warfarin and Coronary-Artery-Disease

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Fibrinolytic Agents; Hemostatics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazoles; Lipids; Organosilicon Compounds; Warfarin

The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) with coronary or peripheral artery disease (CAD or PAD) remain largely unresolved. We, therefore, conducted a meta-analysis to explore the effect of NOACs compared with warfarin in these populations.We systematically searched the Cochrane Library, PubMed, and Embase databases for randomized controlled trials (RCTs) involving NOACs versus warfarin in AF patients with CAD or PAD. A random-effect model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).A total of 7 RCTs were included. In AF patients with CAD, compared with warfarin use, the use of NOACs was associated with reduced risks of stroke/systemic embolism (RR 0.82; 95% CI 0.70-0.96) and intracranial hemorrhage (RR 0.41; 95% CI 0.26-0.63), but NOACs versus warfarin showed similar risks of all-cause death (RR 0.95; 95% CI 0.86-1.05), cardiovascular death (RR 0.95; 95% CI 0.80-1.13), stroke (RR 0.80; 95% CI 0.64-1.00), myocardial infarction (RR 1.00; 95% CI 0.83-1.21), and major bleeding (RR 0.82; 95% CI 0.65-1.04). Among patients with AF and PAD, NOACs versus warfarin had similar risks for stroke (RR 0.93; 95% CI 0.61-1.42), myocardial infarction (RR 1.10; 95% CI 0.64-1.90), all-cause death (RR 0.91; 95% CI 0.70-1.19), major bleeding (RR 1.12; 95% CI 0.70-1.81), and intracranial hemorrhage (RR 0.54; 95% CI 0.16-1.85).NOACs seem to be at least as effective and safe as warfarin in AF patients with CAD. whereas NOACs versus warfarin have similar efficacy and safety in patients with PAD.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Humans; Peripheral Arterial Disease; Warfarin

Patients with atrial fibrillation and concomitant coronary artery disease (CAD) are at higher risk for myocardial infarction or cardiovascular death, often require antiplatelet therapy and are therefore exposed to an increased risk of bleeding. This meta-analysis aimed to compare the efficacy and safety profile of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin in patients with atrial fibrillation and concomitant CAD.. We performed a trial-level meta-analysis of CAD subgroups from four trials of NOAC versus warfarin in patients with atrial fibrillation, comparing the primary trial endpoints (efficacy: stroke or systemic embolic event; safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus those without CAD, and used interaction testing to assess for treatment effect modification.. In total, 58,606 patients with established CAD were included in this meta-analysis. NOACs reduced the risk of stroke/systemic embolic event irrespective of presence of CAD (CAD: 0.76 (0.56-1.04); no CAD: hazard ratio 0.77 (0.56-1.06);. The present meta-analysis of four trials supports that NOACs are safe and at least as effective as warfarin in patients with atrial fibrillation and established CAD.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Pyridines; Randomized Controlled Trials as Topic; Safety; Stroke; Thiazoles; Treatment Outcome; Warfarin

Various antithrombotic agents are clinically used to inhibit the cascade of arterial or venous thrombosis in cardiovascular diseases. Dual antiplatelet therapy with aspirin and P2Y

Topics: Anticoagulants; Area Under Curve; Aspirin; Blood Platelets; Cardiovascular Diseases; Catheter Ablation; Coronary Artery Disease; Fibrinolytic Agents; Hemorrhage; Hemostasis; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Thrombosis; Warfarin

Topics: Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Disease; DNA; Drug Therapy, Combination; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Histones; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis; Warfarin

There is contrasting evidence regarding the optimal antithrombotic regimen after percutaneous coronary stent implantation in patients on oral anticoagulants. A systematic review and meta-analysis was performed to explore the comparative efficacy and safety of dual (an antiplatelet plus an oral anticoagulant) versus triple therapy (dual antiplatelet therapy plus an oral anticoagulant).. We searched the literature for randomized controlled trials (RCTs) or observational studies (OSs) addressing this issue. The efficacy outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction and stent thrombosis. The safety outcomes were major bleeding events and all bleeding events. The analyses were stratified by type of anticoagulant and of antiplatelet used in dual therapy.. Four RCTs and ten OSs met our inclusion criteria including a total of 10,126 patients. 5671 patients received triple therapy whereas 4455 received dual therapy. Median follow up was 12 months. There was no difference between dual therapy and triple therapy regarding efficacy outcomes. Dual therapy significantly reduced the risk of major bleeding (RR 0.66; CI 95% 0.52-0.83; P = 0.0005) and of all bleeding events (RR 0.67, CI 95% 0.55-0.80; P < 0.0001). The effect was consistent regardless of the type of antiplatelet and anticoagulant used in dual therapy.. Dual antithrombotic therapy after coronary stenting in anticoagulated patients significantly reduces bleeding events compared with triple therapy. Dual therapy might be considered in this setting especially when bleeding risk outweighs ischemic risk, although our study was not sufficiently powered to detect a difference in ischemic endpoints.

Topics: Administration, Oral; Anticoagulants; Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Hemorrhage; Humans; Observational Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Warfarin

This review aims to discuss the use of antithrombotic therapy in patients with atrial fibrillation who undergo coronary stenting with emphasis on the use of double vs triple therapy.. When combined with systemic anticoagulation, dual antiplatelet therapy results in an unacceptable increase in bleeding without any improvement in prevention of thrombotic events. Direct oral anticoagulants combined with single antiplatelet therapy have reduced bleeding compared with warfarin plus dual antiplatelet therapy. Triple anticoagulation therapy with warfarin or direct oral anticoagulants leads to an excess of bleeding and is not superior in preventing thrombotic events. Recent randomized, controlled trials have shown a significant reduction in major bleeding events in patients treated with dual antithrombotic therapy compared with triple therapy without any difference in efficacy. These findings call into question whether triple therapy should remain a part of standard practice.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Coronary Artery Disease; Coronary Thrombosis; Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stents; Stroke; Warfarin

Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

Topics: Anticoagulants; Antidotes; Coronary Artery Disease; Drug Discovery; Factor XI; Factor XII; Heart Failure; Heparin; Humans; Peripheral Arterial Disease; Stroke; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

Patients with coronary artery disease who undergo stent implantation and have concomitant indication for long-term oral anticoagulation represent a considerable proportion of the overall population. To date there is still no consensus about the optimal antithrombotic strategy to choose in this kind of patients, due to the difficult balance between an increased risk of bleeding and thromboembolic complications. Therefore, the aim of this study was to perform a meta-analysis to evaluate the risk and benefits of triple antithrombotic therapy versus dual antithrombotic therapy in patients undergoing coronary stent implantation, requiring long-term oral anticoagulation.. We performed formal searches of PubMed, EMBASE, Cochrane central register of controlled trials and major international scientific session abstracts from January 1990 to September 2015 regarding the use of triple antithrombotic therapy (TT) versus dual therapy (DT) in patients undergoing percutaneous coronary stent implantation that required chronic oral anticoagulation. Data regarding study design, inclusion/exclusion criteria, number of patients, and selected endpoints was extracted by 2 investigators. Disagreements were resolved by consensus.. Sixteen trials with a total of 21716 patients undergoing coronary stent implantation with indication to long term oral anticoagulation, were finally included. A total of 6950 received TT, whereas 14766 received DT alone. The follow-up period ranged from 180 to 730 days. Data regarding mortality were available in 21658 patients (99.7 %). All cause mortality was observed in 10.4 % patients in TT versus 16.3 % in DT (OR [95 % CI] =0.73 [0.66-0.80], p <0.001; p. This meta-analysis showed that among patients undergoing coronary stent implantation, requiring chronic OAC, the use of a TT is associated with a significant reduction in overall mortality, recurrent MI and ischemic stroke. As expected, we found a higher incidence of bleedings in patients treated with triple therapy. The benefits in mortality were lost in patients at high-risk for bleedings.

Topics: Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Disease; Drug Therapy; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk; Stents; Ticlopidine; Warfarin

Most patients with mechanical heart valves and many patients with atrial fibrillation will require long-term anticoagulation therapy. For patients with mechanical prosthetic valves, only warfarin is indicated. However, for patients with nonvalvular atrial fibrillation who are at increased risk for embolic stroke, one of the newer antithrombotic medications, such as rivaroxaban, dabigatran, and apixaban, also can be used. Patients with indications for antithrombotic therapy often will have coexisting vascular disease, such as coronary artery disease, requiring concomitant antiplatelet therapy with aspirin alone or more commonly with a dual antiplatelet regimen, aspirin and clopidogrel, or prasugrel or ticagrelor. The risks and benefits of this approach are still not well defined, and current guidelines have included recommendations based primarily on expert opinion.

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Risk Assessment; Ticlopidine; Warfarin

Coronary endarterectomy is an old surgical procedure against coronary artery disease first described by Baily et al. in 1957. Despite its first adverse results, several current publications have shown that coronary endarterectomy with on-pump or off-pump coronary artery bypass grafting can be safely performed with acceptable mortality, morbidity, and angiographic patency rates. Coronary endarterectomy can assure complete revascularization supplying the myocardium with satisfactory blood flow in cases of a diffusely diseased left anterior descending artery or diffuse calcification, thus preventing residual ischemia. Hence, it is important to evaluate current results, rethink this old recipe, and redefine its indications.

Topics: Anticoagulants; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Coronary Vessels; Endarterectomy; Heparin; Humans; Postoperative Care; Safety; Vascular Patency; Warfarin

Atrial fibrillation (AF) and coronary heart disease (CHD) commonly occur together. Previous consensus guidelines were published before the wide availability of novel oral anticoagulants (NOACs) and newer P2Y12 antiplatelet agents. We examine recent evidence to guide management in 3 categories of patients with AF and CHD: patients with stable CHD, nonstented patients with recent acute coronary syndrome, and patients with a coronary stent requiring dual-antiplatelet therapy.. We conducted a literature search by evaluation of PubMed and other data sources including international meeting reports. We critically reviewed recent clinical trial and relevant registry evidence to update European and US consensus documents.. Oral anticoagulation with warfarin or NOACs is required to prevent embolic stroke in AF, and antiplatelet therapy is insufficient for this purpose. Antiplatelet therapy using monotherapy with aspirin is the standard of care in stable CHD. Dual-antiplatelet therapy with aspirin and clopidogrel or a new P2Y12 inhibitor (dual-antiplatelet therapy) is needed to reduce coronary events after an acute coronary syndrome or after percutaneous coronary intervention. Combinations of these agents increase the risk of bleeding, and limited clinical trial evidence suggests that withdrawal of aspirin may reduce bleeding without increasing coronary events.. Available clinical trials and registries provide remarkably little evidence to guide difficult clinical decision making in patients with combined AF and CHD. In patients on triple antithrombotic therapy with vitamin K antagonists, aspirin, and clopidogrel, a single clinical trial indicates that withdrawal of aspirin may reduce bleeding risk without increasing the risk of coronary thrombosis. It is unclear whether this evidence applies to combinations of NOACs and newer P2Y12 inhibitors. Clinical trials of combinations of the newer antithrombotic agents are urgently needed to guide clinical care.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticlopidine; Vitamin K; Warfarin

The pharmacologic management of patients with high-risk coronary artery disease consists of aspirin and a P2Y12 receptor inhibitor. Chronic oral anticoagulation with warfarin is the major treatment strategy to attenuate thromboembolism or stroke in patients with deep vein thrombosis, pulmonary embolism, heart failure and atrial fibrillation. A substantial percentage of the latter group of patients have coronary artery disease and may require stenting with long-term dual antiplatelet therapy in addition to therapy with warfarin to reduce arterial ischemic events in addition to stroke. These new oral anticoagulants have been developed for long-term therapy to overcome the limitations of warfarin. Dabigatran is a direct thrombin inhibitor and its role in patients with acute coronary syndrome is being explored.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Warfarin

Dual antiplatelet therapy is standard treatment following coronary stent implantation. An important minority of patients also require chronic anticoagulation, most commonly for atrial fibrillation. There are no prospective trials to guide the selection of therapy in this situation. In this paper we review the available data and present practice recommendations. It appears that in patients who are not at high risk of bleeding, and in whom both coronary stenting and anticoagulation are considered necessary after careful consideration, drug eluting stents should be avoided as much as possible. Triple therapy with aspirin, clopidogrel and warfarin for one month, followed by the combination of aspirin and warfarin for life is the most reasonable approach.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Drug Therapy, Combination; Evidence-Based Medicine; Hemorrhage; Humans; Patient Selection; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Stents; Treatment Outcome; Warfarin

The current standard in coronary artery stenting is dual antiplatelet therapy with aspirin and clopidogrel, with the duration of therapy primarily based on the use of bare metal or drug-eluting stents. The expanding patient population in whom oral anticoagulation and dual antiplatelet therapy may be indicated poses unique challenges in navigating the delicate balance between the efficacy of these therapies and bleeding risk. Although limited data exist, meaningful recommendations can be made involving individualization of these and other therapies (such as cilostazol) based on the perceived risk of thrombotic stent complications, indication for oral anticoagulant therapy, and bleeding risk.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Stents; Warfarin

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antineoplastic Agents, Phytogenic; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Polymers; Sirolimus; Stents; Thrombosis; 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

Oral anticoagulants have been used in patients with vascular disease for over 40 years, yet their role in the secondary prevention of recurrent cardiovascular (CV) events remains controversial. The objectives of this systematic review are to more reliably determine the role of oral anticoagulants with and without antiplatelet therapy in patients with established coronary artery disease (CAD). Randomized trials in which oral anticoagulants were tested in CAD patients who were treated for at least three months were identified, and each trial was classified by the targeted level of intensity of anticoagulation. Data from the trials were combined using the modified Mantel-Haenszel method, and odds ratios were computed. Data from over 20,000 patients indicated that high-intensity oral anticoagulation (international normalized ratio [INR] >2.8) significantly reduced CV complications and increased bleeding compared with controls. Moderate-intensity oral anticoagulation (INR 2 to 3) also reduced CV complications compared with controls. The combination of moderate-intensity oral anticoagulation and aspirin is more effective and equally as safe as aspirin alone. Low-intensity oral anticoagulation (INR <2) in the presence of aspirin does not reduce CV complications and increases bleeding compared with aspirin alone.

Topics: Anticoagulants; Aspirin; Coronary Artery Disease; Drug Therapy, Combination; Hemorrhage; Humans; International Normalized Ratio; Myocardial Infarction; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Warfarin

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

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

Topics: Adrenal Cortex Hormones; Angioplasty, Balloon, Coronary; Aspirin; Coronary Artery Disease; Coronary Thrombosis; Coronary Vasospasm; Fish Oils; Heparin; Humans; Platelet-Derived Growth Factor; Recurrence; Risk Factors; Warfarin

Topics: Angina Pectoris; Anticoagulants; Coronary Artery Disease; Coronary Disease; Dicumarol; Heparin; Humans; Myocardial Infarction; Phenindione; Toxicology; Warfarin

Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow-up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.

Topics: Aged; Aspirin; Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Disease; Factor Xa Inhibitors; Female; Humans; Long Term Adverse Effects; Male; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Postoperative Complications; Sweden; Thromboembolism; Time-to-Treatment; Warfarin

The aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.. Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events.. A total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y. There was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin.. In RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events.

Topics: Aspirin; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Treatment Outcome; Warfarin

The REDUAL PCI trial (Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) demonstrated that, in patients with atrial fibrillation following percutaneous coronary intervention, bleeding risk was lower with dabigatran plus clopidogrel or ticagrelor (dual therapy) than warfarin plus clopidogrel or ticagrelor and aspirin (triple therapy). Dual therapy was noninferior for risk of thromboembolic events. Whether these results apply equally to patients at higher risk of ischemic events due to lesion complexity or clinical risk factors is unclear.. The primary end point was time to first major or clinically relevant nonmajor bleeding event. The composite efficacy end point was death, thromboembolic event, or unplanned revascularization. Our prespecified subgroup analysis categorized patients by presence of procedural complexity and/or clinical complexity factors at baseline. A modified dual antiplatelet therapy score categorized patients according to degree of clinical risk.. Of 2725 patients, 43.1% had clinical complexity factors alone, 9.9% procedural factors alone, 10.0% both, and 37.0% neither. Risk of the primary bleeding end point was lower in both dabigatran dual therapy groups than warfarin triple therapy groups, regardless of procedural and/or clinical lesion complexity (interaction. In patients with atrial fibrillation undergoing percutaneous coronary intervention, dabigatran 110 and 150 mg dual therapy reduced bleeding risk compared with warfarin triple therapy, with a similar risk of thromboembolic outcomes, irrespective of procedural and/or clinical complexity and modified dual antiplatelet therapy score. Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT02164864.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Risk Assessment; Risk Factors; Stents; Thromboembolism; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

This study assessed baseline cardiovascular (CV) risk factors, concomitant CV medication use, risk of major adverse cardiac events-plus (MACE-plus), and bleeding adverse events (AEs) in patients with idiopathic pulmonary fibrosis (IPF) in three randomized, placebo-controlled phase III trials of pirfenidone.. Patients in the pirfenidone phase III trials were included. Patients with unstable or deteriorating cardiac disease within 6 months before enrollment were ineligible. Medical history at baseline and concomitant CV medication use during treatment were reported. A retrospective, blinded review of AE preferred terms was conducted to identify MACE-plus and bleeding events. Subgroup analyses examined the impact of concomitant CV medication use on how pirfenidone treatment affected clinical outcomes.. In total, 1247 patients were included [n = 623 pirfenidone (2403 mg/day) and n = 624 placebo]. The median age was 68 years, 74% were male, and 65% were current/former smokers. Commonly reported CV risk factors included hypertension (52%), obesity (44%), hypercholesterolemia (23%), and hyperlipidemia (23%). Pre-existing cardiac disorders included coronary artery disease (16%), myocardial infarction (5%), and atrial fibrillation (5%). Lipid-modifying agents (60%), antithrombotic agents (54%), and renin-angiotensin inhibitors (39%) were commonly used concomitant CV medications. The incidences of MACE-plus and bleeding events were similar between the pirfenidone and placebo groups (1.8% and 2.9% for MACE-plus events and 3.7% and 4.3% for bleeding events, respectively). Except for patients receiving heparin, pirfenidone had a beneficial effect compared with placebo on efficacy outcomes regardless of concomitant CV medications.. CV risk factors and comorbidities and use of concomitant CV medications are common in patients with IPF. Pirfenidone did not appear to increase the risk of CV or bleeding events. Use of several concomitant CV medications, including warfarin, did not appear to adversely impact pirfenidone's beneficial effect on efficacy outcomes.. NCT00287716, NCT00287729, and NCT01366209.. F. Hoffmann-La Roche Ltd. and Genentech, Inc.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Atrial Fibrillation; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Disease; Female; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Pyridones; Retrospective Studies; Risk Factors; Treatment Outcome; Warfarin

The study sought to evaluate the effect of dabigatran dual therapy versus warfarin triple therapy across categories of renal function in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy with Dabigatran versus Triple Therapy with Warfarin in Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.. The RE-DUAL PCI (NCT02164864) trial of patients with atrial fibrillation undergoing percutaneous coronary intervention reported that dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) reduced the primary endpoint of major bleeding events (MBE) or clinically relevant nonmajor bleeding events (CRNMBE) compared with warfarin triple therapy, with noninferiority in overall thromboembolic events.. Risk of a first MBE or CRNMBE and the composite of death or thromboembolic event (DTE) or unplanned revascularization were evaluated in 2,725 patients according to baseline creatinine clearance (CrCl) categories: 30 to <50, 50 to <80, and ≥80 ml/min.. Compared with warfarin, dabigatran 110 mg dual therapy reduced risk of MBE or CRNMBE across all categories of CrCl (p for interaction = 0.19). Dabigatran 150 mg dual therapy reduced risk of MBE or CRNMBE regardless of the CrCl category (p for interaction = 0.31). Risk of DTE or unplanned revascularization was similar to warfarin triple therapy for dabigatran 110 mg dual therapy across all CrCl categories. Dabigatran 150 mg dual therapy versus warfarin triple therapy had similar risk for DTE or unplanned revascularization in patients with CrCl 30 to <80 ml/min and lower risk at CrCl ≥80 ml/min (p for interaction = 0.02).. In the RE-DUAL PCI trial, dabigatran dual therapy reduced bleeding events versus warfarin triple therapy irrespective of renal function, with overall similar risks of thromboembolic events but lower risks with dabigatran 150 mg in patients with normal CrCl.

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy.. Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y. Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stents; Time Factors; Treatment Outcome; Vitamin K; Warfarin

The aim of this study was to assess if prior oral anticoagulant agent (OAC) use modifies the lower bleeding risk observed with dabigatran dual therapy (dabigatran twice daily plus a P2Y. In the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial, the primary outcome of major bleeding or clinically relevant nonmajor bleeding was lower with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation who underwent PCI.. A total of 2,725 patients were randomized to dual therapy with dabigatran (110 or 150 mg twice daily) plus clopidogrel or ticagrelor or triple therapy with warfarin plus aspirin and clopidogrel or ticagrelor. Subgroup analysis compared risk for major bleeding or clinically relevant nonmajor bleeding and a composite thromboembolic endpoint in patients with prior OAC use and in those who were OAC treatment naive.. Risk for major bleeding or clinically relevant nonmajor bleeding was reduced with both dabigatran dual therapies compared with warfarin triple therapy in both the prior OAC use group (hazard ratios: 0.58 [95% confidence interval (CI): 0.42 to 0.81] and 0.61 [95% CI: 0.41 to 0.92] with 110 and 150 mg dabigatran, respectively) and the OAC-naive group (hazard ratios: 0.49 [95% CI: 0.38 to 0.63] and 0.76 [95% CI: 0.59 to 0.97] with 110 and 150 mg dabigatran) (p for interaction = 0.42 and 0.37, 110 and 150 mg dabigatran, respectively). The risk for thromboembolic events seemed similar with dabigatran dual therapy (both doses) and warfarin triple therapy across subgroups.. Bleeding risk was reduced with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation after PCI, regardless of whether they were prior OAC users or OAC treatment naive. These results suggest that it is also safe to switch patients on OAC pre-PCI to dabigatran dual therapy post-PCI.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

The aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.. It is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention.. In RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization.. Among patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints.. In this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Diabetes Mellitus; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

The relative efficacy and safety profile of the oral Factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation and established coronary artery disease (CAD) has not been analyzed.. In the ENGAGE AF-TIMI 48 trial, two edoxaban regimens were compared with warfarin in 21,105 patients with atrial fibrillation and CHADS. The reduction in ischemic events with the higher-dose edoxaban regimen versus warfarin was greater in patients with CAD, while bleeding was significantly reduced with edoxaban regardless of CAD status. The efficacy and safety profile of the lower-dose edoxaban regimen relative to warfarin was unaffected by CAD status.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Angiography; Coronary Artery Disease; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Pyridines; Thiazoles; Thrombolytic Therapy; Treatment Outcome; Warfarin

Among atrial fibrillation patients undergoing percutaneous coronary intervention enrolled in PIONEER AF-PCI (An Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention), it is unclear if the observed reduction in bleeding events with rivaroxaban regimens is consistent across a range of the international normalized ratio (INR) among subjects administrated Vitamin K antagonist (VKA)-triple therapy. This analysis compares the occurrence of clinically significant bleeding between rivaroxaban and VKA strategies, according to INR stability of subjects administrated VKA.. A total of 2124 atrial fibrillation patients undergoing percutaneous coronary intervention were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y. Among atrial fibrillation patients undergoing percutaneous coronary intervention, rivaroxaban-based therapy was superior to warfarin plus dual antiplatelet therapy in lowering bleeding outcomes regardless of the INR stability.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01830543.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Coronary Artery Disease; Factor Xa Inhibitors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Vitamin K; Warfarin

After percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment.. In the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35-0.63) for 110 mg and 0.67 (0.50-0.90) for 150 mg]; elective PCI [0.57 (0.43-0.76) for 110 mg and 0.76 (0.56-1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28-0.76) for 110 mg and 0.59 (0.34-1.04) for 150 mg]; or clopidogrel [0.51 (0.41-0.64) for 110 mg and 0.73 (0.58-0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10.. The benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Case-Control Studies; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Elective Surgical Procedures; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Ticagrelor; Warfarin

In the RE-DUAL PCI trial of patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI), dabigatran dual therapy (110 or 150 mg bid, plus clopidogrel or ticagrelor) reduced International Society on Thrombosis and Haemostasis bleeding events compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. This analysis assessed outcomes in relation to patient bleeding and stroke risk profiles, based on the modified HAS-BLED and CHA. The primary endpoint, major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE), was compared across study arms in patients categorized by modified HAS-BLED score 0-2 or ≥3. The composite endpoint of death, thromboembolic event, and unplanned revascularization rates was compared in patients categorized by CHA. Risk of MBE or CRNMBE was lower with dabigatran dual therapy (both doses) versus warfarin triple therapy, irrespective of modified HAS-BLED category (treatment-by-subgroup interaction P-value 0.584 and 0.273 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Risk of the composite thromboembolic endpoint was similar across CHA. Dabigatran dual therapy reduced bleeding events irrespective of bleeding risk category and demonstrated similar efficacy regardless of stroke risk category when compared with warfarin triple therapy.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Equivalence Trials as Topic; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Risk Assessment; Stroke; Thromboembolism; Ticagrelor; Warfarin

We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial.. Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the 18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164 in warfarin group).. PCI occurred infrequently during follow-up. Most patients on study drug at the time of PCI remained on study drug in the peri-PCI period; 19% continued the study drug without interruption. Antiplatelet therapy use post-PCI was variable, although most patients received DAPT. Additional data are needed to guide the use of antithrombotics in patients undergoing PCI.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Drug Monitoring; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Proportional Hazards Models; Pyrazoles; Pyridones; Stroke; Warfarin

This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention.. Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear.. In the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y. Compared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p > 0.05 for all subgroups).. Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543).

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Stents; Stroke; Time Factors; Treatment Outcome; Warfarin

Vitamin K antagonists (VKAs) are known to increase vascular calcification, suggesting increased cardiovascular disease events. Apixaban is an oral direct factor Xa inhibitor superior to warfarin at preventing stroke or systemic embolism and may stabilize coronary atherosclerosis. The potential benefits of avoiding VKA therapy and the favorable effects of factor Xa inhibitors could contribute to cardiovascular disease event reduction. We hypothesized that apixaban inhibits vascular calcification and coronary atherosclerosis progression compared with warfarin in patients with atrial fibrillation (AF). This study is a single-center, prospective, randomized, open-label study. From May 2014 to December 2015, 66 patients with nonvalvular AF who experienced VKA therapy were enrolled. Patients were randomized into either warfarin or apixaban cohorts and followed for 52 weeks. The primary objective is to compare the rate of change in coronary artery calcification (CAC) from baseline to follow-up in apixaban vs warfarin cohorts. The key secondary objective is to compare the rate of incident plaques and quantitative changes in plaque types between patients randomized to either warfarin or apixaban cohorts using serial coronary computed tomography angiography. Expert readers will blindly assess CAC and coronary artery plaques. It is thought that this trial will result in significant differences in CAC and coronary artery plaque progression between the VKA and apixaban. The results are anticipated to provide a novel insight into treatment selection for AF patients. The study is registered at http://www.clinicaltrials.gov (NCT 02090075).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Protocols; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Disease Progression; Electrocardiography; Factor Xa Inhibitors; Female; Humans; Los Angeles; Male; Middle Aged; Plaque, Atherosclerotic; Prospective Studies; Pyrazoles; Pyridones; Research Design; Time Factors; Treatment Outcome; Vascular Calcification; Warfarin; Young Adult

Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE-DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open-label, blinded-endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low-dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ∼ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Protocols; Coronary Artery Disease; Coronary Thrombosis; Dabigatran; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Research Design; Risk Factors; Stents; Stroke; Time Factors; Treatment Outcome; Warfarin

Optimal antithrombotic strategy for patients with concomitant coronary artery disease and atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is still controversial, and the role of novel antithrombotic agents has nerve been tested. Therefore, the aim of this study is to evaluate and overall safety and efficacy profile of the combination of rivaroxaban and ticagrelor in this particular population.. The RT-AF study is an open-label, randomized, active-controlled, multicenter clinical trial with up to 420 subjects enrolled in 5 centers. Eligible patients, who have a history or new onset paroxysmal, persistent, or permanent non-valvular AF, referred to the study centers with indications for PCI will be randomly assigned to receive triple therapy (including warfarin, clopidogrel and aspirin) or dual therapy (rivaroxaban and ticagrelor). All subjects will have clinical follow-up at discharge, at 30 days, 6 months and 12 months. The primary end point is major or clinically relevant non-major bleeding events at 12 months. The major secondary end point is the composite efficacy outcome of death, myocardial infarction, stent thrombosis and ischemic stroke.. The study will be sufficiently powered to provide data primarily regarding the safety of dual therapy with rivaroxaban and ticagrelor over the traditional triple therapy in patients with AF undergoing PCI at 12 months. It will also provide important information regarding the efficacy of the two different antithrombotic regimens. (ClinicalTrials.gov identifier: NCT02334254).

Topics: Adenosine; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Research Design; Rivaroxaban; Ticagrelor; Ticlopidine; Warfarin

A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD.. In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71-1.27, P for interaction=0.12; HR 0.96, 95% CI 0.81-1.13, P for interaction=0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD.. In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Embolism; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Factors; Stroke; Treatment Outcome; Warfarin

The optimal management of patients on oral anticoagulation (OAC) undergoing coronary stenting (PCI-S) is currently undefined. Available evidence suggests that triple therapy of OAC, aspirin and clopidogrel is the most effective, though associated with a relevant incidence of major bleeding. Nearly all data, however, derive from small-size, retrospective studies in which the occurrence of bleeding has seldom been reported according to the ongoing therapy, and the relative contribution to overall bleeding of early haemorrhages has rarely been analysed separately. We design a prospective multicentre registry, which will include patients on OAC undergoing PCI-S.. To prospectively evaluate the post-PCI-S antithrombotic treatment in patients on OAC, relative safety and efficacy of the various regimens, and periprocedural technical and pharmacological management.. Sixty to seventy Italian centres will be enlisted. Patients on OAC at the time of PCI-S will be enrolled and followed up for 12 months. The primary endpoint will be the composite of major/minor bleeding, major adverse cardiac events (e.g., need for urgent re-revascularization, myocardial infarction, death) (MACE), arterial and/or venous thrombosis/thromboembolism. Secondary endpoints will be: major/minor bleeding, MACE, stent thrombosis, arterial or venous thromboembolic complications or both, and the need for blood transfusions. EXPECTED RESULTS AND IMPLICATIONS: This multicentre, prospective registry of patients on OAC undergoing PCI-S will provide for the first time extensive and updated information on current clinical practice, and on the safety and efficacy of the various strategies. As a consequence, clues for the optimal management of this patient subset will be obtained.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Hemorrhage; Humans; Italy; Prospective Studies; Registries; Research Design; Risk Assessment; Stents; Thromboembolism; Thrombosis; Warfarin

This study examines whether obesity accelerates atherogenic progression or adverse outcomes after coronary artery bypass graft (CABG) surgery.. Obesity is a major risk factor for developing coronary heart disease. Whether obesity accelerates disease progression after CABG is unclear.. We examined how body mass index (BMI) related to atherosclerotic graft progression and a clinical composite outcome of death, nonfatal myocardial infarction, stroke, CABG surgery, or angioplasty among 1,314 participants in the Post CABG trial. Participants who had undergone CABG surgery were randomly assigned in a 2 x 2 factorial design to warfarin versus placebo and aggressive low-density lipoprotein cholesterol (LDL-C) lowering with lovastatin 40 to 80 mg/day (to achieve LDL-C of 60 to 85 mg/dl) versus moderate LDL-C lowering with lovastatin 2.5 to 5 mg/day (to achieve LDL-C of 130 to 140 mg/dl). Angiographic progression was assessed by coronary angiography at 4 to 5 years.. Higher BMI was associated with a higher likelihood of angiographic progression (p trend = 0.003) after adjustment for demographic factors, treatment assignment, smoking status, and years since CABG surgery, but not with clinical events (p trend = 0.81). In stratified analyses, higher BMI was associated with angiographic progression in the low-dose lovastatin group (p trend <0.001) but not in the high-dose group (p = 0.03 for test for interaction of BMI and statin treatment). In the high-dose lovastatin group, higher BMI appeared to be protective against clinical events (p trend = 0.06, test of interaction: 0.02).. Higher BMI is strongly associated with atherogenic progression after CABG surgery. Aggressive statin therapy may be protective against obesity-related acceleration of coronary heart disease.

Topics: Anticoagulants; Body Mass Index; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Disease Progression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Obesity; Postoperative Period; Prognosis; Prospective Studies; Warfarin

Although moderate drinking has been associated with lower mortality among patients with coronary heart disease, its safety among patients taking common cardiac medications is unknown.. We studied 1244 men enrolled in the Post-Coronary Artery Bypass Graft (CABG) Trial who had undergone previous coronary bypass surgery. Participants were randomly assigned to lovastatin in low (mean 4 mg) or high (mean 76 mg) doses and to low-dose warfarin (mean international normalized ratio [INR] 1.4, goal INR <2.0) or placebo in a factorial design. Participants underwent routine measurement of alanine aminotransferase (ALT) and INR levels every 6 to 12 weeks for 4 to 5 years. We categorized weekly alcohol intake as abstention (<1 drink), light (1-6 drinks), moderate (7-13 drinks), and heavier (> or =14 drinks).. During follow-up, 66% of men taking warfarin had an INR of 2.0 or higher, and 7% of men had an ALT of 80 IU/L or higher. Maximum INR (P = .72) and ALT (P = .51) levels did not differ across categories of alcohol intake. The risks of an INR of 2.0 or higher were 67%, 66%, 68%, and 61% among non-, light, moderate, and heavier drinkers (P = .86), respectively. The corresponding risks of an ALT of 80 IU/L or more were 8%, 10%, 9%, and 6% (P = .70), respectively.. Moderate drinking did not adversely influence the safety of low-dose warfarin or even high-dose lovastatin among men in this randomized trial, as measured by INR and ALT levels.

Topics: Adult; Aged; Alanine Transaminase; Alcohol Drinking; Anticholesteremic Agents; Anticoagulants; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Humans; International Normalized Ratio; Lovastatin; Male; Middle Aged; Placebos; Warfarin

After coronary endarterectomy, patients have an increased incidence of perioperative myocardial infarction. This study was undertaken to evaluate the possible reduction of perioperative myocardial damage after coronary endarterectomy by intravenous utilization of prostacyclin.. Elective coronary artery bypass grafting was performed in 1,190 patients with diffuse and distal coronary artery disease, in whom endarterectomy of one or more vessels was used as a treatment. All procedures were done with cardiopulmonary bypass. There were 584 patients in the prostacyclin-treated group, and 606 patients in the control group. Prostacyclin (10 ng x kg(-1) x min(-1)) was started 20 minutes before the cross-clamp removal, or at the time of rewarming, and was continued during the first 24 hours after surgery. The incidence of perioperative myocardial damage was detected by creatine kinase-MB enzyme measurement, and electrocardiographic and left ventricular function changes.. A significant decrease in perioperative myocardial damage was detected in the group treated with prostacyclin with respect to the control group.. Prostacyclin infusion initiated during revascularization and continued in the early postoperative course could be successfully employed for the prevention of thrombocyte aggregation and potentially decrease the overall incidence of significant myocardial damage after coronary endarterectomy.

Topics: Anticoagulants; Biomarkers; Coronary Artery Bypass; Coronary Artery Disease; Creatine Kinase; Creatine Kinase, MB Form; Drug Therapy, Combination; Elective Surgical Procedures; Electrocardiography; Endarterectomy; Epoprostenol; Female; Heparin; Humans; Incidence; Infusions, Intravenous; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Treatment Outcome; Ventricular Function, Left; Warfarin

Tissue factor (TF; an initiator of coagulation) and vascular endothelial growth factor (VEGF; a marker of angiogenesis) are involved in the hypercoagulable state associated with malignancy. We investigated their roles in chronic atrial fibrillation (AF), a condition also associated with increased risk of stroke and thromboembolism, as well as a prothrombotic or hypercoagulable state.. We studied 25 patients with AF (20 men; mean+/-SD age, 62+/-13 years) who were compared with 2 control groups in sinus rhythm: 30 healthy control subjects (17 men; mean age, 60+/-9 years) and 35 patient control subjects with coronary artery disease (CAD; 27 men; mean age, 60+/-12 years). Plasma levels of TF, VEGF, and the VEGF receptor sFlt-1 were measured by enzyme-linked immunosorbent assay.. VEGF, sFlt-1, and TF were significantly different between the 3 groups, with abnormal levels in AF and CAD patients compared with control subjects (P<0.001, P=0.022, and P=0.008, respectively). Among the AF patients, TF levels were significantly correlated with VEGF (Spearman's r=0.65, P<0.001) and sFlt (r=0.54, P=0.006) levels. Only TF and VEGF levels were significantly correlated in CAD patients (r=0.39, P=0.02). There were no significant correlations among the healthy control subjects.. Patients with chronic AF have high TF levels, in keeping with the prothrombotic state associated with this arrhythmia. The relationships between TF and VEGF and its receptor sFlt-1 in AF suggest a possible role for VEGF in the hypercoagulable state found in AF, as seen in malignancy and atherosclerosis.

Topics: Anticoagulants; Atrial Fibrillation; Blood Pressure; Case-Control Studies; Chronic Disease; Coronary Artery Disease; Cross-Sectional Studies; Demography; Endothelial Growth Factors; Female; Humans; Lymphokines; Male; Middle Aged; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Thrombophilia; Thromboplastin; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; Warfarin

The purpose of the present study was to study the concept of aspirin resistance or non-responsiveness by investigating the response to long-term aspirin therapy in patients with a former acute myocardial infarction (AMI).. Patients with an AMI (n=202) randomly assigned to aspirin 160 mg/day (n=71), aspirin 75 mg/day and warfarin (INR 2.0-2.5) (n=58) or warfarin (INR 2.8-4.2) (n=73) were evaluated by the PFA-100(R), biochemical variables and clinical events after a mean treatment period of 4 years.. The limit for being an aspirin non-responder was defined as the 95th percentile value in the warfarin alone group (196 s) with the epinephrine cartridge. In patients on aspirin alone 25/71 (35%) were non-responders and on the combination 23/58 (40%). With the adenosine diphosphate (ADP) cartridge only minor differences were found. The levels of thromboxane B(2) in both aspirin groups, in responders as well as in non-responders, were extremely low compared to the warfarin alone group. Evaluating both aspirin groups together (n=129), the levels of soluble P-selectin were significantly higher in non-responders as compared to responders (p=0.012). During the observation period of 4 years with limited number of events, there was a tendency for higher event rates in non-responders as compared to responders (36% vs. 24%, p=0.28).. In our evaluation of the PFA-100(R) a considerable number of post-AMI patients seemed to be non-responders to long-term aspirin therapy in doses of 75 and 160 mg/day. Circulating levels of P-selectin were higher in the non-responders. A tendency to higher incidence of clinical events among non-responders was observed.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Coronary Artery Disease; Drug Resistance; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Function Tests; Warfarin

Obstructive changes often occur in aortocoronary saphenous-vein bypass grafts because of atherosclerosis and thrombosis. We studied whether aggressive lowering of low-density lipoprotein (LDL) cholesterol levels or low-dose anticoagulation would delay the progression of atherosclerosis in grafts.. We studied 1351 patients who had undergone bypass surgery 1 to 11 years before base line and who had an LDL cholesterol level between 130 and 175 mg per deciliter and at least one patent vein graft as seen on angiography. We used a two-by-two factorial design to assign patients to aggressive or moderate treatment to lower LDL cholesterol levels (with lovastatin and, if needed, cholestyramine) and to treatment with warfarin or placebo. Angiography was repeated an average of 4.3 years after base line. The primary angiographic outcome was the mean percentage per patient of grafts with a decrease of 0.6 mm or more in lumen diameter.. As measured annually during the study period, the mean LDL cholesterol level of patients aggressive treatment ranged from 93 to 97 mg per deciliter; with moderate treatment, the range was from 132 to 136 mg per deciliter (P<0.001). The mean international normalized ratio was 1.4 in the warfarin group and 1.1 in the placebo group (P<0.001). The mean percentage of grafts with progression of atherosclerosis was 27 percent for patients whose LDL cholesterol level was lowered with aggressive treatment, and 39 percent for those who received moderate treatment (P<0.001). There was no significant difference in angiographic outcome between the warfarin and placebo groups. The rate of revascularization over four years was 29 percent lower in the group whose LDL cholesterol level was lowered aggressively than in the group receiving moderate treatment (6.5 percent vs. 9.2 percent, P= 0.03).. Aggressive lowering of LDL cholesterol levels to below 100 mg per deciliter reduced the progression of atherosclerosis in grafts. Low-dose warfarin did not reduce the progression of atherosclerosis.

Topics: Adult; Aged; Anticholesteremic Agents; Anticoagulants; Cholesterol, LDL; Cholestyramine Resin; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Coronary Thrombosis; Drug Therapy, Combination; Female; Graft Occlusion, Vascular; Humans; Hypercholesterolemia; Life Tables; Lovastatin; Male; Middle Aged; Saphenous Vein; Treatment Outcome; Warfarin

Coronary embolism is a relatively rare but important non-atherosclerotic cause of acute coronary syndrome, mainly caused by atrial fibrillation and mechanical heart valve thrombosis due to subtherapeutic anticoagulation. There have been increasing reports of bioprosthetic valve thrombosis (BPVT), but thromboembolic events are rare and mainly affect the cerebrovascular system. Coronary embolism is an extremely rare complication of BPVT.. A 64-year-old male presented with non-ST-Elevation myocardial infarction (NSTEMI) to an Australian regional health service. Three years ago, he had undergone Bentall procedure with bioprosthetic aortic valve replacement for severe aortic regurgitation and significant aortic root dilatation. Diagnostic coronary angiography revealed embolic occlusion of first diagonal branch in the absence of underlying atherosclerosis. Prior to NSTEMI presentation, the patient was clinically asymptomatic apart from the progressive increase in transaortic mean pressure gradient on transthoracic echocardiography which was first detected seven months after surgical aortic valve replacement. Transoesophageal echocardiography showed restrictions of the aortic leaflet opening but no evidence of mass or vegetation. After eight weeks of warfarin therapy, the raised aortic valve gradient returned to normal. Lifelong warfarin was prescribed, and patient remained clinically well at 39-month follow-up.. We experienced a case of coronary embolism in a patient with probable BPVT. Reversible bioprosthetic valve hemodynamic deterioration after anticoagulation strongly supports the diagnosis in the absence of histopathology. Early moderate-to-severe hemodynamic valve deterioration warrants further investigations, including cardiac computed tomography and sequential echocardiography, to investigate for probable BPVT and consideration of timely anticoagulation initiation to prevent thromboembolic events.

Topics: Anticoagulants; Aortic Valve; Australia; Bioprosthesis; Coronary Artery Disease; Embolism; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Thromboembolism; Thrombosis; Warfarin

Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting.. The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up.. The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Stents; Vitamin K; Warfarin

The type of periprocedural antithrombotic regimen that is the safest and most effective in percutaneous coronary intervention (PCI) patients on oral anticoagulant (OAC) therapy has not been fully investigated. We aimed to retrospectively investigate the in-hospital bleeding outcomes of patients receiving OAC and antiplatelet therapies during PCI using Japanese nationwide multicenter registry data. A total of 26,938 patients who underwent PCI with OAC and antiplatelet therapies between 2016 and 2017 were included. We investigated in-hospital bleeding requiring blood transfusion, mortality, and stent thrombosis according to the antithrombotic regimens used at the time of PCI: OAC + single antiplatelet therapy (double therapy) and OAC + dual antiplatelet therapy (triple therapy). The antiplatelet agents included aspirin, clopidogrel, and prasugrel. The OAC agents included warfarin and direct OACs. Adjusting the dose of OAC or intermitting OAC before PCI was at each operator's discretion. In the study population [mean age (SD), 73.5 (9.5) years; women, 21.5%], the double therapy and triple therapy groups comprised 5546 (20.6%) and 21,392 (79.4%) patients, respectively. Bleeding requiring transfusion was not significantly different between the groups [adjusted odds ratio (aOR), 0.700; 95% confidence interval (CI), 0.420-1.160; P = 0.165] (triple therapy as a reference). Mortality was not significantly different (aOR, 1.370; 95% CI, 0.790-2.360; P = 0.258). Stent thrombosis was significantly different between the groups (aOR, 3.310; 95% CI, 1.040-10.500; P = 0.042) (triple therapy as a reference). In conclusion, for patients on OAC therapy who underwent PCI, periprocedural triple therapy may be safe with respect to in-hospital bleeding risks. However, further investigations are warranted to establish the safety and efficacy of periprocedural triple therapy.

Topics: Aged; Aspirin; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Japan; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Registries; Retrospective Studies; Warfarin

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Coronary Artery Disease; Dabigatran; Embolism; Female; Health Care Costs; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Peripheral Arterial Disease; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Rivaroxaban; Stroke; United States; Warfarin

The RE-DUAL PCI trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual therapy with dabigatran and a P2Y. The reduction in risk of bleeding without increased risk of thromboembolic events with dual therapy with dabigatran and a P2Y. The primary safety endpoint was the first International Society on Thrombosis and Hemostasis (ISTH) major bleeding event (MBE) or clinically relevant non-major bleeding event (CRNMBE). The efficacy endpoint was the composite of death, thromboembolic event (stroke, myocardial infarction, and systemic embolism) or unplanned revascularization. Cox proportional hazard regression analyses were applied to calculate corresponding hazard ratios and interaction p values for each endpoint.. A total of 655 women and 2070 men were enrolled. The risk of major or CRNM bleeding was lower with both dabigatran 110 mg dual therapy and dabigatran 150 mg dual therapy compared with warfarin triple therapy in female and male patients (for 110 mg: females: HR 0.69, 95% CI 0.47-1.01, males: HR 0.46, 95% CI 0.37-0.59, interaction p value: 0.084 and for 150 mg: females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value: 0.83). There was also no detectable difference in the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization between dabigatran dual therapy and warfarin triple therapy, with no statistically significant interaction between sex and treatment (interaction p values: 0.73 and 0.72, respectively).. Consistent with the overall study results, the risk of bleeding was lower with dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy, and risk of thromboembolic events was comparable with warfarin triple therapy independent of the patient's sex.

Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Warfarin

One of the methods used to treat coronary artery disease (CAD) is anticoagulant therapy, which involves administering anticoagulants to patients that inhibit the arrangement and actuation of clotting factors. Anticoagulant therapy in patients with CAD must be monitored and evaluated because its greatest side effect is the risk of bleeding. The research aimed to analyze anticoagulants used in therapy for CAD patients and identify potential adverse drug reactions and adverse drug interactions.. This was an observational study which collected data retrospectively at Bhayangkara Hospital Surabaya. Patient data had to meet the requirements for inclusion, which were patients treated for a diagnosis of CAD with anticoagulant therapy and were in conditions with or without complications and comorbid diseases. Data were obtained from 40 patient medical records. The data were then processed descriptively.. Most patients were male (80%) and aged 61-70 years old (37.5%). Fondaparinux was administered to 18 patients at a dose of 1 × 2.5 mg SC. Furthermore, enoxaparin was administered to 15 patients at a dose of 2 × 60 mg SC, and seven patients received warfarin at a dose of 1 × 2-4 mg per oral.. The anticoagulants used in this study were fondaparinux 1 × 2.5 mg SC (45%), enoxaparin 2 × 60 mg SC (37.5%), and warfarin 1 × 2-4 mg PO (17.5%). Side effects of the anticoagulants were absent. However, drug interactions with aspirin, clopidogrel, and allopurinol increased the risk of bleeding.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Enoxaparin; Fondaparinux; Humans; Male; Middle Aged; Retrospective Studies; Warfarin

There are scarce data evaluating the effectiveness and safety of rivaroxaban vs. warfarin in non-valvular atrial fibrillation (NVAF) patients with concomitant coronary artery disease (CAD) and/or peripheral artery disease (PAD) treated in routine practice.. Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant (OAC)-naïve NVAF patients receiving rivaroxaban (15-20 mg once daily) or warfarin, with comorbid CAD and/or PAD and ≥12 months of insurance coverage before OAC initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores (standardized differences <0.1 achieved for all covariates after adjustment). Endpoints included a composite of major thrombotic vascular events (MTVEs) (including ischaemic stroke, myocardial infarction, or need for lower limb revascularization/major amputation) and major bleeding. Patients were followed until an event-of-interest, discontinuation/switch of index OAC, insurance disenrolment, or end-of-data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. We identified 3257 rivaroxaban (30.4% received a 15 mg dose) and 5046 warfarin users with NVAF and comorbid CAD and/or PAD. Rivaroxaban was associated with a 32% (95% CI = 8-50%) reduction in the composite of MTVE. No significant difference in major bleeding was observed (HR = 1.13, 95% CI = 0.84-1.52). No statistical interactions were noted in subgroup analyses performed on the MTVE (P-interaction ≥ 0.35 for all) or major bleeding endpoints (P-interaction ≥ 0.09 for all).. Among patients with NVAF and comorbid CAD and/or PAD, rivaroxaban use was associated with a reduced risk of MTVEs vs. warfarin, without significantly increasing major bleeding risk.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Coronary Artery Disease; Databases, Factual; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Thrombosis; Time Factors; Treatment Outcome; United States; Warfarin

The RE-DUAL PCI trial reported that dabigatran dual therapy (110/150 mg twice daily, plus clopidogrel or ticagrelor) reduced bleeding events versus warfarin triple therapy (warfarin plus aspirin and clopidogrel or ticagrelor) in patients with atrial fibrillation who underwent percutaneous coronary intervention, with noninferiority in composite thromboembolic events. In this prespecified analysis, risks of first major or clinically relevant nonmajor bleeding event and composite end point of death, thromboembolic events, or unplanned revascularization were compared between dabigatran dual therapy and warfarin triple therapy in older (≥ 75 years) and younger (< 75 years) patients, using Cox proportional hazard regression. Of 2,725 patients randomized to treatment, 1,026 (37.7%) were categorized into older and 1,699 (62.3%) into younger age groups. Dabigatran 110 mg dual therapy lowered bleeding risk versus warfarin triple therapy in older (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.51 to 0.89) and younger patients (HR 0.40; 95% CI 0.30 to 0.54); interaction p value: 0.0125. Dabigatran 150 mg dual therapy lowered bleeding risk versus warfarin triple therapy in younger patients (HR 0.57; 95% CI 0.44 to 0.74), whereas no benefit could be observed in older patients (HR 1.21; 95% CI 0.83 to 1.77); interaction p value: 0.0013. For the thromboembolic end point, there was a trend for a higher risk with dabigatran 110 mg dual therapy in older patients, compared with warfarin triple therapy, whereas the risk was similar in younger patients. For dabigatran 150 mg dual therapy, the thromboembolic risk versus warfarin triple therapy was similar in older and younger patients. In conclusion, the benefits of dabigatran dual therapy differed in the 2 age groups, which may help dose selection when using dabigatran dual therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Thromboembolism; Ticagrelor; Treatment Outcome; Warfarin

Controversy persists regarding the advisability of anticoagulation for the early period after biological surgical aortic valve replacement (AVR). We aim to examine the impact of various antithrombotic regimens on outcomes in a large cohort of biological AVR patients. Records of 1,111 consecutive adult patients who underwent surgical biological AVR at our institution between 2013 and 2017 were reviewed. Outcomes included stroke, bleeding, and death at 3 and 12 months. Treatment regimens included (1) no therapy, (2) anticoagulants (warfarin or Factor Xa inhibitors), (2) antiplateles (various), and (4) anticoagulants + antiplatelets. Kaplan-Meier analysis was used to track outcomes, and Cox-proportional hazards regression models were conducted to analyze effects of different therapies on adverse events. At 3 months, thromboembolic events were low and not significantly different between the no therapy group (2.2%) and anticoagulation (2.8%) or anticoagulation + antiplatelet (3.6%) or all groups (3.7%). The antiplatelet group was just significantly lower, at 2.2%. However, this was driven by non-stroke cardiovascular events in patients with coronary artery disease. The incidence of death at 3 months was low and not significantly different between all groups. At 12 months, there were no thromboembolic benefits between groups, but bleeding events were significantly higher in the anticoagulation group (no therapy (1.4%), anticoagulation (8.4%), antiplatelet (4.5%), anticoagulation + antiplatelet (7.9%)). In conclusion, none of the antithrombotic regimens showed benefits in stroke or survival at 3 or 12 months after biological AVR. Anticoagulation increased bleeding events. Routine anticoagulation after biological AVR appears to be unnecessary and potentially harmful.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Aspirin; Atrial Fibrillation; Bicuspid Aortic Valve Disease; Bioprosthesis; Coronary Artery Disease; Factor Xa Inhibitors; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Platelet Aggregation Inhibitors; Postoperative Care; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Stroke; Thromboembolism; Warfarin; Young Adult

Postoperative atrial fibrillation (POAF) is common after cardiac surgery and contributes to short- and long-term morbidity, particularly thromboembolism. Anticoagulation for sustained or recurrent POAF is suggested to reduce thromboembolism. Novel oral anticoagulants may present a safe alternative to warfarin with further benefits including shorter hospital length of stay and better patient convenience.. A retrospective analysis was performed on all isolated cases of coronary artery surgery (CABG) at our institution between January 2015 and December 2018, totalling 960 patients. Rates of POAF were examined with particular focus on preoperative factors, postoperative outcomes, and anticoagulation practices.. The incidence of POAF was 31.8% (305 patients) and was higher in older patients (67.6±9.4 yrs vs 63.0±10.7 yrs, p<0.001), those with a history of cerebrovascular disease (14.6% vs 8.7%, p=0.02), those with higher CHADS-VASc scores (2.5±1.3 vs 2.8±1.3, p<0.001) those who had a postoperative return to theatre (2.6% vs 0.8%, p=0.002), and those with new renal failure (4.9% vs 1.8%, p=0.02). Off-pump surgery was associated with lower incidence of POAF (29.8% vs 37.1%, p=0.03). Patients who developed POAF had significantly longer admissions than those without (12.6±10.6 days vs 9.3±16.3 days, p<0.001). In total, 106 patients (11.0%) went home anticoagulated; 77 (72.6%) on warfarin and 29 (27.4% on a NOAC). Readmission for bleeding was higher in patients on anticoagulation (1.0% vs 0.0%, p=0.02), but did not drive readmission for pericardial effusion (0.3% vs 0.6%, p=0.55). No bleeding complications occurred in patients who were discharged on a NOAC. Overall mortality at median of 2 years was 1.8% (17 patients) and no mortality occurred in any patient discharged on anticoagulation.. Postoperative atrial fibrillation is a common adverse event and is linked to higher preoperative and postoperative morbidity. Anticoagulation may be safely started in these patients and use of novel anticoagulation does not appear to increase postoperative complications, although overall numbers are low.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Incidence; Male; Middle Aged; New South Wales; Postoperative Complications; Retrospective Studies; Risk Factors; Thromboembolism; Warfarin

Topics: Anticoagulants; Coronary Artery Bypass; Coronary Artery Disease; Humans; Leg; Male; Middle Aged; Necrosis; Skin; Warfarin

Coronary artery ectasia is characterized by an abnormal dilatation of the coronary arteries. Coronary artery ectasia is observed in 3-8% of patients undergoing coronary angiography and sometimes leads to acute coronary syndrome regardless of the presence or absence of coronary stenosis or atrial fibrillation.. A 61-year-old Indonesian man presented with typical angina that began 1 week before admission and had worsened 3 hours prior to admission. Accompanying symptoms included dyspnea, nausea, and sweating. He was hemodynamically stable and had a history of tobacco smoking and dyslipidemia. An electrocardiogram showed ST-segment depression and T inversion. Laboratory results showed an international normalized ratio of 1.28. Dual antiplatelet therapy was administered along with fondaparinux, and symptoms were alleviated. Coronary angiography showed an ectatic and turbulent mid-distal right coronary artery and slow flow at the first presentation. There was a patent stent in the proximal-mid left anterior descending coronary artery. This patient had previously presented with recurrent acute coronary syndrome and received two coronary stents for the stenotic vessels.. He had right coronary artery ectasia and experienced recurrent acute coronary syndrome. He received dual antiplatelet therapy along with warfarin after stenting of his left anterior descending coronary artery. However, he presented with unstable angina pectoris 7 months before the latest admission and at the latest admission despite a patent stent and no other significant obstructive lesion. The unstable angina pectoris might have been caused by slow flow, microvascular angina caused by small thrombi and/or vasospasm, or epicardial thrombosis at the ectatic coronary artery that dissolved after anticoagulation therapy prior to coronary angiography. Anticoagulant therapy may have a greater benefit than antiplatelet therapy in this patient due to the turbulence and stasis of blood in the ectatic vessel, although coexisting coronary conditions mandated antiplatelet therapy. His international normalized ratio was suboptimal and needed to be improved.. Coronary ectasia may play a role in recurrent acute coronary syndrome, and administration of an anticoagulant to prevent acute coronary syndrome in this patient was in accordance with the varying hemodynamic property of coronary artery ectasia.

Topics: Acute Coronary Syndrome; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Drug Therapy, Combination; Humans; Male; Medication Adherence; Middle Aged; Patient Education as Topic; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

Topics: Algorithms; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Renal Dialysis; Secondary Prevention; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

Treatment patterns and outcomes of individuals with vascular disease who have new-onset atrial fibrillation (AF) are not well characterized.. Among patients with new-onset AF, we analyzed treatment and outcomes in those with or without vascular disease in the ORBIT-AF II registry. Vascular disease was defined as coronary disease with or without myocardial infarction (MI) or revascularization, or peripheral artery disease. The primary outcomes included major adverse cardiovascular or neurological events (MACNE) and major bleeding. Cox proportional hazard models were used to adjust the difference in patient characteristics.. Overall 1920 of 6203 (31.0%) of new-onset AF had vascular disease. In patients with vascular disease, 62.2% of those were treated with direct oral anticoagulants (DOACs) and 23.4% with warfarin. Dual therapy and triple therapy were used in 36.9% and 4.9%, respectively. Vascular disease patients had increased risk of MACNE (adjusted hazard ratio [aHR] 1.83 [95%CIs 1.32-2.55]), but not major bleeding (aHR 1.24 [0.95-1.63]). Among patients with vascular disease, relative to those on warfarin, those treated with DOACs had similar risk for MACNE (aHR 1.20 [0.77-1.87]) but lower risks for bleeding, although it did not reach statistical significance (aHR 0.70 [0.43-1.15]). Concomitant antiplatelet therapy was associated with higher bleeding (aHR 2.27 [1.38-3.73]) with no apparent reduction in MACNE (aHR 1.50 [1.00-2.25]).. Most patients with AF and vascular disease were managed with oral anticoagulation. About half of them were also treated with concomitant antiplatelet therapy, which was associated with increased risk of bleeding, without evidence of improved cardiovascular outcomes.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Registries; Stroke; Treatment Outcome; Warfarin

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Factor Xa Inhibitors; Hemorrhage; Humans; Incidence; Percutaneous Coronary Intervention; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Warfarin

Topics: Biomarkers; Coronary Artery Disease; Coronary Vessels; Humans; Ultrasonography, Interventional; Warfarin

This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin.. Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K-dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown.. In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period.. Patients (mean age 57.9 ± 9.2 years; male 73%; prior and concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin) use, 73% and 97%, respectively) demonstrated overall increases in PAV of 0.41 ± 0.07% (p = 0.001 compared with baseline) and in CaI (median) of 0.04 (interquartile range [IQR]: 0.00 to 0.11; p < 0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial and a range of clinical, ultrasonic, and laboratory parameters, there was no significant difference in the annualized change in PAV in the presence and absence of warfarin treatment (0.33 ± 0.05% vs. 0.25 ± 0.05%; p = 0.17). A significantly greater annualized increase in CaI was observed in warfarin-treated compared with non-warfarin-treated patients (median 0.03; IQR: 0.0 to 0.08 vs. median 0.02; IQR: 0.0 to 0.06; p < 0.001). In a sensitivity analysis evaluating a 1:1 matched cohort (n = 164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated compared with non-warfarin-treated patients. In a multivariate model, warfarin was independently associated with an increasing CaI (odds ratio: 1.16; 95% confidence interval: 1.05 to 1.28; p = 0.003).. Warfarin therapy is associated with progressive coronary atheroma calcification independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Coronary Vessels; Disease Progression; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Ultrasonography, Interventional; Vascular Calcification; Warfarin

Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease.. Non-valvular atrial fibrillation patients aged ≥65 years diagnosed with coronary/peripheral artery disease in the US Medicare population, newly initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected from January 1, 2013 to September 30, 2015. Propensity score matching was used to compare DOACs vs warfarin. Cox proportional hazards models were used to estimate the risk of stroke/systemic embolism, major bleeding, and composite of stroke/myocardial infarction/all-cause mortality.. There were 15,527 apixaban-warfarin, 6,962 dabigatran-warfarin, and 25,903 rivaroxaban-warfarin-matched pairs, with a mean follow-up of 5-6 months. Compared with warfarin, apixaban was associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.37-0.62), major bleeding (HR 0.66; 95% CI, 0.58-0.75), and stroke/myocardial infarction/all-cause mortality (HR 0.63; 95% CI, 0.58-0.69); dabigatran and rivaroxaban were associated with lower rates of stroke/myocardial infarction/all-cause mortality (HR 0.79; 95% CI, 0.70-0.90 and HR 0.87; 95% CI, 0.81-0.92, respectively). Rivaroxaban was associated with a lower rate of stroke/systemic embolism (HR 0.72; 95% CI, 0.60-0.89) and a higher rate of major bleeding (HR 1.14; 95% CI, 1.05-1.23) vs warfarin.. All DOACs were associated with lower stroke/myocardial infarction/all-cause mortality rates compared with warfarin; differences were observed in rates of stroke/systemic embolism and major bleeding. Findings from this observational analysis provide important insights about oral anticoagulation therapy among non-valvular atrial fibrillation patients with coronary/peripheral artery disease and may help physicians in the decision-making process when treating this high-risk group of patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Embolism; Female; Hemorrhage; Humans; Male; Medicare; Myocardial Infarction; Peripheral Arterial Disease; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; United States; Warfarin

Warfarin, a vitamin K antagonist, is associated with systemic vascular calcification. We evaluated whether rivaroxaban (a direct oral factor Xa inhibitor with no interaction with vitamin K) will slow the progression in coronary plaque volumes compared with warfarin in patients with nonvalvular atrial fibrillation using coronary computed tomography angiography.

Topics: Administration, Oral; Anticoagulants; Atherosclerosis; Coronary Angiography; Coronary Artery Disease; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Rivaroxaban; Warfarin

The optimal treatment strategy when combining antiplatelets with oral anticoagulants in patients with atrial fibrillation (AF) and myocardial infarction (MI) or undergoing percutaneous coronary intervention (PCI) is unknown.. The authors investigated the risk of bleeding, ischemic stroke, MI, and all-cause mortality associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in combination with aspirin, clopidogrel, or both in patients with AF following MI and/or PCI.. Danish nationwide registries were used to identify patients with AF who were admitted with a MI and/or underwent PCI, between August 2011 and June 2017, treated with OAC in combination with antiplatelet(s). Patients were followed for 12 months or until an outcome, study end, or death. Standardized absolute risks were estimated on the basis of outcome-specific Cox regression models adjusted for potential confounders. Average treatment effects were obtained as standardized absolute risk differences (ARD) in risks at 3 and 12 months using the g-formula.. Overall, 3,222 patients were included in the study population, of which 875 (27%) were treated with VKA+single antiplatelet therapy (SAPT), 595 (18%) were treated with DOAC+SAPT, 1,074 (33%) were treated with VKA+dual antiplatelet therapy (DAPT), and 678 (22%) were treated with DOAC+DAPT. At 3 months, there was a significant difference in the absolute risk of MI associated with DOAC+SAPT compared with VKA+SAPT (3-month ARD -1.53% (95% confidence interval: -3.08% to -0.11%), with no significant differences found regarding bleeding, ischemic stroke, and all-cause mortality. Compared with VKA+DAPT, DOAC+DAPT was associated with a significantly reduced risk of bleeding (3-month ARD -1.96%, 95% confidence interval: -3.46% to -0.88%), with no significant difference in the absolute risk of all-cause mortality, stroke, or MI.. In a real-world population of AF patients with MI and/or after PCI, the authors found that DOAC in combination with DAPT was associated with a significantly decreased risk of bleeding and similar thromboembolic protection compared with VKA in combination with DAPT.

Topics: Aged; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Clopidogrel; Comorbidity; Coronary Artery Disease; Denmark; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Stroke; Warfarin

To evaluate the outcome of patients with an established indication for oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S) and stratified by the baseline risk of bleeding.. The database of the prospective, multicentre, observational WAR-STENT registry (ClinicalTrials.gov identifier NCT00722319) was analyzed and patients with atrial fibrillation and CHA. At 12-month follow up, MACVE were comparable in the two groups, whereas total, major and minor bleeding, as well as combined MACVE and total bleeding, were significantly more frequent in the non-low bleeding risk group. Upon Cox univariate and multivariable analysis, non-low bleeding risk category confirmed as an independent predictor of major bleeding. The choice of antithrombotic therapy however, appeared not to be influenced by the bleeding risk category at baseline.. In patients with an established indication for OAC undergoing PCI-S, non-low bleeding risk category is the most potent independent predictor of major bleeding. Stratification of the bleeding risk at baseline should therefore be regarded as an indispensable process to be carried out before selection of the antithrombotic therapy.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Clopidogrel; Coronary Artery Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Stents; Thrombolytic Therapy; Ticlopidine; Treatment Outcome; Warfarin; Young Adult

Topics: Anticoagulants; Coronary Artery Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Valve Prosthesis; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; Warfarin

This study sought to investigate the incidence, management, and clinical relevance of atrial fibrillation (AF) during and after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and evaluate outcomes of different antithrombotic strategies.. Uncertainty exists regarding the optimal antithrombotic strategy in patients with AF who are undergoing PCI with DES.. Using a consecutive series of 10,027 patients who underwent DES implantation between 2003 and 2011, we evaluated the overall prevalence and clinical impact of AF. In addition, we compared the efficacy and safety of dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel) and triple therapy (DAPT plus warfarin) among patients with AF. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke.. Overall, 711 (7.1%) patients had a diagnosis of AF at the index PCI. Patients with AF were older, had more comorbid conditions, and more often had a history of strokes; most patients with AF (88.4%) received DAPT rather than triple therapy (10.5%) at discharge. The rate of primary outcome after PCI during the 6-year follow-up period was significantly higher in patients with AF than in those without AF (22.1% vs. 8.0%; p < 0.001). This trend was consistent for major bleeding (4.5% vs. 1.5%; p < 0.001). After multivariable adjustment, the presence of AF was significantly associated with a higher risk of primary outcome (hazard ratio [HR]: 2.33; 95% confidence interval [CI]: 1.95 to 2.79; p < 0.001) and major bleeding (HR: 2.01; 95% CI: 1.32 to 3.06; p = 0.001). Among patients with AF, adjusted risk for the primary outcome was similar between the DAPT group and the triple therapy group (HR: 1.01; 95% CI: 0.60 to 1.69; p = 0.98), but triple therapy was associated with a significantly higher risk of hemorrhagic stroke (HR: 7.73; 95% CI: 2.14 to 27.91; p = 0.002) and major bleeding (HR: 4.48; 95% CI: 1.81 to 11.08; p = 0.001).. Among patients receiving DES implantation, AF was not rare and was associated with increased ischemic and bleeding risk. In patients with AF, triple therapy was not associated with decreased ischemic events but was associated with increased bleeding risk compared to DAPT.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Chi-Square Distribution; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prevalence; Proportional Hazards Models; Republic of Korea; Risk Factors; Stroke; Ticlopidine; Time Factors; Treatment Outcome; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Coronary Artery Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Japan; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Thromboembolism; Warfarin

5% of patients undergoing coronary stenting have an indication for anticoagulation. The aim of our study was to determine the bleeding rates and complications in patients on triple oral antithrombotic therapy (TOAT) after coronary stenting.. We studied patients who underwent coronary stenting in our institution between 2003-2013 and were started on TOAT. Bleeding was the primary outcome.. Totally, 999 patients were treated with TOAT with a median follow up of 127 days. All patients were treated with warfarin as an anticoagulant. 267 patients (26.7%) developed a total of 331 bleeding events. 100 patients had bleeding during the first 30 days of therapy. Major bleeding, minor bleeding, bleeding requiring medical attention, and minimal bleeding developed in 2.9%, 3.3%, 17.2%, and 3.3% of the patients respectively as their most significant bleeding event. Patients with anticoagulation initiated at time of stenting had a significantly higher bleeding rate compared to those already on chronic anticoagulation [adjusted HR (95% CI): 1.37 (1.03-1.79), P = 0.03]. The bleeding likelihood was significantly higher for patients with drug-eluted stents (DES) compared to bare-metal stents (BMS) [adjusted OR (95% CI): 1.52 (1.14 - 2.04), P < 0.05]. Patients with atrial fibrillation had an increased rate of bleeding after 6 month of initiation of TOAT with significantly worse outcomes.. TOAT after coronary stenting is associated with high bleeding rates. Patients with AF had worse outcomes. Patients with newly initiated anticoagulation at time of stenting bleed significantly more than people already on chronic anticoagulation prior to stenting. © 2016 Wiley Periodicals, Inc.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Ohio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stents; Ticlopidine; Time Factors; Treatment Outcome; Warfarin

The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.

Topics: Academic Medical Centers; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies; Warfarin

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.

Topics: Anticoagulants; Antidepressive Agents; Antimetabolites, Antineoplastic; Antitubercular Agents; Arylamine N-Acetyltransferase; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6; Depressive Disorder; Genotype; Isoniazid; Laboratories, Hospital; Methyltransferases; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Pulmonary Embolism; Ticlopidine; Tuberculosis; Vitamin K Epoxide Reductases; Warfarin

The purpose of this study is to assess incidence and risk factors for severe renal dysfunction in patients requiring oral anticoagulation to help guide initial drug choice and provide a rational basis for interval monitoring of renal function for patients prescribed non-vitamin K oral anticoagulants.. Patients on warfarin for atrial fibrillation or venous thromboembolism were consecutively enrolled from January 2007 to December 2010. Baseline kidney function was assessed, and patients were followed to their first decline of kidney function to creatinine clearance<30 mL/min. Multivariate regression assessed independent risk factors for the primary outcome. Severe renal impairment based on baseline kidney function was assessed by Kaplan-Meier analyses.. Of 787 patients identified, 34 were excluded for baseline CrCl <30 mL/min. The mean age was 71 years, and 74% and 31% had hypertension and diabetes mellitus, respectively. At baseline, 23% (n=174) had moderate chronic kidney disease (CKD) (CrCl 30-59mL/min), whereas 31% had mild CKD (CrCl 60-89mL/min). Severe renal impairment occurred in 92 patients (12%), 25% of which was seen within 5.3 months. Of those with baseline stage 3 CKD, 37% developed severe renal impairment. Stage 3 CKD conferred a 14-fold increased risk in the development of severe renal dysfunction (odds ratio 14.5, 95% CI 6.7-31.3, P<.001). Coronary artery disease was also associated with severe renal impairment (odds ratio 2.2, 95% CI 1.3-3.8, P=.004).. Acute and chronic renal dysfunction is common among individuals requiring long-term anticoagulant therapy. Patients with moderate chronic kidney disease and coronary artery disease are at the highest short-term risk of developing severe renal impairment. More frequent monitoring of these patients is warranted.

Topics: Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Creatinine; Female; Humans; Incidence; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Renal Insufficiency, Chronic; Risk Factors; Severity of Illness Index; Stroke; Warfarin

The role of triple antithrombotic therapy vs dual antithrombotic therapy in patients with both atrial fibrillation and coronary artery disease remains unclear. This study explores the differences in treatment practices and outcomes between triple antithrombotic therapy and dual antithrombotic therapy in patients with atrial fibrillation and coronary artery disease.. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (n = 10,135), we analyzed outcomes in patients with coronary artery disease (n = 1827) according to treatment with triple antithrombotic therapy (defined as concurrent therapy with an oral anticoagulant, a thienopyridine, and aspirin) or dual antithrombotic therapy (comprising either an oral anticoagulant and one antiplatelet agent [OAC plus AA] or 2 antiplatelet drugs and no anticoagulant [DAP]).. The use of triple antithrombotic therapy, OAC plus AA, and DAP at baseline was 8.5% (n = 155), 80.4% (n = 1468), and 11.2% (n = 204), respectively. Among patients treated with OAC plus AA, aspirin was the most common antiplatelet agent used (90%), followed by clopidogrel (10%) and prasugrel (0.1%). The use of triple antithrombotic therapy was not affected by patient risk of either stroke or bleeding. Patients treated with triple antithrombotic therapy at baseline were hospitalized for all causes (including cardiovascular) more often than patients on OAC plus AA (adjusted hazard ratio 1.75; 95% confidence interval, 1.35-2.26; P <.0001) or DAP (hazard ratio 1.82; 95% confidence interval, 1.25-2.65; P = .0018). Rates of major bleeding or a combined cardiovascular outcome were not significantly different by treatment group.. Choice of antithrombotic therapy in patients with atrial fibrillation and coronary artery disease was not affected by patient stroke or bleeding risks. Triple antithrombotic therapy-treated patients were more likely to be hospitalized for all causes than those on OAC plus AA or on DAP.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hospitalization; Humans; Male; Markov Chains; Monte Carlo Method; Myocardial Infarction; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pyridines; Registries; Stroke; Ticlopidine; Warfarin

As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk.

Topics: Aspirin; Atrial Fibrillation; Clinical Laboratory Techniques; Coronary Artery Disease; Fibrinolysis; Fibrinolytic Agents; Heart Diseases; Heart Failure; Humans; Thrombelastography; Thrombosis; Tissue Array Analysis; Warfarin

Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention (PCI) compared with dual anti-platelet therapy (DAPT). However, whether warfarin control is associated with reduced cardiovascular events and major bleeding events in patients undergoing PCI with triple antithrombotic therapy is uncertain.. We investigated 1207 consecutive patients who underwent PCI between 2004 and 2011. Major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) defined as all-cause death, acute coronary syndrome, target vessel revascularization, and stroke were compared between groups of patients who received either triple antithrombotic therapy or DAPT.. Triple antithrombotic therapy was administered to 95 (7.9%) patients. The mean international normalized ratio of prothrombin time (PT-INR) was 1.8. The target PT-INR level was set between 1.6 and 2.6 and the ratio (%) of time in the therapeutic range (TTR) was calculated. The median TTR was 78.4% (interquartile range, 67.4-87.6%). Kaplan-Meier survival curves showed that warfarin therapy was not associated with MACCE (p=0.89) and major bleeding (p=0.80). Multivariable Cox regression analysis revealed that triple antithrombotic therapy was not an independent predictor of MACCE and major bleeding.. Triple antithrombotic therapy does not increase the occurrence of MACCE and major bleeding complications, if the warfarin dose is tightly controlled with a lower INR.

Topics: Acute Coronary Syndrome; Aged; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Japan; Male; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prothrombin Time; Retrospective Studies; Stroke; Warfarin

Essentials Vitamin K plays a role in coagulation, and deficiency may promote coronary artery calcification. The role of vitamin K1 in heart disease was assessed using Mendelian randomization in Caucasians. Genetically higher vitamin K1 was associated with a higher risk of ischemic heart disease. Further research elucidating the role of vitamin K1 in ischemic heart disease could be useful.. Background Vitamin K1 is a nutrient in green leafy vegetables; deficiency may promote coronary artery calcification. Warfarin, an anticoagulant used in secondary prevention of thrombotic events, is a vitamin K antagonist. Thrombotic and coronary events may share risk factors. Objectives To clarify the role of vitamin K1 in ischemic heart disease, the risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically determined vitamin K1 levels. Given vitamin K1 is fat soluble, associations with lipids were similarly assessed to assess pleotropic effects via lipids. Methods Separate sample instrumental variable analysis with genetic instruments (Mendelian randomization) was used to obtain an unconfounded estimate of the association of vitamin K1 (based on rs2108622 [CYP4F2], rs4645543 [KCNK9] and rs2192574 [CTNNA2] from a genome-wide association study) with CAD/MI using CARDIoGRAMplusC4D (cases = 64 374; controls = 130 681) and with lipids using Global Lipids Genetics Consortium Results (n = 196 475). Results Vitamin K1 single nucleotide polymorphisms were positively associated with CAD/MI (odds ratio [OR], 1.17 per unit [nmol L(-1) ] of natural log-transformed genetically predicted vitamin K1 ; 95% confidence interval [CI], 1.08-1.26), but not with inverse normal transformed low-density lipoprotein cholesterol (-0.0003; 95% CI, -0.03 to 0.03), high-density lipoprotein cholesterol (0.02; 95% CI, -0.01 to 0.05) or triglycerides (-0.01; 95% CI, -0.04 to 0.02). Considering only rs2108622, which is functionally relevant to vitamin K1 , the association for CAD/MI was stronger (OR, 1.21; 95% CI, 1.08-1.36). Conclusions Vitamin K may cause CAD/MI; whether vitamin K or other determinants of coagulation could be relevant to primary prevention might be worth considering.

Topics: Calcinosis; Case-Control Studies; Cholesterol, LDL; Coronary Artery Disease; Coronary Vessels; Diet; Female; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Male; Mendelian Randomization Analysis; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Polymorphism, Single Nucleotide; Risk Factors; Triglycerides; Vitamin K; Warfarin; White People

The use of antithrombotic medication (ATM) frequently is reported in patients with intracranial hemorrhage (ICH) and is associated with increased mortality. Unfortunately, ATMs sometimes are prescribed and/or used inappropriately. We sought to determine the rate of ATM misprescription/misuse among patients with ICH in a single-center retrospective study.. All patients admitted with ATM-related ICH in 1998-2014 were included. Charts were reviewed and demographic, clinical, and radiologic variables were recorded. The type of ATM, dose, and duration of treatment were analyzed critically. The adequacy of ATM prescription/use was assessed in light of the recommendations and guidelines of the American Heart Association, American Stroke Association, and French National Authority for Health, in effect at the time of admission.. A total of 106 patients with mean age 68 years were identified. Aspirin (53.8%) was the most commonly used drug, followed by oral anticoagulants (31.1%) and clopidogrel (22.6%). In only 80 patients (75.5%), the use of ATM was in line with contemporary guidelines. In the remaining 26 (24.5%), the use of ATMs was inappropriate, including bad drug combination, wrong dose, poor indication, wrong drug class, and/or incorrect treatment duration.. In this Lebanese cohort of patients with ICH, the 24.5% rate of ATM misprescription and/or misuse is highly alarming and the origin of this problem is likely multifactorial. Immediate measures should be undertaken, and efforts should be focused on regaining tight control of ATM prescription and fulfillment, ensuring good patient education, and offering more vigilant oversight on physician licensure.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Clopidogrel; Coronary Artery Disease; Enoxaparin; Female; Fibrinolytic Agents; Humans; Inappropriate Prescribing; Intracranial Hemorrhages; Lebanon; Male; Middle Aged; Platelet Aggregation Inhibitors; Prescription Drug Misuse; Retrospective Studies; Risk Factors; Stroke; Ticlopidine; Warfarin; Young Adult

Topics: Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Chest Pain; Coronary Artery Disease; Drug-Eluting Stents; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Male; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Tachycardia, Ventricular; Treatment Outcome; Warfarin

Many patients with atrial fibrillation (AF) and coronary artery stent deployment are given both antiplatelet drug and warfarin. Little information is available as to the relationship between the antithrombotic therapies in the late phase after stenting and the clinical outcomes of these patients. We examined the clinical outcomes of AF patients 12 months after coronary artery stenting.. We retrospectively examined 146 patients and classified them into three groups according to the antithrombotic therapies [dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT) plus warfarin, and DAPT plus warfarin] 12 months after stenting. We defined the primary endpoint as Thrombolysis in Myocardial Infarction major bleeding and the secondary endpoint as a composite of adverse events (CAE: all-cause death, nonfatal myocardial infarction, intracranial bleeding, and cerebral infarction).. During a median follow-up of 37 months, major bleeding and CAE were observed in 14 (9.6%) and 46 (31.5%) patients, respectively. DAPT plus warfarin was an independent risk factor for major bleeding in a multivariate Cox hazard regression model after adjustment for age, gender, and the type of AF (hazard ratio: 4.20; 95% confidence interval: 1.13-17.27; p=0.033). No significant clinical variables were found for CAE.. Prolonged use of DAPT with warfarin significantly increases the risk of major bleeding in AF patients after coronary artery stenting. Individualized antithrombotic treatment is required in these patients to prevent major bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Stents; Thrombolytic Therapy; Time Factors; Warfarin

Management of antithrombotic agents after implantable cardioverter defibrillator implantation is challenging, particularly among patients with atrial fibrillation and coronary artery disease.. Using data from National Cardiovascular Data Registry(®) Implantable Cardioverter Defibrillator Registry(™) linked with Medicare claims data, we identified 25 180 patients with atrial fibrillation and coronary artery disease who underwent implantable cardioverter defibrillator implantation. Patients were categorized into 5 different groups according to antithrombotic agents prescribed at discharge (any 1 antiplatelet agent [A, n=6538], dual antiplatelet therapy [DA, n=3414], warfarin [n=5264], warfarin+A [n=7994], warfarin+DA [n=1970]). We assessed the primary outcomes occurring within 30 days of hospital discharge. Combinations of DA (adjusted hazard ratio [HR]: 1.39; 95% CI: 1.03 to 1.87), warfarin+A (adjusted HR: 1.32; 95% CI: 1.03 to 1.69), and warfarin+DA (adjusted HR: 2.03; 95% CI: 1.49 to 2.77) were associated with a higher bleeding risk. The risk of major adverse cardiovascular events was higher in patients discharged with A (adjusted HR: 1.69; 95% CI: 1.33 to 2.16), DA (adjusted HR: 2.17; 95% CI: 1.66 to 2.83), and DA+warfarin (adjusted HR: 1.61; 1.16 to 2.24). There was no association between postdischarge antithrombotic agents and thromboembolic events or device-related complications.. Short-term bleeding risk and major adverse cardiovascular events differ with usage patterns of antithrombotic agents, while the risk of thromboembolic events and device-related complications is relatively constant. These data may help clinicians balance risks and benefits when choosing antithrombotic therapy following implantable cardioverter defibrillator implantation.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Coronary Artery Disease; Defibrillators, Implantable; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Male; Medicare; Middle Aged; Patient Discharge; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States; Warfarin

Topics: Anticoagulants; Coronary Artery Disease; Dyspnea; Echocardiography, Transesophageal; Embolism; Foramen Ovale, Patent; Humans; Intracranial Embolism; Magnetic Resonance Angiography; Male; Middle Aged; Multimodal Imaging; Pulmonary Embolism; Renal Artery Obstruction; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

The optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation.. A total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs.. The 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate analysis, TAT was an independent predictor of worse net clinical outcomes (odds ratio 1.63, 95% confidence interval 1.06-2.50) and major bleeding (odds ratio 3.54, 95% confidence interval 1.65-7.58). After propensity score matching, the TAT group still had worse net clinical outcomes and a higher incidence of major bleeding compared with the DAPT group.. In AF patients undergoing DES implantation, prolonged administration of TAT may be harmful due to the substantial increase in the risk for major bleeding without any reduction in MACCE.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chi-Square Distribution; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Pyridines; Republic of Korea; Retrospective Studies; Risk Factors; Stents; Time Factors; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Female; Fibrinolytic Agents; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Stents; Warfarin

Patients treated with warfarin who undergo percutaneous coronary intervention (PCI) present a difficult therapeutic problem. Their baseline demographics, procedural characteristics, and 12-month outcomes are poorly defined. We conducted a retrospective analysis of all patients who underwent PCI at a major UK Cardiac Center from 2012 to 2013. Of the 2,675 patients who underwent PCI, 155 were on long-term warfarin treatment (5.8%). Patients on warfarin were older and more likely to have significant co-morbidity than those not on warfarin. The modified Mehran bleed score was higher in patients treated with warfarin versus those not treated (19.0 ± 5.8 vs 15.4 ± 8.0, p = 0.004). Baseline SYNTAX scores were higher in the patients treated with warfarin (18.5 ± 9.1 vs 12.4 ± 3.8, p = 0.0006) as were residual SYNTAX scores (8.3 ± 1.1 vs 3.8 ± 5.9, p = 0.001). Bare metal stents were more frequently used in warfarin-treated patients than those not treated (44.8% vs 26.3%, p <0.0001). Antiplatelet monotherapy was prescribed after PCI in 14.4% of patients treated with warfarin and 0.7% of non-warfarin (p <0.0001), whereas average dual anti-platelet therapy duration was also significantly shorter (4.3 vs 10.7 months, p <0.0001). At 1-year follow-up, target-vessel revascularization (6.5% vs 3.3%, p <0.05), stent thrombosis (5.0% vs 2.6%, p = 0.14), death (10.1% vs 4.6%, p <0.01), and target-vessel revascularization/stent thrombosis/death (21.6% vs 10.5%, p = 0.004) were all more common in the warfarin cohort. In conclusion, patients treated with warfarin who need PCI are a complex cohort, more likely to receive incomplete revascularization, less intense, and shorter durations of antiplatelet therapy, and have adverse 1-year outcomes. More trials of both current DES and newer DES technologies in warfarin-treated patients are needed.

Topics: Aged; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Dose-Response Relationship, Drug; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Percutaneous Coronary Intervention; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; United Kingdom; Warfarin

Little is known about whether atrial fibrillation is a presentation of coronary disease. There is a paucity of knowledge about their causal relationship and also the impact of different antithrombotic strategies on the subsequent presentation of symptomatic coronary disease.. We studied 7,526 Chinese patients diagnosed with non-valvular atrial fibrillation and no documented history of coronary artery disease. The primary endpoint was the new occurrence of coronary artery disease--either stable coronary artery disease or acute coronary syndrome. After a mean follow-up of 3.2±3.5 years (24,071 patient-years), a primary endpoint occurred in 987 patients (13.1%). The overall annual incidence of coronary artery disease was 4.10%/year. No significant differences in age, sex, and mean CHA2DS2-VASc score were observed between patients with and without the primary endpoint. When stratified according to the antithrombotic strategies applied for stroke prevention, the annual incidence of coronary artery disease was 5.49%/year, 4.45%/year and 2.16%/year respectively in those prescribed no antithrombotic therapy, aspirin, and warfarin. Similar trends were observed in patients with acute coronary syndromes. Diabetes mellitus, smoking history and renal failure requiring dialysis were predictors for primary endpoint in all antithrombotic therapies.. In patients with non-valvular atrial fibrillation, there is a modest association with coronary artery disease. Patients prescribed warfarin had the lowest risk of new onset coronary artery disease.

Topics: Aged; Aspirin; Atrial Fibrillation; Coronary Artery Disease; Female; Fibrinolytic Agents; Hong Kong; Humans; Incidence; Male; Risk Factors; Stroke; Warfarin

Patients with atrial fibrillation and stable coronary artery disease remain a therapeutic challenge because of the different antithrombotic therapies for the 2 conditions and the increase in bleeding with concomitant antiplatelet and anticoagulant medications. Current guidelines extrapolated data from studies of antithrombotic regimens of each condition separately but there is limited evidence for the optimal regimen in patients with atrial fibrillation and stable coronary artery disease beyond the first year after an acute coronary syndrome or stent implantation. In this review we suggest that warfarin monotherapy is sufficient for this patient population beyond 1 year.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Electrocardiography; Follow-Up Studies; Humans; Male; Myocardial Infarction; Stroke; Time Factors; Warfarin

To evaluate the efficacy and safety of evaluation,treatment and follow-up of Kawasaki coronary artery disease based on the clinical severity classification.. This study evaluated 52 patients admitted to the Children's Hospital of Fudan University between July 2005 and December 2013 who were diagnosed with Kawasaki Disease with coronary artery disease.Inclusion criteria were a disease course of more than two months, initial echocardiography showing severity of grade IV and above, and confirmation of disease severity by angiography. Of those studies, 44 were male and eight were female, aged 6 to 142 (average 41) months. Treatment was planned according to protocols in "Suggestions for Management of Kawasaki Coronary Artery Disease" with follow-up. Those patients with grade IV and above confirmed by angiogram were given oral low-dose asprin and warfarin, and those with grade Vb were given coronary artery bypass grafting (CABG) after comprehensive evaluation. Analysis was carried out for diagnosis, treatment, complications, and results of follow-up.. (1) Satisfied images were shown by the angiography of all 52 cases. Forty five patients (86%) had giant aneurysm or multiple aneurysms, with thrombosis found in 10 of 45 patients (22%). Coronary artery lesions occurred in 138 coronary branches, and more common in left anterior descending branch (47 branches, with incidence 34%) and right coronary artery (48 branches, with incidence 35%). There were no complications during or after angiography. (2) After angiography, 49 patients remained at grade IV or above, and three improved to grade III. Ultimately, clinical severities of coronary artery disease included three patients at grade III, 31 patients at grade IV, nine patients at grade Va, and nine patients at grade Vb. (3) Thirty-eight patients were properly using aspirin and warfarin, and two patients with severely elevated international normalized ratio (INR) levels presented with knee joint and gastric hemorrhage, both of which were treated successfully.Patients with INR levels between 1.5 and 2.5 did not show signs of hemorrhage. (4) In follow-up visits between 6 months and 8 years, one patient had representation of thrombosis on angiography, but did not lead to coronary stenosis; four patients were improved from grade IV to either grade III or II. The remaining showed no new thrombotic formation or stenosis. (5) Of the nine grade Vb patients, five underwent coronary artery bypass grafting. The youngest of these patients, a 22 months old girl, died intraoperatively. The remaining four recovered postoperatively and were followed up for 8 to 90 months. One patient had a preoperative left ventricular ejection fraction (LVEF) of only 32.8%, with LVEF remaining abnormal post-CABG, between 35% and 44%. The remaining three patients had normal heart size, cardiac function, and electrocardiogram.Of the other four grade Vb patients, two were contraindicated for surgery due to severe heart failure and loss of myocardial activity. Two other cases are being followed up closely due to their young age of 9 months.. Coronary angiography is safe and efficacious in children, and even in infants.It is the current gold standard tool for grading Kawasaki coronary artery disease. Proper anticoagulation therapy can markedly decrease the incidence of coronary artery occlusion in patients with Kawasaki coronary artery disease. Safe ranges of corrected INR should be between 1.5 and 2.5 after taking warfarin. CABG is an effective treatment for severe coronary artery disease with myocardial ischemia.

Topics: Aspirin; Child; Child, Preschool; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Disease Management; Echocardiography; Electrocardiography; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Treatment Outcome; Ventricular Function, Left; Warfarin

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02-59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan-Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.

Topics: Aged; Anticoagulants; Asian People; Aspirin; Atrial Fibrillation; Blood Coagulation; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; Disease-Free Survival; Drug Monitoring; Drug Therapy, Combination; Female; Hemorrhage; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Republic of Korea; Retrospective Studies; Risk Factors; Stents; Stroke; Ticlopidine; Time Factors; Treatment Outcome; Warfarin

In the era of drug-eluting stents (DES), a long-term dual antiplatelet therapy is required to prevent late stent thrombosis. However, in patients with atrial fibrillation (AF), there is a concern that combining warfarin with dual antiplatelet therapy may increase the risk of bleeding. We analyzed 1274 consecutive patients with coronary artery disease who were treated with coronary intervention from January 2006 through January 2009. Of these, we enrolled 74 AF patients treated with DES and dual antiplatelet therapy as well as warfarin. The primary endpoint was the incidence of major bleeding within 3 years; the predictive factor of major bleeding was also analyzed. To evaluate the efficacy of anticoagulant therapy, time in therapeutic range (TTR) was also measured. The 3-year incidence of major bleeding was 12.2 % (nine of 74 patients). The average observation period was 25.7 ± 20.2 months. Mean TTR value was 44.6 ± 33.0 % and was maintained at a relatively low level. Multivariate analysis revealed that a higher CHADS2 score (2-point more) was an independent predictor of increased risk of major bleeding. Major bleeding in the patients with triple antithrombotic therapy including warfarin occurred at a relatively high rate. Although the higher CHADS2-score indicates a high risk of thrombotic events, it was strongly associated with bleeding complications.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Stroke; Thienopyridines; Ticlopidine; Warfarin

The optimal long-term antithrombotic treatment of patients with coexisting atrial fibrillation and stable coronary artery disease is unresolved, and commonly, a single antiplatelet agent is added to oral anticoagulation. We investigated the effectiveness and safety of adding antiplatelet therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease.. Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence rates were 7.2, 3.8, and 4.0 events per 100 person-years for myocardial infarction/coronary death, thromboembolism, and serious bleeding, respectively. Relative to VKA monotherapy, the risk of myocardial infarction/coronary death was similar for VKA plus aspirin (hazard ratio, 1.12 [95% confidence interval, 0.94-1.34]) and VKA plus clopidogrel (hazard ratio, 1.53 [95% confidence interval, 0.93-2.52]). The risk of thromboembolism was comparable in all regimens that included VKA, whereas the risk of bleeding increased when aspirin (hazard ratio, 1.50 [95% confidence interval, 1.23-1.82]) or clopidogrel (hazard ratio, 1.84 [95% confidence interval, 1.11-3.06]) was added to VKA.. In atrial fibrillation patients with stable coronary artery disease, the addition of antiplatelet therapy to VKA therapy is not associated with a reduction in risk of recurrent coronary events or thromboembolism, whereas risk of bleeding is increased significantly. The common practice of adding antiplatelet therapy to oral VKA anticoagulation in patients with atrial fibrillation and stable coronary artery disease warrants reassessment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Comorbidity; Coronary Artery Disease; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticlopidine; Vitamin K; Warfarin

Coronary artery calcification is a recognised risk factor for ischaemic heart disease and mortality. Evidence is now strong that Mönckeberg's arteriosclerosis, a form of vascular calcification, can be attributable to vitamin K deficiency, but that vitamin K-2, especially the MK-4 form from foods like cheese can be protective. Warfarin blocks the recycling of hepatic and peripheral vitamin K leading to secondary vitamin K deficiency with adverse effects on vasculature, bone, kidneys, brain and other tissues and systems (inflammatory, immune function and neoplasia at least). There is individual susceptibility to vitamin K deficiency and warfarin sensitivity, partly explicable in terms of genetic polymorphisms, epigenetics, diet and pharmacotherapy. The emergence of extensive coronary calcification in a man with atrial fibrillation treated for a decade with warfarin is described by way of illustration and to raise the present clinical management conundrums. Finally, a putative set of recommendations is provided.

Topics: Calcinosis; Coronary Artery Disease; Diet; Factor Xa Inhibitors; Humans; Male; Middle Aged; Monckeberg Medial Calcific Sclerosis; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Warfarin

Topics: Aspirin; Blood Coagulation; Cardiovascular Diseases; Coronary Artery Disease; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Preoperative Period; Stroke; Thrombosis; Warfarin

Uninterrupted oral anticoagulation (OAC) therapy can be the preferred strategy in patients with atrial fibrillation at moderate to high risk of thromboembolism undergoing percutaneous coronary intervention (PCI). To evaluate the need for additional heparins in addition to therapeutic peri-PCI OAC, we assessed bleeding complications and major adverse cardiac and cerebrovascular events in 414 consecutive patients undergoing PCI during therapeutic (international normalized ratio 2 to 3.5) periprocedural OAC. Patients were divided into those with no (n = 196) and with (n = 218) additional use of periprocedural heparins. No differences in major adverse cardiac and cerebrovascular events (4.1% vs 3.2%, p = 0.79) or major bleeding (1.0% vs 3.7%, p = 0.11) were detected, but access site complications (5.1% vs 11.0%, p = 0.032) were less frequent in those without additional heparins. When adjusted for propensity score, patients with additional heparins had a higher risk of access site complications (odds ratio 2.6, 95% confidence interval 1.1 to 6.1, p = 0.022) without any increased risk of any other adverse event. Analysis of 1-to-1 propensity-matched pairs showed a significantly higher risk of access site complication in patients receiving additional AC (13.1% vs 5.7%, p = 0.049). In conclusion, therapeutic warfarin treatment seems to provide sufficient AC for PCI. Additional heparins are not needed and may increase access site complications.

Topics: Administration, Oral; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Humans; Injections, Subcutaneous; Male; Platelet Aggregation Inhibitors; Postoperative Complications; Preoperative Care; Prospective Studies; Thrombosis; Ticlopidine; Time Factors; Treatment Outcome; Warfarin

Vitamin K-antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE(-/-) model of atherosclerosis.. A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE(-/-) mice (10 weeks) received a Western type diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with vitamin K(1) (VK(1), 1.5 mg/g) or vitamin K(1) and warfarin (VK(1)&W; 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.. VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE(-/-) mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.

Topics: Aged; Animals; Apolipoproteins E; Atherosclerosis; Calcinosis; Coronary Artery Disease; Female; Humans; Male; Mice; Mice, Transgenic; Middle Aged; Phenotype; Plaque, Atherosclerotic; Risk; Thromboembolism; Vitamin K; Warfarin

64-multidetector CT angiography (MDCTA) can identify plaques and assess different plaque components (lipid, fibrous tissue and calcifications). The first patient was a 75-year-old-man with atrial fibrillation (AF). Axial 64-MDCTA image of a coronary artery atherosclerotic plaque was obtained, which included the plaque on the outer vessel wall. The authors measured the five points of CT values around the vague center of the plaque with almost equal interval, which was shown in figure 1. Max was 80 Hounsfield unit (HU), and min was 28 HU. After 3 months warfarin therapy (1.5 mg id), max increased to 100 HU, and min increased to 69 HU. The second patient was a 74-year-old-male with hypertension and AF. Max was 61 HU, and min was 37 HU. After 3 months warfarin therapy (2.5 mg id), max increased to 70 HU, and min increased to 50 HU. Warfarin increased CT values of the artherosclerotic plaques in two patients with AF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Humans; Hypertension; Image Processing, Computer-Assisted; Male; Plaque, Atherosclerotic; Tomography, X-Ray Computed; Warfarin

Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important.. From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS(2)) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported.. Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS(2) ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS(2) scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS(2) ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes.. Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Diabetes Complications; Female; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Male; Risk Assessment; Stroke; Ticlopidine; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Ticlopidine; Warfarin

The optimal combination of anticoagulant and antiplatelet therapy following percutaneous coronary intervention with stenting (PCI-S) among patients requiring oral anticoagulation (OAC) is unknown.. We sought to compare the efficacy of a modified dual-antiplatelet regimen (daily aspirin and every other day clopidogrel) to conventional treatment (daily aspirin and daily clopidogrel) following percutaneous coronary intervention (PCI) with drug-eluting stents (DES) among patients who are also discharged on warfarin.. We performed a single-center, retrospective analysis of consecutive patients (n = 454) who underwent PCI-S with DES and were discharged on warfarin and either a conventional (n = 170) or modified (n = 284) antiplatelet regimen between March 2003 and May 2007. In-hospital and 1-year events were compared between the two groups.. There were no differences in 1-year rates of death, myocardial infarction, stent thrombosis or target lesion revascularization between patients receiving a conventional compared to a modified antiplatelet regimen. In-hospital bleeding rates were also similar between the two groups.. An antiplatelet regimen of aspirin with every-other-day clopidogrel may be as efficacious as daily aspirin and clopidogrel among patients receiving warfarin following PCI-S with DES.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Combined Modality Therapy; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Ticlopidine; Treatment Outcome; Warfarin

The optimal antithrombotic strategy for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation is unknown.. The 622 consecutive AF patients undergoing DES implantation were prospectively enrolled. Among them, 142 patients (TT group) continued triple antithrombotic therapy comprising aspirin, clopidogrel and warfarin after discharge; 355 patients (DT group) had dual antiplatelet therapy; 125 patients (WS group) were discharged with warfarin and a single antiplatelet agent. Target INR was set as 1.8-2.5 and was regularly monitored after discharge. The TT group had a significant reduction in stroke and major adverse cardiac and cerebral events (MACCE) (8.8% vs 20.1% vs 14.9%, P=0.010) as compared with either the DT or WS group. In the Cox regression analysis, administration with warfarin (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.31-0.77; P=0.002) and baseline CHADS(2) score >or=2 (HR 2.09; 95%CI 1.27-3.45; P=0.004) were independent predictors of MACCE. Importantly, the incidence of major bleeding was comparable among 3 groups (2.9% vs 1.8% vs 2.5%, P=0.725), although the overall bleeding rate was increased in the TT group. Kaplan-Meier analysis indicated that the TT group was associated with the best net clinical outcome.. The cardiovascular benefits of triple antithrombotic therapy were confirmed by reducing the MACCE rate, and its major bleeding risk might be acceptable if the INR is closely monitored.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Prospective Studies; Risk Factors; Stroke; Thromboembolism; Ticlopidine; Treatment Outcome; Warfarin

Previous data on bleeding after percutaneous coronary intervention (PCI) have been obtained primarily from randomized trials that focused on in-hospital bleeding. The incidence of late bleeding after PCI, its independent predictors, and its prognostic importance in clinical practice has not been fully addressed.. We evaluated 22 798 patients aged >65 years who underwent PCI from December 1, 2003, to March 31, 2007, in Ontario, Canada. Cox proportional hazard models were used to determine factors associated with late bleeding, which was defined as hospitalization for bleeding after discharge from the index PCI, and to estimate risk of death or myocardial infarction associated with late bleeding. We found that 2.5% of patients were hospitalized for bleeding in the year after PCI, with 56% of bleeding episodes due to gastrointestinal bleed. The most significant predictor of late bleeding was warfarin use after PCI (hazard ratio [HR], 3.12). Other significant predictors included age (HR, 1.41 per 10 years), male sex (HR, 1.24), cancer (HR, 1.80), previous bleeding (HR, 2.42), chronic kidney disease (HR, 1.93), and nonsteroidal antiinflammatory drug use (HR, 1.73). After adjusting for baseline covariates, hospitalization for a bleeding episode was associated with a significantly increased 1-year hazard of death or myocardial infarction (HR, 2.39; 95% CI, 1.93 to 2.97) and death (HR, 3.38; 95% CI, 2.60 to 4.40).. Hospitalization for late bleeding after PCI is associated with substantially increased risk of death and myocardial infarction. The use of triple therapy (i.e., aspirin, thienopyridine, and warfarin) is associated with the highest risk of late bleeding.

Topics: Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Female; Hospitalization; Humans; Incidence; Male; Myocardial Infarction; Postoperative Hemorrhage; Prognosis; Risk Factors; Survival Analysis; Warfarin

We sought to investigate the association between new-onset atrial fibrillation after coronary artery bypass graft (CABG) (post-operative atrial fibrillation [POAF]) and long-term mortality in patients with no history of atrial fibrillation.. POAF predicts longer hospital stay and greater post-operative mortality.. A total of 16,169 consecutive patients with no history of AF who underwent isolated CABG at our institution between January 1, 1996, and December 31, 2007, were included in the study. All-cause mortality data were obtained from Social Security Administration death records. A multivariable Cox proportional hazards regression model was constructed to determine the independent impact of new-onset POAF on long-term survival after adjusting for several covariates. The covariates included age, sex, race, pre-operative risk factors (ejection fraction, New York Heart Association functional class, history of myocardial infarction, index myocardial infarction, stroke, chronic obstructive pulmonary disease, peripheral arterial disease, smoking, diabetes, renal failure, hypertension, dyslipidemia, creatinine level, dialysis, redo surgery, elective versus emergent CABG, any valvular disorder) and post-operative adverse events (stroke, myocardial infarction, acute respiratory distress syndrome, and renal failure), and discharge cardiac medications known to affect survival in patients with coronary disease.. New-onset AF occurred in 2,985 (18.5%) patients undergoing CABG. POAF independently predicted long-term mortality (hazard ratio: 1.21; 95% confidence interval: 1.12 to 1.32) during a mean follow-up of 6 years (range 0 to 12.5 years). This association remained true after excluding from the analysis those patients who died in-hospital after surgery (hazard ratio: 1.21; 95% confidence interval: 1.11 to 1.32). Patients with POAF discharged on warfarin experienced reduced mortality during follow-up.. In this large cohort of patients, POAF predicted long-term mortality. Warfarin anticoagulation may improve survival in POAF.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Disease; Female; Georgia; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Postoperative Complications; Proportional Hazards Models; Registries; Retrospective Studies; Risk Factors; Warfarin

Topics: Aortic Valve Stenosis; Coronary Artery Bypass; Coronary Artery Disease; Enoxaparin; Fibrinolytic Agents; Heart Valve Prosthesis Implantation; Hematoma; Humans; International Normalized Ratio; Male; Middle Aged; Postoperative Complications; Rupture; Sigmoid Diseases; Warfarin

Topics: Anticoagulants; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Gene Expression Profiling; Genetic Testing; Humans; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

A 62-year-old woman presented to the emergency department with sudden collapse, intractable ventricular fibrillation, and an inferior wall myocardial infarction (MI). An emergent cardiac catheterization showed a totally occluded right coronary artery (RCA). A bare-metal stent was placed in the stenosis, resulting in thrombolysis in myocardial infarction (TIMI)-III flow with 0% residual stenosis. Four days after stenting, the patient developed chest pain. A repeat cardiac catheterization showed a totally occluded stent. The patient was subsequently tested using a thrombelastograph (TEG) Platelet Mapping assay to exclude clopidogrel resistance. The assay confirmed the patient to be non-responsive to clopidogrel for the inhibition of platelet ADP receptors. In an attempt to increase ADP inhibition, the ADP antagonist was changed to ticlopidine. Further testing was confounded by the presence of abciximab; however, the patient has remained free of cardiac events.

Topics: Abciximab; Antibodies, Monoclonal; Anticoagulants; Blood Platelets; Cardiac Catheterization; Clopidogrel; Coronary Artery Disease; Drug Resistance; Female; Fibrinolytic Agents; Humans; Immunoglobulin Fab Fragments; Middle Aged; Platelet Activation; Platelet Aggregation Inhibitors; Stents; Thrombelastography; Ticlopidine; Warfarin

A 24-year-old male patient with anterior myocardial infarction, caused by embolization from mitral valve prosthesis due to inadequate anticoagulation is presented. The patient underwent cardiac catheterization within 90 minutes of arrival. Angiography showed total occlusion of the left anterior descending coronary artery (LAD) after the second diagonal branch. Thrombus was extracted with export catheter from LAD, and coronary artery perfusion was restored. The pain disappeared completely immediately after this intervention. Transoesophageal echocardiography performed 2 days later revealed no thrombus at the prosthetic valve. In conclusion, this case demonstrated that coronary embolism may occur even without prosthetic valve thrombus or dysfunction with suboptimal International Normalized Ratio levels, and can be successfully treated with coronary angiography with clot extraction with aspiration catheter (Export XT 6F Medtronic) only, without stenting.

Topics: Adrenergic beta-Antagonists; Adult; Angioplasty, Balloon; Anticoagulants; Antihypertensive Agents; Aspirin; Coronary Angiography; Coronary Artery Disease; Echocardiography, Transesophageal; Embolism; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Myocardial Infarction; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin

Warfarin has been shown to accelerate vascular calcification in experimental animals, and possibly humans, through inhibition of the vitamin K-dependent protein matrix gla protein, a potent inhibitor of tissue calcification. We performed a cross-sectional analysis of the extent of coronary artery calcification (CAC) in patients without coronary heart disease, currently taking or referred for warfarin therapy. The primary end point was severity of CAC measured by electron beam computed tomography attributed to duration of warfarin use, after adjustment for cardiovascular risk factors. Seventy patients (46 men, mean age 68 +/- 13 years) were enrolled from three groups of warfarin use duration: (1) <6 months (n = 31, mean duration 1 +/- 1 months), (2) 6-24 months (n = 11), and (3) >24 months (n = 28, mean 67 +/- 40 months). Overall, the mean total CAC score (Agatston) was 293 +/- 560: group 1 (175 +/- 285), group 2 (289 +/- 382), and group 3 (426 +/- 789). In univariate analysis, there was a nonsignificant trend to increased CAC with increasing warfarin exposure (P = 0.18). Bivariate analysis revealed no correlation between warfarin duration and CAC score (r = 0.075, P = 0.537). Linear regression for the independent variable coronary calcium score controlling for warfarin treatment duration and intensity (duration of warfarin use months x mean INR), Framingham risk score, and creatinine clearance showed that only the Framingham risk score was associated with CAC (P = 0.001). Among patients without known coronary heart disease, duration of warfarin exposure was not associated with extent of coronary calcification.

Topics: Aged; Aged, 80 and over; Anticoagulants; Calcinosis; Cardiomyopathies; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Linear Models; Male; Middle Aged; Risk Factors; Warfarin

Topics: Anticoagulants; Aorta, Thoracic; Arm; Clopidogrel; Coronary Artery Disease; Echocardiography, Transesophageal; Humans; Ischemia; Male; Middle Aged; Platelet Aggregation Inhibitors; Thromboembolism; Ticlopidine; Warfarin

Long-term warfarin therapy is assumed to increase bleeding and access site complications after coronary angiography and it is often recommended to postpone invasive procedures to reach international normalized ratio (INR) levels <1.8. To assess the safety and feasibility of diagnostic coronary angiography during uninterrupted warfarin therapy, we retrospectively analyzed all consecutive patients (n = 258) on warfarin therapy referred for diagnostic coronary angiography in 2 centers with long experience in uninterrupted warfarin therapy during coronary angiography and in 1 center with a policy of preprocedural warfarin pause. An age- and gender-matched control group (n = 258) with similar disease presentation (unstable or stable symptoms) was collected from each center. Radial access was used in 56% of patients in the warfarin group and in 60% of controls (p = 0.21). There was no difference in access site and bleeding complications (1.9% vs 1.6%) or major adverse cardiovascular and cerebrovascular events (0.4% vs 0.8%) between the warfarin group and their controls. Warfarin was interrupted in 80 patients (31%), and bridging therapy was used in 24 of these patients (30%). INR levels were higher in the uninterrupted warfarin group (2.3 vs 1.9, p <0.001), but the incidence of access site complications was not higher (1.7%) than in patients (n = 80) with a warfarin pause (2.5%) or in patients with pause and bridging therapy (8.3%). Need for blood transfusions (n = 2) occurred only in patients with bridging therapy. Access site complications were more common in the 22 patients with supratherapeutic anticoagulation (INR >3) than in patients with therapeutic periprocedural INR (9.1% vs 1.5%, p <0.05). In conclusion, a simple strategy of performing coronary angiography during uninterrupted therapeutic warfarin anticoagulation is a tempting alternative to bridging therapy and is likely to lead to considerable cost savings.

Topics: Aged; Anticoagulants; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Feasibility Studies; Female; Humans; International Normalized Ratio; Male; Retrospective Studies; Risk Factors; Time Factors; Warfarin

The use of antiplatelet therapy in combination with oral anticoagulants remains controversial. The objective of this study was to estimate and compare the incidence of adverse and coronary event rates between patients receiving warfarin monotherapy or warfarin and antiplatelet combination therapy.. This was a retrospective, longitudinal, pharmacoepidemiologic analysis. Adult patients receiving warfarin managed by an anticoagulation service who had documented the use of antiplatelet agents (eg, aspirin, clopidogrel, and/or dipyridamole) [ie, the combination-therapy cohort] or their nonuse (ie, the monotherapy cohort) were identified as of September 30, 2005. Utilizing integrated, electronic medical records, anticoagulation-related adverse events (eg, death, hemorrhage, or thrombosis) and coronary events were identified during a 6-month follow-up period (October 2005 through March 2006). The proportions of events were compared between cohorts. Independent associations between the cohorts and the outcomes were assessed with adjustment for potential confounding factors.. Data from 2,560 patients in the monotherapy cohort and 1,623 patients in the combination-therapy cohort were analyzed. Patients in the combination-therapy cohort were more likely to have had anticoagulation-related hemorrhages (4.2% vs 2.0%, respectively; unadjusted p < 0.001) and coronary events (0.9% vs 0.3%, respectively; p = 0.009), but not death (0.1% vs 0.2%, respectively; unadjusted p = 0.186) or thrombotic events (0.3% vs 0.4%, respectively; unadjusted p = 0.812). With adjustment, combined warfarin and antiplatelet use was independently associated with hemorrhagic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.44 to 5.28), but not with coronary events (OR, 0.99; 95% CI, 0.37 to 2.62).. At the population level, the hemorrhagic risk associated with warfarin therapy combined with antiplatelet therapy appears to outweigh the benefits. These findings suggest that clinicians should carefully consider the risks and benefits when recommending combined antiplatelet therapy for patients receiving warfarin who do not meet the evidence-based criteria for such therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Coronary Artery Disease; Dipyridamole; Drug Therapy, Combination; Female; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Thromboembolism; Ticlopidine; Treatment Outcome; Warfarin

Topics: Anticoagulants; Coronary Aneurysm; Coronary Artery Disease; Diagnosis, Differential; Electrocardiography; Female; Humans; Male; Stents; Tomography, Emission-Computed; Tomography, X-Ray Computed; Warfarin

The objective of this study was to highlight the need for investigation of antiphospholipid (aPL) antibodies in patients presenting with myocardial infarction (MI) and normal coronary arteries at angiography. We present five patients who were found to have had an MI without evidence of atherosclerosis. All had aPL antibodies and thus fulfilled the diagnosis of antiphospholipid syndrome (APS). Who did not have recurrent events on long-term anticoagulation maintaining an international normalised ratio of 3-4. This study suggests that APS is probably a major cause of MI in those with normal coronary arteries at angiography. It is an important diagnosis to make as they do not require anti-atherosclerotic treatment but appear, from this case series, to do well on high-dose warfarin. Further clinical studies are necessary to look at prevalence and best management in these patients.

Topics: Adult; Age of Onset; Anticoagulants; Antiphospholipid Syndrome; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Myocardial Infarction; Treatment Outcome; Warfarin

Diabetes mellitus patients after aorto-coronary bypass operation constitute a patient cohort at largely increased risk for secondary coronary events. Antiplatelet agents and antithrombotic agents are applied for secondary prevention. Up to now, secondary prevention has not been addressed specifically in the cohort of diabetic patients after bypass operation. Hence therapeutic recommendations are derived from the global cohort of CAD patients and based on risk assessment rather than on specific data. Since diabetic patients after myocardial infarction are at particularly high risk, combined therapy with clopidogrel and ASS may be considered even with restricted resources in the health system. Oral anticoagulation with coumadin constitutes an effective alternative to dual anti-platelet therapy. Under specific conditions (ventricular aneurysms, EF < 30%, or certain conditions in coronary anatomy) oral anticoagulants should be considered more liberally than currently.

Topics: Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Thrombosis; Ticlopidine; Warfarin

Vitamin K antagonists, known as oral anticoagulants, affect the synthesis and function of the matrix Gla protein, which is a potent inhibitor of tissue calcification. We performed multislice spiral computed tomography in 86 patients (53 men, mean age 71 +/- 8 years) with calcific aortic valve disease to quantitate the amount of calcification in the aortic valve and coronary arteries. Patients with long-term oral anticoagulation therapy (mean duration 88 +/- 113 months; n = 23) were compared with those without anticoagulation (n = 63). No differences were found in the demographic, clinical, or echocardiographic characteristics between the 2 study groups. Patients on oral anticoagulant therapy had increased coronary calcium (coronary Agatston score 1,561 +/- 1,141 vs 738 +/- 978, respectively; p = 0.024) and valvular calcium (valvular Agatston score 2,410 +/- 1,759 vs 1,070 +/- 1,085, respectively; p = 0.002) compared with patients without anticoagulation treatment. The results of our study have demonstrated that oral anticoagulation may be associated with increased valvular and coronary calcium in patients with aortic valve disease, presumably due to decreased activation of the matrix Gla protein.

Topics: Administration, Oral; Aged; Anticoagulants; Aortic Valve; Calcinosis; Coronary Artery Disease; Female; Heart Valve Diseases; Humans; Male; Tomography, Spiral Computed; Treatment Outcome; Warfarin

To evaluate recent trends, we examined longitudinal national data on the outpatient use of warfarin in atrial fibrillation (AF), beta-blockers and aspirin in coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors (ACEIs) in congestive heart failure (CHF).. Previous studies indicate that specific cardiac medications are underutilized.. We used the National Disease and Therapeutic Index (NDTI) (produced by IMS HEALTH, Plymouth Meeting, Pennsylvania) for 1990 to 2002, and the National Ambulatory Medical Care Surveys (NAMCS) for 1990 to 2000 to follow nationally representative samples of outpatient visits. For visits by patients with AF (total n = 14,634 visits), CAD (n = 35,295), and CHF (n = 33,008), we examined trends in the proportion of visits with the selected medications reported.. Warfarin use in AF increased from 12% in 1990, to 41% in 1995, to 58% in 2001 in NDTI; a similar moderation of recent increase was seen in NAMCS. For CAD in NDTI, beta-blocker use increased slowly from 19% in 1990, to 20% in 1995, then to 40% in 2001; NAMCS showed this same pattern. Aspirin use in CAD in NDTI increased from 18% in 1990, to 19% in 1995, to 38% in 2001; NAMCS, however, showed lower use rates. For NDTI, ACEI use in CHF increased from 24% in 1990 to 36% in 1996, but increased to only 39% by 2001, a general pattern also seen in NAMCS.. Both national datasets demonstrate continuing underutilization of these cardiac medications of proven benefit. Although use is increasing, it remains lower than expected, and some increases noted in earlier years have slowed. Substantial public health benefits would result from further adoption of these effective therapies.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Atrial Fibrillation; Cardiovascular Agents; Coronary Artery Disease; Drug Therapy; Drug Utilization; Health Care Surveys; Heart Failure; Hematologic Agents; Humans; Longitudinal Studies; Office Visits; United States; Warfarin

Topics: Anticoagulants; Aspirin; Coronary Artery Disease; Dalteparin; Heparin, Low-Molecular-Weight; Humans; Randomized Controlled Trials as Topic; 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

Our objective was to document change in stent usage in a single practice over time and to study "off-label" compared to Food and Drug Administration (FDA)-approved indications. Although only two intracoronary stents have been approved by the FDA, the relatively limited approved indications do not account for the dramatic increase in stent implantation. This increase has important implications for patient health care delivery. This study of stent usage in a single center over a 36-mo period included all patients treated with coronary stents at the Mayo Clinic from January 1993-December 1995, and evaluated the relative difference in frequency between "off-label" and FDA-approved indications for implantation. During the 36-mo period of study, 3,614 interventional procedures were done and one or more stents were placed in 25.4% of patients. The proportion of patients receiving stents increased throughout this time: during the first 6-mo period, stents were placed in 6.2% of procedures; during the last 6-mo period, stents were placed in 46.3% of procedures, an eightfold increase. During the final 6 mo, an unapproved device or an unapproved indication for an approved device constituted 59.4% of all stent procedures. In addition, use of the non-FDA-approved adjunctive treatment regimen without warfarin increased from 2.9% in the first 6-mo period of observation to 82.7% in the last 6 mo. The use of stents increased strikingly over a 36-mo period, from 6% to 46% of all procedures. The majority of implantations were performed either for an "off-label" unapproved indication or with an unapproved device.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Chemotherapy, Adjuvant; Coronary Artery Disease; Coronary Disease; Female; Humans; Male; Practice Patterns, Physicians'; Risk Factors; Saphenous Vein; Stents; United States; United States Food and Drug Administration; Warfarin

Interest in coronary stenting has exploded since the publication of several large, randomized trials, and (due to the rapidity of patient recruitment into non-randomized trials) volumes of data are quickly abandoning "old standards" of patient selection, operative technique, and postoperative anticoagulation management. In this editorial, suggestions are offered to help clinicians take the leap from outdated Food and Drug Administration-guided regulations to off-label use and withholding of anticoagulation.

Topics: Anticoagulants; Coronary Artery Disease; Humans; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Stents; Warfarin