warfarin and Angina--Unstable

This focused update addresses the use of the newly approved oral antiplatelet agents, prasugrel and ticagrelor, for the management of patients with UA/NSTEMI.

Topics: Adenosine; Administration, Oral; Angina, Unstable; Anticoagulants; Evidence-Based Medicine; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Treatment Outcome; Warfarin

Topics: Angina, Unstable; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Brain Ischemia; Clinical Trials as Topic; Coumarins; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Forecasting; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Morpholines; Myocardial Infarction; Peptide Fragments; Polysaccharides; Prothrombin; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Thrombosis; Warfarin

In patients recovering from acute coronary syndromes (ACS) the role of oral anticoagulation (and its intensity) in addition to aspirin remains controversial. We conducted a specific meta-analysis of randomized trials comparing aspirin plus warfarin (A+W) with aspirin alone in such patients.. MEDLINE and Cochrane databases yielded 14 (of 148 potentially relevant) articles enrolling 25 307 patients. Follow-up ranged from 3 months to 5 years. Irrespective of International normalized ratio (INR), A+W did not significantly affect the risk of major adverse events (MAE: all cause death, non-fatal myocardial infarction, and non-fatal thrombo-embolic stroke) when compared with aspirin alone [OR 0.96 (0.90-1.03), P=0.30], but increased the risk of major bleeds (MB): OR 1.77 (1.47-2.13), P<0.00001. However, in studies with INR of 2-3, A+W was associated with a significant reduction of MAE [OR 0.73 (0.63-0.84), P<0.0001, number needed to treat to avoid one MAE=33], albeit at an increased risk of MB [OR 2.32 (1.63-3.29), P<0.00001; number needed to harm by causing one MB=100]. In both analyses, intracranial bleeding was not significantly increased by A+W when compared with aspirin alone.. For patients recovering from ACS, a combined strategy of A+W at INR values of 2-3 doubles the risk of MB, but is nonetheless superior to aspirin alone in preventing MAE. Whether this combined regimen is also superior to a 'double' anti-platelet strategy or to newer evolving treatments warrants further investigation.

Topics: Angina, Unstable; Anticoagulants; Aspirin; Drug Therapy, Combination; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome; Warfarin

Topics: Angina, Unstable; Aspirin; Cardiac Catheterization; Clopidogrel; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Ticlopidine; Warfarin

We reviewed the efficacy and safety of combination antithrombotic therapy with aspirin plus warfarin versus aspirin alone in patients with atherosclerotic heart disease. We performed a comprehensive MEDLINE search of English-language reports published between 1966 and 2002 and search of references and relevant papers. Only clinical research studies on primary or secondary prevention of cardiovascular events in patients at high risk for coronary artery disease or patients experiencing unstable angina or myocardial infarction were included. Despite daily aspirin treatment, many patients break through aspirin treatment and experience cardiovascular events. Individuals at high risk for coronary disease or with established disease benefit from combination therapy with aspirin plus warfarin, if compliance with warfarin is greater than 70% and the target international normalized ratio (INR) of 2.0-2.5 is achieved. Combination therapy within these parameters leads to a 29-45% reduction in the risk of death, reinfarction and/or ischemic stroke. There is a significant increase in the rate of minor and a slight increase in the rate of major bleeding with combination therapy. Other potential indications for combination therapy include myocardial infarction associated with acute left ventricular aneurysm or significant left ventricular systolic dysfunction. In spite of reluctance to use oral anticoagulants, several large, randomized clinical trials support combination therapy with aspirin plus warfarin (INR, 2.0-2.5) in high-risk patients with atherosclerotic heart disease. Combination therapy increases the risk of minor and major bleeding, but not intracranial bleeding.

Topics: Angina, Unstable; Anticoagulants; Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Primary Prevention; Randomized Controlled Trials as Topic; Stroke; Thrombolytic Therapy; Warfarin

Topics: Angina, Unstable; Aspirin; Clopidogrel; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Ticlopidine; Warfarin

Topics: Angina, Unstable; Aspirin; Cardiac Catheterization; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Ticlopidine; Warfarin

Acute coronary syndromes (unstable angina and acute myocardial infarction) are generally caused by thrombosis over a disrupted atherosclerotic plaque. During the acute phase, antithrombotic therapy (including aspirin and heparin) has been shown to reduce the risk of death or myocardial infarction (MI). The purpose of this review is to examine the high-risk period for clinical thrombotic events that extends for several weeks after presentation and to review the treatments aimed at reducing these events.. More than half of clinical events reported during the first month occur after the first 3 to 5 days that comprise the standard in-hospital treatment period. Several different antithrombotic approaches have been tested, including longer duration of antiplatelet therapy, anticoagulant treatment, and oral glycoprotein (GP) IIb/IIIa inhibitors. Aspirin is effective at reducing risk, and clopidogrel provides additional benefit, as does dalteparin for at least the first month. Warfarin in addition to aspirin, while generally disappointing, has not been adequately tested at higher doses. Oral GP IIb/IIIa inhibitors cause a paradoxic increased risk of death for unclear reasons.. Further reduction of risk during the weeks after presentation with acute coronary syndromes remains an important therapeutic goal.

Topics: Angina, Unstable; Aspirin; Clopidogrel; Coronary Thrombosis; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Thrombolytic Therapy; Ticlopidine; Time Factors; Warfarin

The goal of anticoagulant therapy in unstable angina is to prevent progression of a subocclusive coronary thrombus to complete occlusion of the coronary artery, thereby preventing myocardial infarction and death. Although these have been many advances in therapy with anticoagulants, considerable morbidity and mortality remains. Also, although combination therapy with potent novel anticoagulants and antiplatelet agents may be an alternative strategy, this needs to be balanced against the risks of hemorrhagic complications. More precise and biologically relevant methods of monitoring anticoagulant effect, along with appropriately modified doses given in combination offers promise.

Topics: Angina, Unstable; Anticoagulants; Antithrombins; Arginine; Clinical Trials as Topic; Coronary Thrombosis; Disease Progression; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Warfarin

In the medical literature reports are accumulating a number of case reports suggesting the potential efficacy and safety of the combination of low-dose aspirin and warfarin to improve the efficacy of antithrombotic therapy in several clinical conditions, ranging from unstable angina to myocardial infarction. The advantages deriving from such a combination have to be considered together with its hemorrhagic risk. Thus the efficacy of such a treatment has to be proved by large clinical trials before the use of this potentially dangerous therapy can be transferred into common clinical practice.

Topics: Angina, Unstable; Aspirin; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Thrombolytic Therapy; Warfarin

Acute coronary syndrome is defined as unstable angina or acute myocardial infarction. A discussion on drug treatment of these conditions was arranged by the Norwegian Society of Cardiology and the Department of Pharmacotherapeutics, University of Oslo, soon after preliminary results of the GISSI II study were available. Relatively simple rules were agreed for the use of analgetics, nitrates and fibrinolytic agents. The last are used only after established myocardial injury. Consensus was also reached on the restricted use of calcium antagonists, inotropic agents and diuretics. There was disagreement concerning the dosage of heparin and the exact use of betablockers, aspirin, warfarin, ACE-inhibitors, magnesium and antiarrhythmics.

Topics: Adrenergic beta-Antagonists; Angina, Unstable; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Heparin; Humans; Myocardial Infarction; Norway; Warfarin

Topics: Angina, Unstable; Angioplasty, Balloon; Anticoagulants; Clinical Trials as Topic; Coronary Disease; Heart Ventricles; Heparin; Humans; Myocardial Infarction; Thrombosis; United States; United States Department of Veterans Affairs; Warfarin

There is a modest risk of myocardial infarction (MI) and myocardial ischemic events in patients with atrial fibrillation.. Data from the RE-LY study (Randomized Evaluation of Long-Term Anticoagulation Therapy) were used to report rates of MI, unstable angina, cardiac arrest, and cardiac death and the prespecified net clinical benefit and treatment effects of dabigatran versus warfarin. MI occurred at annual rates of 0.82% and 0.81% with dabigatran 110 or 150 mg BID compared with 0.64% with warfarin (hazard ratio [HR] 1.29, 95% confidence interval [CI] 0.96-1.75, P=0.09 for dabigatran 110 mg; HR 1.27, 95% CI 0.94-1.71, P=0.12 for dabigatran 150 mg). Annual rates of a composite of MI, unstable angina, cardiac arrest, and cardiac death were 3.16% per year with dabigatran 110 mg, 3.33% per year with dabigatran 150 mg, and 3.41% per year with warfarin (HR versus warfarin 0.93, 95% CI 0.80-1.06, P=0.28 for dabigatran 110 mg and HR 0.98, 95% CI 0.85-1.12, P=0.77 for dabigatran 150 mg). Events prespecified as "net clinical benefit" (all strokes, systemic embolism, MI, pulmonary embolism, major bleeding, and all-cause death) occurred at a rate of 7.34% per year with dabigatran 110 mg, 7.11% per year with dabigatran 150 mg, and 7.91% per year with warfarin (HR 0.92, 95% CI 0.84-1.01, P=0.09 for dabigatran 110 mg and HR 0.90, 95% CI 0.82-0.99, P=0.02 for dabigatran 150 mg). The relative effects of dabigatran versus warfarin on myocardial ischemic events were consistent in patients with or without a baseline history of MI or coronary artery disease.. There was a nonsignificant increase in MI with dabigatran compared with warfarin, but other myocardial ischemic events were not increased. Treatment effects of dabigatran were consistent in patients at higher and lower risk of myocardial ischemic events.

Topics: Aged; Aged, 80 and over; Angina, Unstable; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Female; Heart Arrest; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Risk Factors; Single-Blind Method; Warfarin

A different rate and timing of subacute stent thrombosis after percutaneous coronary intervention was reported with various peri-interventional antithrombotic regimens. Next to platelet activation, coagulation triggered by tissue factor (TF) may play a key role in this process. Thirty-one consecutive patients with stable and unstable angina undergoing coronary stenting were randomly assigned to adjunct oral anticoagulation/anti-platelet therapy (coumadin, dipyridamole, aspirin and heparin; n = 16) or adjunct anti-platelet therapy with thienopyridin (ticlopidine, aspirin and heparin; n = 15). Antigen levels of plasma TF, total tissue factor pathway inhibitor (TFPI) and TFPI/ activated factor X (TFPI/FXa) complex were determined before and for up to 6 days after intervention by immunoassay. At baseline, significantly higher levels of plasma TF and TFPI/FXa were found in patients with unstable angina [TF, 161 pg/ml (126-191 pg/ml); TFPI/FXa, 7.8 ng/ml (6.1-9.6 ng/ml)] compared with stable angina [TF, 62 pg/ml (46-82 pg/ml), P < 0.0001; TFPI/FXa, 4.5 ng/ml (3-7.6 ng/ml), P= 0.003]. One hour after intervention, an increase of plasma TF and TFPI/FXa was seen in both treatment groups. In unstable angina patients, plasma levels of TF, TFPI and TFPI/FXa were more efficiently reduced by adjunct ticlopidine therapy compared with adjunct coumadin/dipyridamole. These data suggest reduced release of circulating TF by combined anti-platelet therapy with ticlopidine and aspirin after coronary artery stenting, which may-contribute to the lower incidence of subacute stent thrombosis previously observed.

Topics: Adult; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Coronary Angiography; Coronary Stenosis; Dipyridamole; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Factor Xa; Female; Follow-Up Studies; Hemorrhage; Heparin; Humans; Lipoproteins; Male; Middle Aged; Statistics as Topic; Stents; Thromboplastin; Thrombosis; Ticlopidine; Time Factors; Warfarin

Forty-three patients presenting with unstable angina or myocardial infarction were randomised double blind to warfarin [target international normalised ratio (INR), 2.0 to 2.5] and aspirin (150 mg) daily or placebo plus aspirin (150 mg) daily. Coronary flow was assessed with the thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC). Coronary artery flow was reduced (higher CTFC) at baseline in culprit arteries (mean +/-SD, 37.1+/-15.4 frames) compared to nonculprit arteries (22.5+/-6.7 frames, P<0.0001). In patients with a patent artery at follow-up, coronary flow was unchanged after ten weeks of warfarin and aspirin (-2.0+/-19.9 frames) or aspirin alone (3.8+/-10.4 frames, P = 0.20). Patients randomised to aspirin alone were more likely to progress to total occlusion [aspirin, 7 of 19 (37%) vs. warfarin and aspirin, 1 of 24 (4%); P = 0.01). Higher baseline culprit artery CTFC was also associated with an increased risk of late occlusion [+10 frames; odds ratio (OR), 1.65; 95% CI, 1.01 to 2.33]. Coronary flow remained impaired ten weeks after presentation with myocardial infarction or unstable angina. Combination warfarin and aspirin therapy did not improve flow in vessels that remained patent but did reduce the risk of progression to occlusion.

Topics: Angina, Unstable; Anticoagulants; Aspirin; Blood Flow Velocity; Coronary Angiography; Coronary Circulation; Double-Blind Method; Drug Therapy, Combination; Fibrinolytic Agents; Follow-Up Studies; Humans; Middle Aged; Myocardial Infarction; Placebos; Warfarin

The objectives of the Organization to Assess Strategies for Ischemic Syndromes (OASIS) Pilot Study (phase 2) were (1) to compare the efficacy, safety, and feasibility of recombinant hirudin versus unfractionated heparin as short-term therapy in patients with acute coronary syndromes without ST elevation and (2) to compare the efficacy and safety of long-term therapy with warfarin and aspirin versus standard therapy with aspirin alone in the same patient population. Investigators at 31 Canadian centers randomized 909 patients to receive either medium-dose hirudin, low-dose hirudin, or unfractionated heparin. The incidence of the 7-day primary composite outcome of cardiovascular death, new myocardial infarction (MI), or refractory angina was significantly lower among patients who received hirudin than among those assigned to unfractionated heparin. A subset of these patients was subsequently randomized to long-term, low-intensity (international normalized ratio [INR] < 1.5) or moderate-intensity (INR 2-2.5) anticoagulant treatment with warfarin or to standard therapy. In this substudy, promising results were observed in favor of moderate-intensity warfarin. These findings provided the rationale for the design and conduct of the large-scale, phase III OASIS-2 trial.

Topics: Acute Disease; Aged; Angina, Unstable; Anticoagulants; Aspirin; Canada; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Feasibility Studies; Female; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Pilot Projects; Recombinant Proteins; Recurrence; Registries; Treatment Outcome; Warfarin

We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction.. Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial.. We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome.. On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology.. In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.

Topics: Angina, Unstable; Anticoagulants; Cardiac Output, Low; Cardiovascular Diseases; Cause of Death; Cohort Studies; Female; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Ventricular Dysfunction, Left; Warfarin

Patients with acute ischemic syndromes (AIS) suffer high rates of recurrent ischemic events despite aspirin treatment. Long-term therapy with oral anticoagulants in addition to aspirin may reduce this risk. We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies.. In phase 1, after the cessation of 3 days of intravenous antithrombotic therapy, 309 patients were randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months that produced a mean international normalized ratio (INR) of 1.5+/-0.6 or to standard therapy. Eighty-seven percent of patients received aspirin in both groups. The rates of cardiovascular (CV) death, new myocardial infarction (MI), and refractory angina at 6 months were 6.5% in the warfarin group and 3.9% in the standard therapy group (relative risk [RR], 1. 66; 95% CI, 0.62 to 4.44; P=0.31). The rates of death, new MI, and stroke were 6.5% in the warfarin group and 2.6% in the standard therapy group (RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall rate of rehospitalization for unstable angina was 21% and did not differ significantly between the groups. Four patients in the warfarin group (2.6%) and none in the control group experienced a major bleed (RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46; 95% CI, 1.93 to 15.5; P=0.001). In phase 2, the protocol was modified, and 197 patients were randomized <48 hours from the onset of symptoms to receive warfarin at an adjusted dose that produced a mean INR of 2.3+/-0.6 or standard therapy for 3 months. Eighty-five percent received aspirin in both groups. The rates of CV death, new MI, and refractory angina at 3 months were 5. 1% in the warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI, 0.15 to 1.15; P=0.08). The rates of all death, new MI, and stroke were 5.1% in the warfarin group and 13.1% in the standard therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05). Significantly fewer patients were rehospitalized for unstable angina in the warfarin group than in the control group (7.1% and 17.2%, respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03). Two patients in the warfarin group and 1 in the control group experienced a major bleed, and there was a significant excess of minor bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI, 1.37 to 4.36; P=0.004).. Long-term treatment with moderate-intensity warfarin (INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR, 1.5) plus aspirin appears to reduce the rate of recurrent ischemic events in patients with AIS without ST elevation.

Topics: Administration, Oral; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Aspirin; Coronary Artery Bypass; Electrocardiography; Hemorrhage; Hirudins; Humans; Infusions, Intravenous; Myocardial Infarction; Myocardial Ischemia; Patient Compliance; Pilot Projects; Platelet Aggregation Inhibitors; Warfarin

This study assessed whether combination therapy with aspirin and warfarin for 10 weeks reduces the risk of progression or reocclusion of the unstable coronary artery lesion.. Reocclusion of the culprit coronary artery occurs in up to one third of patients during the 3 months after myocardial infarction (MI) or unstable angina and is associated with increased morbidity and mortality.. Fifty-seven patients presenting with unstable angina or MI who had an identifiable culprit lesion at coronary angiography were randomized in double-blind manner to receive warfarin (target international normalized ratio [INR] 2.0 to 2.5) or placebo in addition to aspirin (150 mg daily). Changes in the culprit lesion were assessed by quantitative angiography in 50 patients after 10 weeks of therapy or after a clinical event. Progression of the culprit lesion was defined as a decrease in minimal lumen diameter > 0.4 mm or a new total occlusion. Regression was defined as an increase in minimal lumen diameter > 0.4 mm.. In subjects randomized to receive warfarin, the culprit lesion was less likely to progress (1 [4%] vs. 8 [33%]) and more likely to regress (5[19%] vs. 2[9%]) than in subjects receiving placebo (p = 0.02). Recurrent MI or a new occlusion at angiography occurred in 2 (7%) of 29 patients receiving warfarin versus 11 (39%) of 28 patients receiving placebo (p = 0.005).. In patients with an acute coronary syndrome, combined therapy with aspirin and warfarin with a target INR of 2.0 to 2.5 for 10 weeks reduces the risk of progression or reocclusion of the culprit coronary lesion.

Topics: Angina, Unstable; Anticoagulants; Aspirin; Coronary Angiography; Coronary Vessels; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Warfarin

The authors examined the bleeding complications in 75 patients who received acenocoumarol and acetylsalicylic acid combined therapy. The studied population suffered from either acute myocardial infarction or unstable angina. Among the 75 patients in two cases (2.7%) appeared serious bleeding and in another 25 cases (33.3%) mild bleeding complications. There were no fatal cases. Comparing these data with literary data, the authors stated that in the study group the proportion of serious complications didn't increase in comparison with patients who received either acenocoumarol, warfarin or acetylsalicylic acid but mild bleeding appeared more frequently. This finding suggests that in high risk patients the combined acenocoumarol-acetylsalicylic acid therapy can be considered under strict control.

Topics: Acenocoumarol; Angina, Unstable; Aspirin; Drug Synergism; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Prothrombin; Warfarin

The aim of this trial was to compare the efficacy of combination antithrombotic therapy with a prostacyclin-sparing aspirin plus anticoagulation versus conventional aspirin plus anticoagulation, when added to antianginal therapy, in patients with unstable angina or non-Q wave myocardial infarction already being treated with aspirin. In a double-blind (for the aspirin) study, 144 prior aspirin users were randomized; 72 patients received controlled-release, prostacyclin-sparing aspirin 75 mg daily plus anticoagulation (intravenous heparin followed by warfarin to maintain the international normalized ratio at 2-3), and 72 patients received conventional aspirin 75 mg daily plus the same anticoagulation. Controlled-release aspirin was formulated to preserve endothelial cell prostacyclin synthesis. Trial therapy was begun by 13.2 +/- 12.3 h of qualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographic changes, myocardial infarction, or death, was analysed by intention to treat. At 12 weeks, events were: [table: see text] Twenty-six of the 42 (62%) recurrent ischaemic events occurred within 7 days of presentation. Four of the 144 patients (3%) experienced a major bleeding complication. It is concluded that in spite of maximal antithrombotic therapy, there is a significant failure rate of medical therapy in aspirin users presenting with unstable angina or non-Q wave myocardial infarction while at rest. Prostacyclin-sparing aspirin offers no clinical benefit over conventional aspirin.

Topics: Adult; Angina, Unstable; Aspirin; Delayed-Action Preparations; Drug Therapy, Combination; Epoprostenol; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Pilot Projects; Rest; Thrombolytic Therapy; Warfarin

The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users.. Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy.. In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina.

Topics: Angina, Unstable; Aspirin; Drug Therapy, Combination; Electrocardiography; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Recurrence; Time Factors; Warfarin

This study was designed to compare the response of unstable angina and non-Q wave myocardial infarction during treatment with antithrombotic therapy.. Antithrombotic therapy is beneficial in patients with these two coronary syndromes.. In a multicenter trial of antithrombotic therapy in unstable angina or non-Q wave myocardial infarction, 358 patients admitted within 48 h of chest pain were randomized to antithrombotic therapy with either 1) aspirin alone, or 2) aspirin plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Admission cardiac enzyme analyses revealed unstable angina in 268 patients and non-Q wave myocardial infarction in 62. Given an event rate of about 25%, this study has a power of 80% to detect a 50% difference between the two groups.. Patients with unstable angina and non-Q wave myocardial infarction were similar with regard to age, gender, coronary risk factors and prior antianginal medication. Primary end points at 12 weeks were recurrent ischemia, infarction and death. [table: see text] In the non-Q wave group, all infarctions and death occurred within the 1st week.. Patients with unstable angina or non-Q wave myocardial infarction on antithrombotic therapy have a similar total number of ischemic events by 12 weeks. However, despite maximal medical therapy with antianginal and antithrombotic medication, patients with non-Q wave infarction have a significantly higher rate of reinfarction and death.

Topics: Adrenergic beta-Antagonists; Aged; Angina, Unstable; Aspirin; Calcium Channel Blockers; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Partial Thromboplastin Time; Prospective Studies; Prothrombin Time; Recurrence; Risk Factors; Thrombolytic Therapy; Time Factors; Treatment Failure; Warfarin

Nine out of 47 (19%) patients on chronic anticoagulation with warfarin, as secondary prophylaxis after myocardial infarction, initially treated with streptokinase, had thromboembolic complications within 4 weeks after sudden (7/25) or gradual (2/22:NS) warfarin withdrawal. The biochemical effects of warfarin withdrawal were repeatedly studied in 20 of the patients during the first 14 days following drug cessation. During the first 4 days, the levels of coagulation factors VII and IX increased more rapidly than proteins C and S. Thus, a gap was created between the factors provoking and inhibiting the coagulation process. Furthermore, plasma concentrations of fibrinopeptide A (FPA) increased, reflecting activation of the coagulation system. These laboratory findings suggest that withdrawal of warfarin creates a transient hypercoagulable state, imposing a risk of thromboembolic events in patients given anticoagulant treatment as secondary prophylaxis following myocardial infarction.

Topics: Adult; Aged; Angina, Unstable; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebrovascular Disorders; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Vascular Diseases; Streptokinase; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Topics: Angina, Unstable; Angioplasty, Balloon; Anticoagulants; Clinical Trials as Topic; Coronary Disease; Heart Ventricles; Heparin; Humans; Myocardial Infarction; Thrombosis; United States; United States Department of Veterans Affairs; Warfarin

Dual antiplatelet therapy with aspirin and clopidogrel has replaced aspirin and systemic anticoagulation with warfarin as the preferred antithrombotic therapy after percutaneous coronary intervention (PCI) with stent placement. However, a number of patients have indications for all 3 drugs. We sought to determine the frequency and type of hemorrhagic complications in patients who undergo systemic anticoagulation with warfarin while receiving aspirin and clopidogrel after a PCI with stent placement.. We performed a retrospective analysis of the Mayo Clinic PCI database and identified 66 consecutive patients who were discharged from hospital after PCI between January 2000 and August 2002 (inclusive) receiving a combination of dual antiplatelet therapy (aspirin and clopidogrel) and systemic anticoagulation (warfarin) to determine the incidence of bleeding and other clinical events during the treatment period.. Six patients (9.2%; 95% CI, 3.5-19.0) reported a bleeding event; 2 patients required a blood transfusion. No patient died or sustained a myocardial infarction or stent thrombosis.. The risk of bleeding may be increased in patients treated with aspirin, a thienopyridine, and warfarin early after PCI with stent placement.

Topics: Aged; Aged, 80 and over; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Coronary Disease; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Stents; Ticlopidine; Warfarin

A 78-year-old woman with unstable angina underwent coronary bypass surgery with complete cardiac revascularization and no immediate postoperative complications. Six days after surgery, during hospitalization for cardiac rehabilitation, the patient developed severe respiratory distress and pulmonary embolism was diagnosed. Color duplex ultrasound revealed the presence of concomitant upper extremity deep vein thrombosis (UEDVT), ipsilateral to the site of placement of a central venous line, in the absence of lower extremity deep vein thrombosis. We describe this case and provide preliminary data from a prospective observational study evaluating the prevalence of catheter-related UEDVT and symptomatic pulmonary embolism (55 and 1.4% respectively) in a series of 71 consecutive coronary bypass surgery patients admitted to a cardiac rehabilitation facility. Catheter-related UEDVT and pulmonary embolism may complicate coronary bypass surgery and should be taken into consideration when managing patients after surgery.

Topics: Aged; Angina, Unstable; Anticoagulants; Coronary Artery Bypass; Echocardiography; Female; Humans; Jugular Veins; Male; Middle Aged; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Ultrasonography, Doppler, Color; Upper Extremity; Venous Thrombosis; Warfarin

Topics: Abdominal Pain; Angina, Unstable; Anticoagulants; Blood Coagulation Disorders; Fever of Unknown Origin; Humans; Male; Medical Errors; Middle Aged; Nausea; Partial Thromboplastin Time; Prothrombin Time; Renal Dialysis; Warfarin

Topics: Administration, Oral; Angina, Unstable; Anticoagulants; Electrocardiography; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Time Factors; Warfarin

To examine the procedural and long term success of coronary stenting in patients presenting with unstable angina and the effect of warfarin on the clinical outcome of these high risk patients.. A nonrandomized, retrospective analysis of patients presenting with unstable angina.. A tertiary care, Canadian university-affiliated teaching hospital.. Of 1250 patients who underwent percutaneous transluminal coronary angioplasty between January 1994 and June 1995, 365 underwent coronary stenting. The study population consisted of the 156 patients presenting with unstable angina who underwent coronary stenting. Patients with Canadian Cardiovascular Society class IV and postinfarction angina were included.. Stent delivery by standard techniques to the target lesion was successful in all patients. At discharge, 88 patients were prescribed warfarin, ticlopidine and acetylsalicylic acid (ASA); the remaining 68 patients received only ticlopidine and ASA. Late clinical outcomes were assessed by telephone interview.. The overall procedural success rate was 96%. One patient died in hospital (0.6%). Other events were abrupt closure (1.9%), myocardial infarction (1.9%) and urgent bypass surgery (1.9%). During follow-up, target vessel reintervention was needed in 19.6% of patients. Early and late clinical outcomes did not differ significantly between anticoagulated patients and those treated with antiplatelet agents alone, but anticoagulated patients had a significantly longer hospital stay.. Coronary stenting in patients with unstable angina was associated with excellent procedural success and favourable late clinical outcomes. Warfarin added no apparent additional clinical benefit to antiplatelet agents in this high risk population.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Aspirin; Coronary Artery Bypass; Coronary Disease; Follow-Up Studies; Humans; Myocardial Infarction; Postoperative Complications; Reoperation; Retrospective Studies; Stents; Ticlopidine; Treatment Outcome; Warfarin

Three clinical cases have been selected to focus on the role of thrombosis in unstable and refractory angina. The histories are abbreviated for simplicity. For example, it can be assumed that non-coronary causes of chest discomfort have been excluded, and that exacerbating factors such as anaemia, hyperthyroidism, hypoxia, arrhythmia, valve disease, obvious coagulopathy, and emotional stress have also been excluded by history, examination, and appropriate testing. These patients all underwent coronary angiography for severe symptoms associated with marked electrocardiographic or haemodynamic changes (and therefore did not undergo radionuclide stress testing) or for symptoms refractory to a medical regimen of rest, reassurance, oxygen, nitrates, cardioselective beta blockers, aspirin 325 mg once or twice daily, heparin 1000 U/h, and sometimes, calcium antagonists and sedatives.

Topics: Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Thrombosis; Female; Heparin; Humans; Male; Middle Aged; Recurrence; Warfarin

A 41-year-old man presenting with unstable angina was found to have diffuse coronary ectasia with a partially occluding thrombus in the proximal left anterior descending artery. Anticoagulation with heparin followed by warfarin resulted in relief of angina and resolution of thrombosis at follow-up angiography 3.5 months later. The patient remains well after three years. Nonatherosclerotic ectatic coronary arteries are prone to thrombosis possibly because of spasm, intimal damage, and blood current eddies. We believe that chronic warfarin therapy may be indicated in many patients with coronary ectasia.

Topics: Adult; Angina, Unstable; Angiography; Coronary Angiography; Coronary Disease; Coronary Thrombosis; Coronary Vessels; Heparin; Humans; Male; Vasodilation; Warfarin

Embolic complications due to prosthetic heart valves are common. The present report documents a left main coronary artery thrombus extending from a Starr Edward's aortic ball valve prosthesis 22 years after its placement. It resulted in unstable angina and a small myocardial infarction. This rare complication illustrates the importance of adequate anticoagulation.

Topics: Adult; Angina Pectoris; Angina, Unstable; Aortic Valve; Coronary Disease; Coronary Thrombosis; Female; Heart Valve Prosthesis; Humans; Myocardial Infarction; Warfarin