEE predictors of stroke in patients with atrial fibrillation and to examine response to antithrombotic therapy.. Prospective correlation of TEE findings at study entry with subsequent ischemic stroke during 1.1-year mean follow-up of participants in a randomized trial.. 18 echocardiography laboratories.. 382 patients with atrial fibrillation at high risk for thromboembolism.. Adjusted-dose warfarin (international normalized ratio, 2 to 3) or low-intensity warfarin (international normalized ratio, 1.2 to 1.5) plus aspirin (325 mg/d).. Size of left atrium and left atrial appendage, flow velocity, spontaneous echocardiographic contrast, thrombus, and plaque on the aortic arch.. 23 ischemic strokes occurred. In patients with dense spontaneous echocardiographic contrast (20%), the rate of stroke was 18.2% per year with combination therapy (2.9 times the rate in patients without this finding; P = 0.06) and 4.5% per year with adjusted-dose warfarin (P = 0.09 for rate reduction). Appendage thrombus, detected in 10% of patients, was associated with dense spontaneous echocardiographic contrast (P < 0.001), was seen more frequently after 2 weeks of combination therapy (15%) than after 2 weeks of adjusted-dose warfarin (4%) (P = 0.004), and tripled the overall rate of stroke (P = 0.04). Patients with complex aortic plaque (35%) had a fourfold increased rate of stroke compared with plaque-free patients (P = 0.005); adjusted-dose warfarin decreased risk by 75% (P = 0.02). Dense spontaneous echocardiographic contrast and complex aortic plaque were independent of each other as predictors of thromboembolism.. In high-risk patients with atrial fibrillation, subsequent rates of thromboembolism are correlated with dense spontaneous echocardiographic contrast, thrombus of the atrial appendage, and aortic plaque. Adjusted-dose warfarin reduces the rate of stroke among patients with dense contrast and complex plaque. In patients with atrial fibrillation, the pathogenesis of stroke is multifactorial, and warfarin seems effective for the diverse mechanisms.

Topics: Aged; Anticoagulants; Aortic Diseases; Arteriosclerosis; Aspirin; Atrial Fibrillation; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Atria; Heart Diseases; Humans; Male; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Thromboembolism; Warfarin

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have proven to be more effective in reducing levels of low density lipoprotein (LDL) cholesterol and to be better tolerated than other lipid-lowering compounds. Most of the trials evaluating the effects of these new agents on progression of atherosclerosis have not included individuals asymptomatic for cardiovascular disease and who have LDL cholesterol levels at or below the limits established by the National Cholesterol Education Program for initiating treatment. The Asymptomatic Carotid Artery Progression Study (ACAPS) tested the effect of the HMG-CoA reductase inhibitor, lovastatin, on early-stage carotid atherosclerosis (as detected by B-mode ultrasonography) in 919 asymptomatic men and women, 40-79 years of age, who had LDL cholesterol levels between the 60th and 90th percentiles. Participants randomized into this double-blind, placebo-controlled, factorially designed study received lovastatin (20-40 mg/day) or lovastatin-placebo and warfarin (1 mg/day), or warfarin-placebo over a 3-year period. The progression of the mean maximum intimal-medial thickness (IMT) over 12 walls of both carotid arteries represented the primary outcome. Lovastatin treatment was associated with a reduction in progression of mean maximum IMT (p < 0.001). Levels of LDL cholesterol were reduced by 28% (43.5 mg/dl [11.25 mmol/liter]) in the lovastatin group within 6 months (p < 0.0001) and remained stable throughout the follow-up period, whereas these levels remained essentially unchanged in the lovastatin-placebo group. The difference in incidence of major cardiovascular events for patients in the lovastatin-placebo group was significant: 5 versus 14, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anticholesteremic Agents; Anticoagulants; Arteriosclerosis; Carotid Arteries; Carotid Artery Diseases; Cholesterol, LDL; Double-Blind Method; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Male; Middle Aged; Multivariate Analysis; Regression Analysis; Treatment Outcome; Ultrasonography; Warfarin

We analyzed a current 78-month experience with externally supported (ringed) polytetrafluoroethylene (PTFE) axillobifemoral (AxBF) and axillounifemoral (AxUF) bypass grafts to address the controversy about whether the addition of a femorofemoral limb to an axillofemoral bypass graft improves the patency results.. Between January 1988 and June 1994, 36 AxBF and 22 AxUF externally supported PTFE ringed bypass grafts were performed at our institution. The age of the patients in the AxBF group was 67 +/- 11 years and 69 +/- 11 years in the AxUF group. The male/female ratio was 22:13 (AxBF) and 8:9 (AxUF). In 71% of cases (29/36 AxBF, 12/22 AxUF), the operations were performed for aortoiliac atherosclerotic occlusive disease in patients with significant medical risk factors or a "hostile" abdomen. The remaining 29% were patients requiring revascularization during treatment of an infected aortic graft. Bypass patency was assessed in the follow-up period by clinical evaluation, color-flow duplex imaging, or segmental limb pressure measurements.. There was no significant difference in the 30-day operative mortality rate for all AxBF bypasses (11%) and all AxUF bypasses (6%) (p = 0.89 by chi-squared testing). The primary and secondary patency rates for the whole group of bypasses were 80% and 89% at 3 years, respectively (SE < 0.1). Between the AxBF and AxUF groups, there were no significant differences in either primary patency (80% for each group) or secondary patency (91% in AxBFs vs 85% in AxUFs) (SE < 0.1) at 2 years (Wilcoxon rank sum test).. These data show no differences in the patency of externally supported PTFE AxBF and AxUF bypass grafts up to 2 years after implantation.

Topics: Aged; Aged, 80 and over; Anastomosis, Surgical; Aorta; Arteriosclerosis; Aspirin; Axillary Artery; Blood Vessel Prosthesis; Combined Modality Therapy; Female; Femoral Artery; Follow-Up Studies; Graft Occlusion, Vascular; Graft Survival; Humans; Male; Middle Aged; Polytetrafluoroethylene; Prosthesis Design; Reoperation; Thrombectomy; Thrombosis; Time Factors; Vascular Patency; Warfarin

The long-term effects of fish-oil supplementation on haemostatic parameters and bleeding episodes were investigated in patients undergoing coronary artery bypass surgery. They were investigated before and 9 months after the operation. Following randomization postoperatively, 260 patients received 4 g fish-oil concentrate per day, whereas 251 patients comprised the control group. All patients received either aspirin (300 mg/day) or warfarin (international normalized ratio aimed at 2.5-4.2). Compliance was affirmed by determination of serum phospholipid fatty acids. No excess of bleeding episodes could be attributed to the use of fish oil, given in addition to either aspirin or warfarin. The supplementation of fish oil did not affect the bleeding time or plasma levels of beta-thromboglobulin, whereas an increase in the platelet count after the operation was slightly less pronounced in the fish-oil group. Apart from a small increase in PAI-1 antigen of borderline significance, no long-term effects by fish oil on parameters of coagulation and fibrinolysis were seen.

Topics: Aged; Antithrombin III; Arteriosclerosis; Aspirin; Bleeding Time; Coronary Artery Bypass; Coronary Disease; Drug Therapy, Combination; Fatty Acids; Female; Fibrin Fibrinogen Degradation Products; Fish Oils; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Peptide Hydrolases; Phospholipids; Platelet Count; Risk Factors; Treatment Outcome; Triglycerides; Warfarin

HMG CoA reductase inhibitors (or statins), a new class of lipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they more effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease.. Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial with factorial design along with warfarin (1 mg/d) or its placebo. This report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 919 asymptomatic men and women, 40 to 79 years old, with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3-year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the carotid arteries was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups. Among participants not on warfarin, regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was statistically significant (P = .001). A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant (P = .12). Five lovastatin-treated participants suffered major cardiovascular events--coronary heart disease mortality, nonfatal myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P = .04). One lovastatin-treated participant died, compared with eight on lovastatin-placebo (P = .02).. In men and women with moderately elevated LDL cholesterol, lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality. Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins.

Topics: Adult; Aged; Arteriosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Double-Blind Method; Female; Humans; Lovastatin; Male; Middle Aged; Risk Factors; Survival Analysis; Tunica Intima; Tunica Media; Ultrasonography; Warfarin

An NHLBI-sponsored randomized, double-masked, placebo-controlled, multicenter clinical trial is underway to test the efficacy of the lipid-lowering agent lovastatin and/or the antithrombotic agent warfarin in slowing the progression of early carotid atherosclerosis--as defined by ultrasonographic intimal-medial arterial wall thickening--in a high-risk, asymptomatic population consisting of 919 men and women aged 40-79 years with moderately elevated serum LDL-cholesterol. The Asymptomatic Carotid Artery Plaque Study's (ACAPS) factorial design permits evaluation of each of the two treatments alone as well as assessment of the treatments in combination with each other over a 2.5- to 3.0-year treatment period. Randomized participants receive either 20-40 mg/day lovastatin or lovastatin placebo and either 1 mg/day (minidose) warfarin or warfarin placebo. All participants were encouraged to take low-dose (81 mg/day) aspirin. The primary outcome is the ultrasonographic measurement of the mean of maximum intimal-medial thickness (IMT) across up to 12 preselected segments in the carotid arteries. The secondary outcome of the trial measures the single maximum IMT measurement among the same preselected carotid artery segments. This report describes the rationale for ACAPS, its design, and some baseline characteristics of the study population.

Topics: Adult; Aged; Arteriosclerosis; Carotid Artery Diseases; Drug Therapy, Combination; Female; Humans; Lovastatin; Male; Middle Aged; Patient Compliance; Research Design; Risk Factors; Statistics as Topic; Ultrasonography; Warfarin

With the recent increase in the use of antithrombotic therapy, intracerebral hemorrhage (ICH) has been found to be a common complication. We determined whether the use of oral antithrombotic therapy and the patients' preexisting comorbidities were predictive of cerebellar hemorrhage (CH; previously reported to be associated with anticoagulants) as compared to other ICH, and whether antithrombotic therapy affected the clinical severity of CH.. A study of 327 consecutive patients hospitalized in our institute within 3 days after the onset of ICH, including 38 patients with a CH.. CH accounted for 12% of all ICH, 75% of which occurred in patients on warfarin therapy with an international normalized ratio (INR) for prothrombin time >2.5 (p < 0.0001), and 33% of which occurred in patients on ticlopidine therapy (p = 0.017). Warfarin therapy with an INR >2.5 and high blood glucose on admission were independently predictive of CH as compared to other ICH. In addition, previous ischemic stroke (p = 0.002) and heart diseases (p = 0.018) were more prevalent in patients with CH than in those with other ICH. The number of major arteriosclerotic comorbidities and risk factors was also independently predictive of CH risk.. We confirmed that warfarin therapy with an INR >2.5 is associated with CH. Patients with CH frequently had arteriosclerotic comorbidities requiring antithrombotic therapy that can complicate their acute management.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Arteriosclerosis; Aspirin; Blood Glucose; Cerebellar Diseases; Female; Fibrinolytic Agents; Heart Diseases; Humans; Intracranial Hemorrhages; Japan; Male; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stroke; Ticlopidine; Time Factors; Warfarin

Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally.. Male Wistar rats received a high fat diet during 2 months followed by a low dose of streptozotocin to induce diabetes (D). Elastocalcinosis was facilitated by 3 weeks of treatment with warfarin and vitamin K (WVK). We started WVK treatment 1 week (D4WVK) and 4 weeks (D7WVK) after the injection of streptozotocin and in age-matched healthy rats. Measurements of hemodynamic and metabolic parameters, aortic and femoral calcium content, and immunohistochemistry for alkaline phosphatase, osteopontin, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-TGF-beta were performed.. Three weeks of WVK treatment alone did not increase the calcium content in the aorta and femoral arteries. However, in the D7WVK group, femoral calcification, but not aortic calcium content, increased significantly as compared to the WVK group. This response was not observed in the D4WVK group. In femoral arteries, strong immunostaining for alkaline phosphatase and osteopontin was observed in the D7WVK group. TNF-alpha and TGF-beta expressions were mainly localized in the adventitia of arteries from diabetic rats.. We have established a model of accelerated elastocalcinosis in diabetes related to its duration and localized in distal arteries. The modification of local protein expression is also in accordance with clinical data, suggesting that this model could be useful to investigate mechanisms related to this important clinical macrovascular complication of diabetes.

Topics: Alkaline Phosphatase; Animals; Aorta; Arteriosclerosis; Calcinosis; Calcium; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Femoral Artery; Immunohistochemistry; Male; Models, Animal; Osteopontin; Rats; Rats, Wistar; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vitamin K; Warfarin

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Aorta, Thoracic; Arteriosclerosis; Cardiac Catheterization; Embolism, Cholesterol; Humans; Hypertension; Lower Extremity; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Stents; Syndrome; Ultrasonography; Warfarin

Topics: Abdominal Abscess; Anticoagulants; Aortic Diseases; Arterial Occlusive Diseases; Arteriosclerosis; Calcinosis; Conversion Disorder; Diagnostic Errors; Female; Humans; Hypesthesia; Ischemia; Leg; Middle Aged; Muscle Denervation; Paraplegia; Peripheral Nerves; Thrombosis; Tibial Arteries; Tomography, X-Ray Computed; Warfarin

Topics: Anticoagulants; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Atrial Fibrillation; Electric Countershock; Heart Rate; Humans; Risk Factors; Stroke; Thromboembolism; Warfarin

Severe aortic plaques seen on transesophageal echocardiography (TEE) are a high-risk cause of stroke and peripheral embolization. Evidence to guide therapy is lacking. Retrospective information was obtained regarding the occurrence of embolic events (stroke, transient ischemic attacks, or peripheral emboli) in 519 patients with severe thoracic aortic plaque seen on TEE since 1988. Treatment with statins, warfarin, or antiplatelet medications was noted. Treatment was not randomized. In a matched-paired analysis, each patient taking each class of therapy was matched for age, gender, previous embolic event, hypertension, diabetes, congestive failure, and atrial fibrillation to someone not taking that medication. Multivariate analysis was also performed. An embolic event occurred in 111 patients (21%). Multivariate analysis showed that statin use was independently protective against recurrent events (p = 0.0001). Matched analysis also showed a protective effect of statins (p = 0.0004; absolute risk reduction 17%, relative risk reduction 59%, number needed to treat [n = 6]). No protective effect was found for warfarin or antiplatelet drugs. The odds ratio for embolic events was 0.3 (95% confidence interval [CI] 0.2 to 0.6) for statin therapy, 0.7 (95% CI 0.4 to 1.2) for warfarin, and 1.4 (95% CI 0.8 to 2.4) for antiplatelet agents. Thus, there is a protective effect of statin therapy, and no significant benefit of warfarin or antiplatelet drugs on the incidence of stroke and other embolic events in patients with severe thoracic aortic plaque on TEE.

Topics: Aged; Anticoagulants; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Echocardiography, Transesophageal; Embolism; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Longitudinal Studies; Male; Multivariate Analysis; Odds Ratio; Platelet Aggregation Inhibitors; Retrospective Studies; Stroke; Treatment Outcome; Warfarin

Numerous randomized trials document the value of antithrombotic agents for the treatment of cardiovascular disease (CVD). Although antithrombotic agents are often prescribed at hospital discharge after CVD-related events, much less is known about the ongoing use of such agents.. We examined the use of oral antithrombotic agents among a random sample of 2500 persons with atherosclerotic CVD who were enrolled in Kaiser Permanente Northwest Region, a not-for-profit group-model health maintenance organization. Study subjects were identified based on a diagnosis of coronary heart disease, ischemic stroke or transient ischemic attack, or peripheral arterial disease in outpatient problem lists, visit records, and hospital discharge abstracts. Use of prescription antithrombotic agents was identified from pharmacy dispensing records. Regular use of aspirin, recall of aspirin advice and education, and other patient characteristics were ascertained by mail survey.. Among the 1844 subjects who returned the survey and answered the question regarding aspirin use, 84% were using either aspirin (72%) or a prescription antithrombotic agent (12%), typically warfarin sodium. Antithrombotic therapy was relatively underused in persons with peripheral arterial disease (75% used an antithrombotic agent and 62% used aspirin). Use of antithrombotic agents, including aspirin, did not differ by age but was higher among men (87%, 76%) than women (81%, 67%). Nearly all subjects reported having received aspirin education (94%) or advice (81%); recall of education or advice was associated with a dramatically higher likelihood of using antithrombotic agents. To a lesser extent, so was contact with a cardiologist or vascular surgeon during the prior year.. High rates of use of antithrombotic agents can be achieved among persons with CVD in integrated not-for-profit health systems with mechanisms in place to encourage such use, including guidelines, messages to clinicians, nurse care management, alerts and routines embedded in electronic medical records, and direct mailings to patients. Continued efforts should be made in all settings to optimize the use of antithrombotic therapy among persons at an elevated risk of atherothrombotic events.

Topics: Administration, Oral; Aged; Arteriosclerosis; Aspirin; Comorbidity; Coronary Artery Disease; Drug Utilization; Female; Fibrinolytic Agents; Health Maintenance Organizations; Humans; Male; Middle Aged; Socioeconomic Factors; Surveys and Questionnaires; United States; Warfarin

Thrombin has been proposed to play a key role in the development of atherosclerosis, both by promoting fibrin deposition into the atherosclerotic vessel wall and also by signalling through thrombin receptors. Unfortunately, mice homozygous for a deletion of the prothrombin gene (FII) die in utero, making a direct assessment of the role of thrombin during atherogenesis difficult. We have assessed the contribution of thrombin-dependent processes to vascular lipid lesion formation in the atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice by inhibiting thrombin generation with warfarin. ApoE-/- mice were treated with warfarin at a dose that increased the prothrombin time (PT) more than 10-fold (250-375 microg/kg body weight/day) for 12 weeks from the age of 12 weeks onwards. The extent and composition of the vascular lipid lesions that developed were assessed using oil red O to measure neutral lipid in the vessel wall and quantitative immunofluoresence to measure fibrin(ogen) levels as well as macrophage and smooth muscle cell numbers. Mice treated with warfarin developed lesions both in the aortic sinus and the descending aorta to the same degree as mice receiving no treatment (28,351+/-350 microm2/mouse treated with warfarin versus 27,952+/-750 micro2/control mouse; P = .86). However, the amount of fibrin(ogen) deposited in the vessel wall was decreased by more than 60% (34+/-11 arbitrary units in warfarin treated mice versus 92+/-11 arbitrary units in control mice; P < .01). Staining of macrophage and for smooth muscle cell markers was unaltered by treatment with warfarin. We conclude that suppressing thrombin generation does not alter the development of vascular lipid lesions in mice with a severe disorder of lipid metabolism, despite a marked reduction in fibrin(ogen) deposition.

Topics: Animals; Anticoagulants; Aorta; Apolipoproteins E; Arteriosclerosis; Depression, Chemical; Disease Models, Animal; Fibrin; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular; Prothrombin Time; Thrombin; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Contraindications; Fingers; Foot Diseases; Hemorrhage; Humans; Phenindione; Toes; Warfarin

Although essential thrombocythemia (ET) is usually primarily considered a disorder of middle age, it has been observed in children and young adults. However, the real risk for thrombosis in these patients has not been clearly established.. Prospective analysis of consecutive patients younger than 40 at the time of the diagnosis of ET and followed in our department between 1980 and 1998.. Sixty-eight patients (28 males and 40 females, median follow-up 99.14 months) affected by ET diagnosed in agreement with the Polycythemia Vera Study Group criteria.. Asymptomatic ET patients were not treated. In contrast, patients with associated atherosclerotic risk factors, microvascular disturbances, or a previous major arterial thrombosis were given acetyl salicylic acid (ASA 100 mg/day). Only patients with major thrombotic complications and a platelet count > 1,000 x 10(9)/L received cytoreductive therapy.. (1) to evaluate thrombotic complications in young patients with ET, (2) to relate thrombotic risk to the presence of general atherosclerotic risk factors, and (3) to adopt treatment, and (4) to report the outcome of the pregnancies monitored in our population.. Fifteen patients had major thrombosis, 11 of which were the presenting features of ET. No rethrombosis has been observed. Only one patient with thrombotic complications was under efficient treatment. Atherosclerotic risk factors are more common in patients with major arterial thrombosis than in asymptomatic subjects. Thirteen normal babies were delivered out of 16 pregnancies, 6 of the pregnant women were on ASA therapy.. Most thrombosis in young ET patients occurred at the time of the diagnosis, and venous thrombotic events represent one-third of total thrombosis. Cardiovascular risk factors seem to be concurrent stimuli for arterial thrombosis in ET. The thrombotic complication rate was 2.6/100 patients/year ASA reduces microvascular disturbances, thrombosis, and rethrombosis and possibly reduces obstetric complications in women with ET.

Topics: Acute Disease; Adult; Age Factors; Arteriosclerosis; Aspirin; Busulfan; Cohort Studies; Disease-Free Survival; Female; Follow-Up Studies; Hemorrhage; Heparin; Humans; Hydroxyurea; Leukemia; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Outcome; Primary Myelofibrosis; Prospective Studies; Risk Factors; Splenectomy; Thrombocythemia, Essential; Venous Thrombosis; Warfarin

To evaluate in a group of seriously diseased patients with nonreconstructable chronic critical leg ischemia (CLI), treated by a combination of i.v. hydroxyethylrutosides (HR)* and oral anticoagulation (AC) by warfarin, the short-term effects on the cutaneous microvascular blood perfusion of the soles of feet and especially the long-term clinical outcome in terms of amputation and death.. A retrospective comparison between two groups of patients, HR + AC and a comparable reference group, fulfilling the same inclusion and exclusion criteria corresponding to the definition of CLI according to the Second European Consensus Document (1991). Clinical follow-up in both groups was made after 1, 3, 6, 12, and 24 months.. Patients were examined at university departments of clinical physiology with special interest in peripheral vascular disease, in cooperation with colleagues at university departments of surgery, internal medicine and dermatology of Karolinska Hospital, Södersjukhuset and Huddinge Hospital.. A total of seventy patients with CLI according to the definition of the Second European Consensus Document, 1991, ie, besides severe rest pain or ischemic lesions also a toe blood pressure < 30 mg Hg. Group with HR + anticoagulation (AC): 42 patients (19 diabetics, 23 nondiabetics). Reference group: 28 patients (18 diabetics, 10 nondiabetics). For distribution of age and toe blood pressure at baseline, see Table I.. Therapy group: besides ordinary standard therapy, daily HR infusions for a mean period of 3.6 weeks + oral anticoagulation continued to the end of the study at 24 months. A comparable reference group on the same basic therapy but without the combination HR + AC. PARAMETERS IN EVALUATION: Short-term parameters: clinical data, skin temperature, and fluorescein imaging. Long-term outcome: amputation or death.. Short-term and long-term results with HR + AC indicated that patients with severe CLI and very poor prognosis benefited in terms of survival and limb salvage from initial therapy with HR infusion combined with long-term oral anticoagulation. Results of this combined treatment seem at least comparable with those with i.v. prostacyclin analogies.

Topics: Administration, Oral; Aged; Amputation, Surgical; Anticoagulants; Arteriosclerosis; Blood Pressure; Cardiovascular Agents; Contrast Media; Diabetic Angiopathies; Drug Therapy, Combination; Fluorescein; Follow-Up Studies; Foot; Humans; Hydroxyethylrutoside; Infusions, Intravenous; Ischemia; Leg; Longitudinal Studies; Microcirculation; Prognosis; Retrospective Studies; Skin Temperature; Survival Rate; Treatment Outcome; Warfarin

We sought to determine the influence of plaque morphology and warfarin anticoagulation on the risk of recurrent emboli in patients with mobile aortic atheroma.. An epidemiologic link between aortic atheroma and systemic emboli has been described both in pathologic and transesophageal studies. Likewise, a few studies have found an increased incidence of recurrent emboli in these patients. The therapeutic implications of these findings has not been studied.. Thirty-one patients presenting with a systemic embolic event and found to have mobile aortic atheroma were studied. The height, width and area of both immobile and mobile portions of atheroma were quantitated. The dimensions of the mobile component was used to define three groups: small, intermediate and large mobile atheroma. The patients were followed up by means of telephone interview and clinical records, with emphasis on anticoagulant use and recurrent embolic or vascular events.. Patients not receiving warfarin had a higher incidence of vascular events (45% vs. 5%, p = 0.006). Stroke occurred in 27% of these patients and in none of those treated with warfarin. The annual incidence of stroke in patients not taking warfarin was 0.32. Myocardial infarction occurred in 18% of patients also in this group. Taken together, the risk of myocardial infarction or stroke was significantly increased in this group (p = 0.001). Forty-seven percent of patients with small, mobile atheroma did not receive warfarin. Recurrent stroke occurred in 38% of these patients, representing an annual incidence of 0.61. There were no strokes in patients with small, mobile atheroma treated with warfarin (p = 0.04). Likewise, none of the patients with intermediate or large mobile atheroma had a stroke during follow-up. Only three of these patients had not been taking warfarin.. Patients presenting with systemic emboli and found to have mobile aortic atheroma on transesophageal echocardiography have a high incidence of recurrent vascular events. Warfarin is efficacious in preventing stroke in this population. The dimension of the mobile component of atheroma should not be used to determine the need for anticoagulation.

Topics: Aged; Anticoagulants; Aortic Diseases; Arteriosclerosis; Cerebrovascular Disorders; Coronary Thrombosis; Echocardiography, Transesophageal; Female; Humans; Male; Middle Aged; Recurrence; Treatment Outcome; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Humans; Warfarin

Activated protein C resistance caused by factor V Leiden is an important thrombophilia disorder which predisposes to venous thromboembolism. Some studies also suggest a role in the pathogenesis of arterial thrombosis and atherosclerosis. The authors have investigated the prevalence of activated protein C resistance and factor V Leiden in a series of 45 patients with peripheral vascular disease. Twelve patients were receiving warfarin. The activated protein C resistance ratios were significantly lower in the group of 33 non-warfarinized patients with peripheral vascular disease (median 2.82 (range 1.36-3.83)) compared with 33 age- and sex-matched controls (median 2.97 range 2.24-4.11); P<0.005; Wilcoxon rank sum). Eight patients (24%) had activated protein C resistance (ratio <2.2). The prevalence of factor V Leiden in patients with peripheral vascular disease was 17.8% (8/45). This is significantly increased compared with the local population and UK published frequency of 3.5% for this genotype. The presence of factor V Leiden did not affect the late outcome of arterial reconstructive surgery in terms of graft patency (P=0.5, Fisher's Exact test).

Topics: Aged; Arteriosclerosis; Blood Coagulation Tests; Enzyme Activation; Factor V; Female; Graft Occlusion, Vascular; Humans; Ischemia; Leg; Male; Middle Aged; Protein C; Reoperation; Risk Factors; Warfarin

Atherosclerotic lesions of the aortic arch are potential sources of arterial embolism. Mobile thrombi in the aortic arch in young patients without diffuse atherosclerosis have been reported recently, but such cases remain exceptional. We describe a series of young patients with unexplained arterial embolism in whom transesophageal echocardiography detected mobile aortic arch thromboses.. Transesophageal echocardiography files collected between 1991 and 1995 in French academic cardiology centers were reviewed to identify patients who fulfilled the following criteria: (1) an arterial embolic event in the preceding weeks; (2) a mobile pedunculated aortic arch thrombosis, defined as an echogenic mass protruding into the lumen of the aorta and inserted on the aortic arch; and (3) absence of obvious diffuse aortic atherosclerosis or of aortic debris on transesophageal echocardiography. Twenty-three cases were identified from 27 855 examinations. Thromboses were located on the horizontal aorta (n = 4), near the ostium of the left subclavian artery (n = 5), or on the concavity of the posterior segment of the aortic arch (in the isthmus) (n = 14). The insertion site was a small atherosclerotic plaque in 21 patients. The remaining aortic wall always appeared normal or mildly atherosclerotic. The mean age of the patients was 45 +/- 8.4 years (range, 26 to 61 years). All patients were treated with intravenous heparin after the diagnosis of aortic arch thrombosis, and surgical removal of the thrombosis was performed in 10 patients in whom histological examination confirmed an atherosclerotic process at the site of insertion of the thrombosis. The prognosis was mainly influenced by embolic events.. Thromboses of the aortic arch appear to be a variant form of aortic atherosclerotic disease associated with arterial embolism in young patients.

Topics: Adult; Aorta, Thoracic; Arteriosclerosis; Aspirin; Blood Coagulation Tests; Diabetes Complications; Echocardiography, Transesophageal; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Smoking; Thrombectomy; Thrombosis; Warfarin

Stroke from surgically inaccessible intracranial atherostenosis remains a formidable clinical challenge. While antithrombotic or antiplatelet therapy may prevent distal embolism, there is no effective program for plaque stabilization preventing progression of atherosclerotic stenosis. In patients with isolated circulations (single vertebral with absent posterior communicating arteries, single carotid with contralateral internal carotid artery occlusion, or single carotid with an absent anterior communicating artery), occlusion of the stenotic vessel may produce a low flow-mediated stroke. Fifteen patients with atherosclerotic intracranial stenoses were treated by balloon angioplasty after medical therapy with warfarin failed. Treated territories included the distal internal carotid, proximal middle cerebral, distal vertebral, and basilar arteries. Dilation was successful in all vessels, with residual stenoses averaging less than 30%. Two complications included one paramedian pontine stroke and a single vessel rupture that proved fatal. There was no recurrence of transient ischemic attacks and no restenosis at the angioplasty site over a follow-up period of more than 24 months. In this small series, balloon angioplasty of intracranial vessels provided a therapeutic option for secondary stroke prevention in highly selected patients. Further studies will be necessary to establish the efficacy and safety of endovascular treatment in larger series.

Topics: Adult; Aged; Angioplasty, Balloon; Anticoagulants; Arteriosclerosis; Basilar Artery; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Cerebral Arteries; Cerebrovascular Disorders; Disease Progression; Embolism; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Regional Blood Flow; Rupture; Vertebral Artery; Warfarin

Thrombosis can occur on the venous or the arterial side of the circulation. Each has different causes, requires a different diagnostic workup, and responds to different therapies. Venous thrombosis may be situational, but may also reflect inherited or acquired anticoagulation defects. Arterial thrombosis usually results from abnormalities in the blood vessel wall--most often atherosclerosis.

Topics: Adult; Algorithms; Anticoagulants; Arteriosclerosis; Blood Coagulation Disorders; Diagnosis, Differential; Factor V; Heparin; Humans; Male; Partial Thromboplastin Time; Recurrence; Thrombophlebitis; Warfarin

Topics: Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; Blue Toe Syndrome; Cohort Studies; Embolism, Cholesterol; Heparin; Humans; Ischemic Attack, Transient; Warfarin

Topics: Aged; Aortic Aneurysm, Abdominal; Arteriosclerosis; Cholesterol; Embolism; Humans; Male; Skin; Toes; Warfarin

Warfarin sodium (Coumadin) has been used as an effective anticoagulating agent in human medicine for many years, although careful monitoring of its effects are necessary to avoid excessive anticoagulation. Previous experience with this drug for chronic anticoagulation therapy in miniature swine has been limited. The effect of warfarin sodium was studied by measuring prothrombin time in twelve 8-month-old Hanford miniature swine. The pigs had been fed a high-cholesterol diet and had undergone a prior coronary artery abrasion procedure for development of an atherosclerotic coronary disease model. Atherosclerosis was induced by feeding a high-cholesterol diet. Baseline prothrombin time ranged from 12.8 to 15.0 s (13.7 s mean). Prothrombin time was determined daily for the first 5 days of treatment and at least twice weekly thereafter until the animals were sacrificed. Animals received warfarin for 37-41 days. Prothrombin time could be increased 33-50% by once daily oral administration of warfarin 0.04-0.08 mg/kg. Oral administration of more than 0.08 mg/kg as a maintenance dose resulted in the death of two pigs. Most animals responded well to 0.08 mg/kg for the first 3 days of treatment followed by a maintenance dose of 0.06 mg/kg. Dosage was adjusted periodically when prothrombin times exceeded 50% above baseline. It is our experience that monitoring prothrombin time at least twice weekly and adjusting the maintenance dose can eliminate death losses due to warfarin intoxication.

Topics: Animals; Arteriosclerosis; Cholesterol, Dietary; Diet, Atherogenic; Disease Susceptibility; Hemorrhagic Disorders; Male; Prothrombin Time; Swine; Swine, Miniature; Warfarin

Topics: Arteriosclerosis; Biopsy; Dipyridamole; Graft Rejection; Heparin; Humans; Kidney; Kidney Glomerulus; Kidney Transplantation; Plasma Exchange; Prospective Studies; Time Factors; Warfarin

The "purple toes syndrome" is a rare complication of oral anticoagulant therapy. Four patients who presented with "purple toes syndrome" several weeks after warfarin therapy was initiated are described. The diagnosis of cholesterol microembolization was made by biopsy in three cases. Malignant hypertension and renal failure developed in two patients who died within three to six months of onset of purple toes. Postmortem examination in one of these patients showed widespread cholesterol microembolization. Renal failure has not developed in the other two patients, who are doing well. These biopsy and autopsy results suggest that the warfarin-related "purple toes syndrome" is due to cholesterol microembolization.

Topics: Aged; Arteriosclerosis; Cholesterol; Color; Embolism; Female; Humans; Male; Middle Aged; Regional Blood Flow; Syndrome; Toes; Warfarin

Topics: Aged; Arteriosclerosis; Cholesterol; Female; Humans; Male; Platelet Aggregation; Thromboembolism; Ticlopidine; Warfarin

Interventional angiographic techniques are of increasing importance in the management of arteriosclerosis and its complications. Two areas of particular interest are the treatment of focal arterial stenoses by percutaneous transluminal angioplasty and the treatment of arterial thromboemboli with selective infusion of thrombolytic agents. The administration of multiple drugs, in various combinations, is a critical factor in the success of these interventions. To effectively use this new pharmacoangiography, it is important to understand both the pathophysiology of the atherosclerotic or thrombotic process being treated and the actions of the drugs used. Preserving the effect of angioplasty relies on preventing thrombus formation and preventing recurrence of the atherosclerotic obstruction. Heparin during the procedure is clearly useful for the former, and aspirin in small doses and other antiplatelet medications are indicated for the latter. The precise utility of long-term anticoagulation, of low molecular weight dextran, and of various antiplatelet regimens remains to be proven. The theoretical importance of these medications in improving long-term patency rests on the effects they have on platelet and vessel wall prostaglandins, on intimal smooth muscle cell proliferation, and on the thrombogenicity of injured arterial intima. Fibrinolytic therapy, with streptokinase and urokinase, has been used for many years. Selective intraarterial use, however, is a new and promising application. Intracoronary streptokinase infusion during acute myocardial ischemia appears to prevent or limit infarction in certain patients. Peripheral use for acute arterial occlusion, either in native vessels or in grafts, is an area of great promise. Key considerations are thrombus age, size, and location, and the status of the arterial flow proximal and distal to the obstruction.

Topics: Angioplasty, Balloon; Anticoagulants; Arteriosclerosis; Aspirin; Blood Platelets; Dextrans; Dipyridamole; Heparin; Humans; Middle Aged; Prostaglandins; Streptokinase; Sulfinpyrazone; Thromboembolism; Urokinase-Type Plasminogen Activator; Warfarin

Arterial thrombosis and venous thrombosis differ in pathogenesis, morphology, and response to antithrombotic therapy. Antiplatelet therapy usually is aimed at arterial thrombi, in whose formation platelet-mediated reactions predominate, while anticoagulant therapy is effective against venous thrombi, in whose formation coagulation predominates.

Topics: Anticoagulants; Arteries; Arteriosclerosis; Aspirin; Blood Coagulation; Blood Coagulation Factors; Dipyridamole; Fibrinolytic Agents; Humans; Platelet Adhesiveness; Sulfinpyrazone; Thrombophlebitis; Thrombosis; Urokinase-Type Plasminogen Activator; Veins; Warfarin

Several members of a family living on the west coast of Scotland and on one of the islands off the coast had serious thrombotic disease. The plasma antithrombin III (ATIII) concentrations were measured by both functional and immunological assay in all available members of the family. Concentrations were 25% to 66% of normal in 12 people, including all seven with thrombotic disease. The inheritance pattern was characteristic of an autosomal dominant disorder. Thrombotic disease generally affected the leg, mesenteric, and axillary veins, although one man who had died before the study began had had severe arterial atheroma. In women the first thrombotic symptoms usually occurred during pregnancy. None of these patients have developed thrombotic symptoms until they were at least 18, so four younger members of the family who have ATIII deficiency but no thrombotic disease may eventually develop symptoms.

Topics: Adolescent; Adult; Aged; Antithrombins; Arteriosclerosis; Child; Female; Humans; Male; Middle Aged; Pedigree; Thrombophlebitis; Thrombosis; Warfarin

Patients with transient ischemic attacks (TIAs) due to atherosclerosis were studied by aortocranial arteriography. Onset of TIAs was before age 55 in 24% and between 55 and 64 in 47%. Men exceeded women by two to one. Of 160 patients, 77 were treated medically and 82 surgically. Five died in the immediate postoperative period. In the survivors, mortality has been the same in the medically and surgically managed groups. For patients with multiple lesions, surgical reconstruction of the carotid arteries was associated with very high surgical risk. In the medically treated group, anticoagulant therapy reduced the frequency of TIAs, but did not appear to protect patients from stroke. Mortality was 23% at four years, 57% of deaths being attributable to myocardial infarction and 38% to stroke.

Topics: Adult; Aged; Arteriosclerosis; Cerebrovascular Disorders; Diabetes Complications; Endarterectomy; Female; Follow-Up Studies; Heart Diseases; Humans; Hypertension; Ischemic Attack, Transient; Male; Middle Aged; Prognosis; Prospective Studies; Radiography; Risk; Warfarin

Topics: Adult; Aged; Arteriosclerosis; Aspirin; Blood Cell Count; Blood Platelets; Dipyridamole; Drug Synergism; Female; Fibrinogen; Heparin; Humans; Male; Middle Aged; Plasminogen; Thromboembolism; Thrombophlebitis; Warfarin

Topics: Aged; Aminosalicylic Acids; Arteriosclerosis; Drug Synergism; Humans; Male; Warfarin

Topics: Adult; Aged; Anticoagulants; Arteries; Arteriosclerosis; Coronary Disease; Ethyl Biscoumacetate; Female; Follow-Up Studies; Humans; Leg; Long-Term Care; Male; Middle Aged; Phenindione; Prognosis; Thrombosis; Vascular Diseases; Warfarin

Topics: Acetates; Adenosine Diphosphate; Animals; Anti-Inflammatory Agents; Arteriosclerosis; Arthritis, Rheumatoid; Blood Coagulation; Collagen; Coumarins; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Ethyl Biscoumacetate; Fibrinolysis; Humans; In Vitro Techniques; Methods; Phenylbutazone; Platelet Adhesiveness; Pyrazoles; Rats; Thrombophlebitis; Warfarin

Topics: Aged; Anticoagulants; Arteriosclerosis; Arthritis; Breast Diseases; Female; Gangrene; Humans; Hypertension; Mastectomy; Middle Aged; Necrosis; Penicillins; Postoperative Complications; Thrombophlebitis; Warfarin

Topics: Aged; Angina Pectoris; Anticoagulants; Arteriosclerosis; Coronary Disease; Humans; Male; Middle Aged; Myocardial Infarction; Recurrence; Warfarin

Topics: Arteriosclerosis; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Angiography; Cerebrovascular Disorders; Dextrans; Hematologic Diseases; Heparin; Humans; Infarction; Injections, Intravenous; Ischemic Attack, Transient; Papaverine; Subclavian Steal Syndrome; Vertebral Artery; Warfarin

Topics: Arteriosclerosis; Coronary Disease; Humans; Middle Aged; Thromboembolism; Time Factors; Warfarin; Washington

The outcome of 185 consecutive autogenous vein bypass grafts for femoro-popliteal occlusions carried out between January 1962 and June 1968 has been reviewed. One patient died at operation and 21 late deaths have occurred since. The overall five-year patency was 61.5%, but was much lower when the popliteal-tibial runoff arteries were diseased. Distal anastomosis of the graft to the popliteal artery below the level of the knee joint also impaired the results, and if this was performed with a graft of minimal diameter less than 5 mm. sustained patency was obtained in only a quarter of the limbs. Nevertheless, where major amputation was imminent owing to advanced ischaemia three out of four limbs were salvaged.

Topics: Adult; Aged; Arteriosclerosis; Electrocardiography; Female; Femoral Artery; Follow-Up Studies; Humans; Ischemia; Male; Middle Aged; Phenindione; Popliteal Artery; Postoperative Complications; Transplantation, Autologous; Vascular Diseases; Veins; Warfarin

Topics: Adult; Aged; Amputation, Surgical; Arteriosclerosis; Diabetic Angiopathies; Female; Femoral Artery; Follow-Up Studies; Heparin; Humans; Male; Methods; Middle Aged; Postoperative Care; Transplantation, Autologous; Veins; 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: Acute Kidney Injury; Arteriosclerosis; Cholesterol; Embolism, Fat; Gangrene; Humans; Hypertension; Male; Middle Aged; Pancreatitis; Toes; Warfarin

Topics: Angina Pectoris; Anticoagulants; Arteriosclerosis; Family Practice; General Practice; Intracranial Embolism; Intracranial Embolism and Thrombosis; Mortality; Myocardial Infarction; Private Practice; Prothrombin Time; Statistics as Topic; Thrombosis; Toxicology; Warfarin

Topics: Arteriosclerosis; Atrial Fibrillation; Cerebrovascular Disorders; Coronary Disease; Dicumarol; Diet; Diet Therapy; Family Practice; General Practice; Humans; Intracranial Embolism; Intracranial Embolism and Thrombosis; Myocardial Infarction; Prothrombin Time; Thrombosis; Vitamin K; Warfarin

Topics: Angina Pectoris; Anticoagulants; Arteriosclerosis; Blood Coagulation Tests; Drug Therapy; Embolism; Family Practice; General Practice; Myocardial Infarction; Office Management; Prothrombin Time; Rheumatic Heart Disease; Thrombosis; Toxicology; Warfarin

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

Topics: Arteriosclerosis; Biomedical Research; Blood Chemical Analysis; Brain Diseases; Cerebrovascular Disorders; Coronary Disease; Enzyme Inhibitors; Fats; Hydrocortisone; Hypertension; Myocardial Infarction; Pharmacology; Physiology; Rabbits; Research; Thrombin; Warfarin

Topics: Anticoagulants; Arteriosclerosis; Fibrin; Humans; Thrombosis; Warfarin