warfarin and Acute-Coronary-Syndrome

The combination of oral anticoagulants with platelet inhibitors has been widely investigated in patients with coronary stenting and concomitant atrial fibrillation. In these patients, default therapy after percutaneous coronary intervention in acute coronary syndrome is clopidogrel plus non-vitamin K antagonist oral anticoagulant, omitting aspirin. However, in view of the high thromboembolic risk associated with acute coronary syndrome and the number of poor metabolizers for clopidogrel, investigation of alternative P2Y12-inhibitors is mandatory. This prospective, multicenter, open-label, registry-based, randomized, controlled trial aims to show the non-inferiority of dabigatran plus ticagrelor versus dabigatran plus clopidogrel in patients on chronic anticoagulants who undergo percutaneous coronary intervention in acute coronary syndrome. The primary end point is major bleeding as defined by the Bleeding Academic Research Consortium bleeding definition.

Topics: Acute Coronary Syndrome; Anticoagulants; Clopidogrel; Dabigatran; Drug Therapy, Combination; Hemorrhage; Humans; Multicenter Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Ticagrelor; Warfarin

The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens.. Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis.. Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26).. Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Ticagrelor; Warfarin

Several randomized clinical trials (RCTs) have compared the use of dual therapy (DT), or one of the non-vitamin K antagonist oral anticoagulants (NOAC) with a P2Y12 agent, versus triple therapy (TT), consisting of a vitamin-K antagonist (VKA) along with dual antiplatelet therapy, in patients with concomitant atrial fibrillation after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS). We performed a meta-analysis and systematic review of RCTs to evaluate the safety and efficacy of NOAC-based DT in such patients.. The major efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of mortality, myocardial infarction, stroke, stent thrombosis (ST), and urgent revascularization. The International Society on Thrombosis and Hemostasis (ISTH) major or clinically relevant non-major bleeding (CRNM) was the major primary safety outcome.. A total of 4 RCTs were included in the meta-analysis with 7942 total patients for analysis (DT: 4377 & TT: 3565). Compared to TT, DT resulted in similar risk of MACCE (OR: 1.12; 95% CI: 0.94-1.34; P = 0.20) and other efficacy endpoints with a trend in increased risk of ST in the DT group (1.55; 0.99-2.44; P = 0.06). DT resulted in lower risk of ISTH major or CRNM bleeding (0.56; 0.41-0.76; P < 0.01), and all other bleeding outcomes except for a trend of reduced risk of TIMI minor bleeding.. In conclusion, patients with atrial fibrillation who undergo PCI or develop ACS, NOAC-based dual therapy reduces bleeding outcomes without significantly increasing ischemic outcomes. Future trials should explore the possible differences in stent thrombosis.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Warfarin

Vitamin-K antagonists (VKA) have been the standard for oral anticoagulation. However, they carry several problems in older patients: frequent bleeding complications, complex management, risk of interactions with multiple drugs. Two classes of direct oral anticoagulants (DOA) are currently available in France: (a) direct thrombin inhibitors: dabigatran; and (b) direct factor Xa inhibitors: rivaroxaban, apixaban and others. Their management is easier: quickly effective after administration, they are given at fixed doses and do not need regular laboratory monitoring. Several randomized trials have shown that DOA are non-inferior to VKA for treating venous thromboembolic disease (prophylactic or curative treatment) and atrial fibrillation (prevention of associated embolisms). DOA might be also effective for long-term treatment of coronary disease, in some cases. No trial has specifically studied older patients. In the context of atrial fibrillation, subgroup analysis show similar results between patients above and below 75-years-old. Lower doses of dabigatran and apixaban should be used in many older people. All DOA are eliminated at least partly by kidneys. Their dose must be reduced in moderate renal failure (filtration glomerular rate (FGR) 30 to 50mL/min) and they are contraindicated in older patients with severe renal failure (FGR<30mL/min). DOA also have other problems: (a) important drug interactions are still possible, (b) the clinical application of specific coagulation tests need to be defined, (c) their safety in some subgroups of elderly patients, very different from patients included in clinical trials, is not known.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Contraindications, Drug; Dose-Response Relationship, Drug; Drug Interactions; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemorrhage; Humans; Renal Insufficiency, Chronic; Risk Factors; Secondary Prevention; Stroke; Thromboembolism; Vitamin K; Warfarin

The treatment of patients requiring anticoagulation who develop acute coronary syndrome (ACS) and/or require percutaneous coronary intervention (PCI) must balance the reduction in major adverse cardiovascular events, stroke, and major bleeding. The development of direct oral anticoagulants (DOACs) for the treatment of atrial fibrillation has ushered in an era of potential treatment options for these complex patients. PURPOSE OF REVIEW: To review the clinical evidence underlying the use of DOACs for the treatment of patients with atrial fibrillation and ACS or PCI. RECENT FINDINGS: Three trials studied this particular patient population; WOEST showed that dual therapy with warfarin and clopidogrel decreased hemorrhage at 1 year compared with standard triple therapy (19.4 vs. 44.4% HR 0.36; 95% CI 0.26-0.50; P < 0.0001), without increasing thromboembolic events (11.1 vs. 17.6% HR 0.60; 95% CI 0.38-0.94; P = 0.025). PIONEER AF-PCI showed that 10-15 mg rivaroxaban plus P2Y

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin

The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents. The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety. In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Electric Countershock; Fibrinolytic Agents; Heart Valve Diseases; Hemorrhage; Humans; International Normalized Ratio; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Renal Insufficiency; Risk Assessment; Secondary Prevention; Thromboembolism; Thrombophilia; Vitamin K; Warfarin

A comprehensive meta-analysis was performed to investigate whether the combination of high-/low-dose of aspirin and various intensities of warfarin (W) offer greater benefit than aspirin (ASA) alone. A total of 14 randomized clinical trials (RCTs) having 26,916 patients with acute coronary syndrome (ACS) met inclusion criteria. The efficacy and safety of all outcomes which included myocardial infarction (MI), all-cause death, stroke, and bleeding were calculated. The overall outcomes analysis showed there was no significant difference in the risk of MI (relative ratio [RR] 0.959, 95 % confidence interval [CI] 0.78-1.04, P = 0.308), stroke (RR 0.789, 95 % CI 0.57-1.09, P = 0.145), and all-cause death (RR 1.007, 95 % CI 0.93-1.09, P = 0.87) between the combination group and ASA group. The subgroup analysis suggested that ASA (≤100 mg/day) plus W (mean international normalized ratio [INR] 2.0-3.0) decreased the risk rate of stroke (RR 0.660, 95 % CI 0.50-0.87, P = 0.003). There was a lower risk of MI (RR 0.605, 95 % CI 0.47-0.77, P < 0.0001) as well as stroke (RR 0.594, 95 % CI 0.45-0.79, P < 0.0001) between W (INR 2.0-3.0) combined with ASA (mean dose ≥100 mg/day) and ASA. However, the risk of major bleeding (RR 1.738, 95 % CI 1.45-2.08, P < 0.0001) and minor bleeding (RR 2.767, 95 % CI 2.12-3.61, P < 0.0001) was almost doubled in the combined groups. Compared with ASA, high-dose aspirin with moderate-intensity warfarin (INR 2.0-3.0) may better reduce the risk of MI and stroke but confer an increased risk of bleeding.

Topics: Acute Coronary Syndrome; Adult; Aged; Anticoagulants; Aspirin; Causality; Comorbidity; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Male; Middle Aged; Risk Factors; Stroke; Survival Rate; Thromboembolism; Warfarin; Young Adult

The role of thrombin in vascular physiology and pathophysiology continues to impact our understanding of many cellular processes and systems including the function of platelets, endothelial cells, smooth muscle cells, leukocytes and the regulation of the coagulation cascade. Recent acute coronary syndrome clinical trial results that have compared the use of parenteral or oral anticoagulants versus or in combination with anti-platelet agents have forced a reexamination of the importance of thrombin activity in influencing patient outcomes, particularly in the area of secondary prevention. The debate of the need to include oral anticoagulation as a concomitant or replacement therapy to an antiplatelet regimen as a means to improve patient outcomes requires further examination and larger prospective clinical trials.

Topics: Acute Coronary Syndrome; Administration, Oral; Animals; Anticoagulants; Atherosclerosis; Blood Coagulation; Blood Platelets; Cardiovascular Diseases; Clinical Trials as Topic; Fibrinolytic Agents; Humans; Inflammation; Mice; Platelet Aggregation Inhibitors; Receptor, PAR-1; Receptors, Thrombin; Risk Factors; Secondary Prevention; Thrombin; Warfarin

Atrial fibrillation (AF) is associated with an increase in mortality and morbidity, with a substantial increase in stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home than strokes unrelated to AF.. To provide an overview of current concepts and recent developments in stroke prevention in AF, with suggestions for practical management.. A comprehensive structured literature search was performed using MEDLINE for studies published through March 11, 2015, that reported on AF and stroke, bleeding risk factors, and stroke prevention.. The risk of stroke in AF is reduced by anticoagulant therapy. Thromboprophylaxis can be obtained with vitamin K antagonists (VKA, eg, warfarin) or a non-VKA oral anticoagulant (NOAC). Major guidelines emphasize the important role of oral anticoagulation (OAC) for effective stroke prevention in AF. Initially, clinicians should identify low-risk AF patients who do not require antithrombotic therapy (ie, CHA2DS2-VASc score, 0 for men; 1 for women). Subsequently, patients with at least 1 stroke risk factor (except when the only risk is being a woman) should be offered OAC. A patient's individual risk of bleeding from antithrombotic therapy should be assessed, and modifiable risk factors for bleeding should be addressed (blood pressure control, discontinuing unnecessary medications such as aspirin or nonsteroidal anti-inflammatory drugs). The international normalized ratio should be tightly controlled for patients receiving VKAs.. Stroke prevention is central to the management of AF, irrespective of a rate or rhythm control strategy. Following the initial focus on identifying low-risk patients, all others with 1 or more stroke risk factors should be offered OAC.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Percutaneous Coronary Intervention; Risk Factors; Stroke; Warfarin

Antiplatelet and anticoagulant drugs are the mainstay of treatment of acute coronary syndrome (ACS). The last 30 years have seen the development of various agents, a deeper understanding of the pathobiology of this disease, and an evolution in its treatment. We review the role of contemporary agents in ACS and highlight key clinical trials of these agents.

Topics: Acute Coronary Syndrome; Adenosine; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Clopidogrel; Dabigatran; Enoxaparin; Fondaparinux; Heparin; Hirudins; Humans; Morpholines; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Ticagrelor; Ticlopidine; Warfarin

Anticoagulation therapy is one of the most important advances in modern medicine, saving thousands of lives from the complications of atrial fibrillation and mechanical heart valves and preventing recurrent venous thromboembolism. Warfarin and heparins have been the predominant anticoagulants used until the past decade. However, the arrival of newer target-specific anticoagulants has brought us easier and equally effective agents, although no specific antidotes are yet available. Being relatively newer drugs, physicians need to be familiar with the various practical issues that may be encountered with the prescription of these drugs, which are summarised in this review.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Warfarin

Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Anticoagulants; Aspirin; Drug Therapy, Combination; Enoxaparin; Eptifibatide; Fondaparinux; Heparin; Hirudins; Humans; Lactones; Peptide Fragments; Peptides; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Pyridines; Receptors, Thrombin; Recombinant Proteins; Thiophenes; Ticagrelor; Tirofiban; Tyrosine; Warfarin

Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban).

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Clopidogrel; Dabigatran; Hemorrhage; Humans; Morpholines; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Secondary Prevention; Thiophenes; Ticlopidine; Warfarin

Dabigatran 150 mg twice daily was shown to be superior to warfarin in preventing stroke in subjects with nonvalvular atrial fibrillation (SPAF) in the RE-LY (Randomized Evaluation of Long-term anticoagulation therapY) trial. Numerically, more myocardial infarctions occurred in patients receiving dabigatran compared with well-controlled warfarin. This observation prompted a comprehensive analysis of cardiovascular outcomes, including myocardial infarction, in all completed Phase II and III trials of dabigatran etexilate.. The analysis included comparisons of dabigatran with warfarin, enoxaparin, and placebo. Data were analyzed for the occurrence of cardiovascular events from 14 comparative trials (n = 42,484) in five different indications. Individual study data were evaluated, as well as pooled subject-level data grouped by comparator.. In the pooled analysis of individual patient data comparing dabigatran with warfarin (SPAF and venous thromboembolism treatment indications), myocardial infarction occurrence favored warfarin (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.96-1.76 for dabigatran 110 mg twice daily and OR 1.42, 95% CI 1.07-1.88 for dabigatran 150 mg twice daily). The clinically relevant composite endpoint of myocardial infarction, total stroke, and vascular death demonstrated numerically fewer events in dabigatran 150 mg patients (OR 0.87, 95% CI 0.77-1.00), but was similar for dabigatran 110 mg (OR 0.99, 95% CI 0.87-1.13). Dabigatran had similar myocardial infarction rates when compared with enoxaparin or placebo.. These analyses suggest a more protective effect of well-controlled warfarin, but not enoxaparin, compared with dabigatran in preventing myocardial infarction in multiple clinical settings. Dabigatran showed an overall positive benefit-risk ratio for multiple clinically important cardiovascular composite endpoints in all evaluated clinical indications. In conclusion, these data suggest that myocardial infarction is not an adverse drug reaction associated with use of dabigatran.

Topics: Acute Coronary Syndrome; Antithrombins; Atrial Fibrillation; Benzimidazoles; Chi-Square Distribution; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dabigatran; Enoxaparin; Humans; Myocardial Infarction; Odds Ratio; Pyridines; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Venous Thromboembolism; Warfarin

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Risk Assessment; Stroke; Venous Thromboembolism; Warfarin

As acute coronary syndrome (ACS) becomes more common nationwide and current anticoagulation regimens used in patients with ACS continue to possess their shortcomings, the need for new anticoagulants is on the rise. Although heparin and warfarin are used effectively in patients with ACS, they both have significant side effects and delivery issues. New factor Xa inhibitors offer an oral alternative that functions early in the coagulation cascade. The role of these new drugs in ACS is explored here. Electronic search strategies were used to collect reviews, randomized controlled trials, and other studies. Databases used included Medline and Cochrane Library and hand selection. Sources selected were limited to those that discussed factor Xa inhibitors in the context of ACS. Selected studies were then assessed for quality and relevance and those deemed relevant included for analysis. Some of the factor Xa inhibitors such as rivaroxaban offer anticoagulation as effective as, if not more effective, heparin and warfarin with lower risks of bleeding and other adverse effects such as heparin-induced thrombocytopenia. Many of these new agents also come in oral form, making them easy for patients to manage and use daily.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Cyclic N-Oxides; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Morpholines; Naphthalenes; Polysaccharides; Propionates; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Treatment Outcome; Warfarin

Venous thromboembolism (VTE) is a major public health concern since the incidence of VTE rises substantially with age. Furthermore, the diagnosis can be elusive since patients can present differently, causing delay in diagnosis and initiation of treatment and resulting in major morbidity and mortality. In addition to accuracy and precision in diagnosis, antithrombotic therapies are the cornerstones of VTE management. In traditional paradigm, vitamin K antagonists (warfarin), indirect factor Xa inhibitors, and heparin are the foundation in management of VTE. Warfarin has been the only available oral anticoagulant therapy for several decades. Although warfarin is effective in both treatment and prophylaxis against VTE, there are several limitations. Therefore, the novel anticoagulation therapies, including rivaroxaban, apixaban, and dabigatran etexilate, have apparent advantages over warfarin in terms of clinical efficacy and adverse effects. The objective of this review is to describe the background and clinical implications of these novel anticoagulants.

Topics: Acute Coronary Syndrome; Administration, Oral; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K; Warfarin

Acute coronary syndromes (ACS) cause cessation of myocardial blood flow leading to coronary ischemia. The standard medical treatment includes heparin or low molecular weight heparin in the hospital, antiplatelet agents in the hospital and long term, and occasionally warfarin long term. All of these therapies are associated with bleeding complications. Furthermore, warfarin, with its narrow therapeutic window and need for frequent laboratory monitoring, poses several disadvantages. The development of novel oral factor Xa inhibitors and oral direct thrombin inhibitors may provide an alternative to warfarin. In this review, we discuss the new agents, rivaroxaban, apixaban, and dabigatran, for the potential treatment of ACS. We also review the relevant clinical trials evaluating their effects in ACS. These novel anticoagulants allow convenience of use with no requirement for laboratory monitoring and limited drug interactions, which may provide multifaceted treatment options for ACS and anticoagulation in the future.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Antithrombins; Aspirin; Benzimidazoles; beta-Alanine; Clopidogrel; Dabigatran; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Heparin; Humans; Morpholines; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Ticlopidine; Warfarin

The occurrence of disabling stroke, the major fatal consequence of atrial fibrillation, can be reduced by almost two-thirds with warfarin oral anticoagulation. Recent estimates on the prevalence of atrial fibrillation in the USA suggest that approximately 3 million people suffer from this common cardiac arrhythmia, therefore, the socioeconomic impact of adequate oral anticoagulation is enormous. Rivaroxaban, a direct orally available factor Xa inhibitor, is the first of a new class of drugs that target a central factor of the coagulation cascade upstream of thrombin. In the ROCKET AF clinical trial, rivaroxaban demonstrated noninferiority compared with warfarin for stroke prevention in patients with atrial fibrillation, while intracranial and fatal bleeding occurred less frequently with rivaroxaban treatment. Rivaroxban has recently been approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation by the US FDA and EMA. Very recently, rivaroxaban in addition to dual antiplatelet therapy, was shown to reduce mortality in patients with a recent acute coronary syndrome in the ATLAS ACS 2-TIMI 51 clinical trial. The clinical evaluation of rivaroxaban in cardiovascular disease and the results of the ROCKET AF study, the landmark clinical trial of rivaroxaban for stroke prevention, are discussed along with the unique pharmacological profile of rivaroxaban.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Drug Approval; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Warfarin

Patients with acute coronary syndrome (ACS) continue to be at risk for recurrent ischemic events, despite an early invasive strategy and the use of dual antiplatelet therapy. The anticoagulant pathway remains activated for a prolonged period after ACS and, consequently, has been a target for treatment. Early studies with warfarin indicated its benefit, but the risk of bleeding and the complexities of warfarin anticoagulation resulted in little use of this strategy. Rivaroxaban, apixaban, and dabigatran are new specific inhibitors of anticoagulant factors (Xa or IIa) currently available for the prevention of thrombosis and/or thromboembolism. Thus far, studies with dabigatran and apixaban in ACS have shown no clinical benefit and bleeding has been increased. The ATLAS ACS 2-TIMI 51 trial observed the impact of rivaroxaban 2.5 mg and 5 mg twice daily in patients with recent ACS receiving current management (both early invasive strategy and dual antiplatelet therapy with aspirin and clopidogrel) over a follow-up period of over 1 year. Rivaroxaban 2.5 mg twice daily reduced cardiovascular death, myocardial infarction, or stroke by 16%, and both cardiovascular and all-cause mortality by approximately 20%. Although major bleeding increased from 0.6% to 2.1% and intracranial hemorrhage from 0.2% to 0.6%, there was no increase in fatal bleeding. The role of rivaroxaban in the management of ACS is discussed in this review. The reduction in mortality is the main finding that could lead to the use of rivaroxaban in the management of ACS in high-risk individuals with a low bleeding risk.

Topics: Acute Coronary Syndrome; Anticoagulants; Dose-Response Relationship, Drug; Hemorrhage; Humans; Intracranial Hemorrhages; Morpholines; Risk; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis; Warfarin

Antithrombotic therapy plays an essential role in the management of some of the most common and morbid medical conditions. Triple oral antithrombotic therapy (TOAT) is defined as the administration of both therapeutic oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT) to patients with indications for both treatments. The current societal guidelines regarding TOAT are derived from observational studies and some trials of the use of warfarin in addition to antiplatelet therapy in patients with atrial fibrillation and a recent acute coronary syndrome or percutaneous coronary intervention. The general apprehension to administer TOAT is due to the heightened concern for bleeding, rendering warfarin's pharmacokinetic properties concerning. Newer anticoagulant agents may serve as appealing alternatives, and further investigations are warranted. The results of the recent trials that have studied the use of these agents in atrial fibrillation and acute coronary syndrome offer some useful applications to TOAT. Ultimately, selecting the most favorable antithrombotic strategy is going to involve weighing the risks and benefits for each patient.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Fibrinolytic Agents; Hematology; Humans; Platelet Aggregation Inhibitors; Recurrence; Risk; Stroke; Thromboembolism; Thrombosis; Treatment Outcome; Warfarin

The use of triple therapy (warfarin plus dual antiplatelet therapy) has increased in recent years due to an aging population with a higher risk for atrial fibrillation, as well as the increased use of coronary stents for acute coronary syndromes. Triple therapy confers a higher bleeding risk than either warfarin or dual antiplatelet therapy alone. However, warfarin alone is inadequate for patients with indications for triple therapy because of an unacceptable risk of stent thrombosis, and dual antiplatelet therapy is inferior to warfarin for the prevention of ischemic strokes in patients with atrial fibrillation, mechanical valves, or intraventricular thrombosis. Hospitalists face the challenge of balancing the aforementioned risks; the optimal management of these patients requires knowledge of the relevant literature and expertise. In this paper, we review the current literature on antiplatelet and anticoagulant combinations in patients with atrial fibrillation and coronary stents in order to improve adherence to published guidelines and to reduce the risk of bleeding.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Hospitalization; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticlopidine; Warfarin

The combination of 2 antiplatelet agents and warfarin may be beneficial to a select group of patients, but its use remains controversial. Here's why.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Patient Selection; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticlopidine; Warfarin

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

Arterial and venous thromboembolism account for significant morbidity and mortality worldwide. Warfarin, and other vitamin K antagonists (VKAs), have been the only class of oral anticoagulants currently in clinical use and have been so for over 50 years. Although warfarin is effective in preventing thromboembolism, its use is limited by its narrow therapeutic index that necessitates frequent monitoring and dose adjustments resulting in considerable inconvenience to patients and clinicians. There are now several orally administered anticoagulants in late stages of clinical development that may offer effective, safer, and more convenient anticoagulation. This review summarizes and compares data on novel anticoagulants in the prophylaxis and treatment of venous thromboembolism, acute coronary syndromes, and the prevention of stroke in patients with atrial fibrillation.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Stroke; Thrombin; Thromboembolism; Vitamin K; Warfarin

The article concerns the policy of anti-platelet treatment in patients with coronary heart disease exposed to transcutaneous coronary interventions. Patients with cardiac fibrillations are specially considered. International trials are reviewed.

Topics: Acute Coronary Syndrome; Anticoagulants; Arrhythmias, Cardiac; Contraindications; Coronary Angiography; Coronary Occlusion; Coronary Thrombosis; Disease Progression; Humans; Randomized Controlled Trials as Topic; Stents; Vitamin K; Warfarin

Rivaroxaban is a small molecule, direct Factor Xa inhibitor and may be a potentially attractive alternative to vitamin K antagonists. Rivaroxaban is being investigated for the prevention and treatment of venous and arterial thrombosis. A broad search of Medline, clinicaltrials.gov and the annual proceedings of the American Society of Hematology and the International Society on Thrombosis and Hemostasis was conducted. This review addresses the findings of this systematic search, including the need for new oral anticoagulants, the development and pharmacology of rivaroxaban, and the results of completed as well as ongoing trials with rivaroxaban. At present, the safety and efficacy of rivaroxaban for the prophylaxis and treatment of venous thromboembolism has been evaluated in Phase II and Phase III trials involving over 24,000 patients. Additionally, rivaroxaban is being evaluated for the treatment of pulmonary embolism, secondary prevention after acute coronary syndromes and the prevention of stroke and non-central nervous system embolism in patients with non-valvular atrial fibrillation. The drug may have its greatest impact in providing a much-needed and attractive alternative to warfarin. Further data (especially large Phase III trials) are required.

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Aged, 80 and over; Animals; Anticoagulants; Atrial Fibrillation; Binding Sites; Clinical Trials as Topic; Comorbidity; Drug Evaluation, Preclinical; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Rats; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Warfarin

Data are limited regarding the risk of cerebrovascular ischemic events and major bleeding in patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI).. Determine the efficacy and safety of apixaban or vitamin K antagonists (VKA) and aspirin or placebo according to prior stroke, transient ischemic attack (TIA), or thromboembolism (TE).. In this prospective, multicenter, 2-by-2 factorial, randomized clinical trial, post hoc parallel analyses were performed to compare randomized treatment regimens according to presence or absence of prior stroke/TIA/TE using Cox proportional hazards models. Patients with AF, recent ACS or PCI, and planned use of P2Y12 inhibitors for 6 months or longer were included; 33 patients with missing data about prior stroke/TIA/TE were excluded.. Apixaban (5 mg or 2.5 mg twice daily) or VKA and aspirin or placebo.. Major or clinically relevant nonmajor (CRNM) bleeding.. Of 4581 patients included, 633 (13.8%) had prior stroke/TIA/TE. Patients with vs without prior stroke/TIA/TE were older; had higher CHA2DS2-VASC and HAS-BLED scores; and more frequently had prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Apixaban was associated with lower rates of major or CRNM bleeding and death or hospitalization than VKA in patients with (hazard ratio [HR], 0.69; 95% CI, 0.46-1.03) and without (HR, 0.68; 95% CI, 0.57-0.82) prior stroke/TIA/TE. Patients without prior stroke/TIA/TE receiving aspirin vs placebo had higher rates of bleeding; this difference appeared less substantial among patients with prior stroke/TIA/TE (P = .01 for interaction). Aspirin was associated with numerically lower rates of death or ischemic events than placebo in patients with (HR, 0.71; 95% CI, 0.42-1.20) and without (HR, 0.93; 95% CI, 0.72-1.21) prior stroke/TIA/TE (not statistically significant).. The safety and efficacy of apixaban compared with VKA was consistent with the AUGUSTUS findings, irrespective of prior stroke/TIA/TE. Aspirin increased major or CRNM bleeding, particularly in patients without prior stroke/TIA/TE. Although aspirin may have some benefit in patients with prior stroke, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status.. ClinicalTrials.gov Identifier: NCT02415400.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Attack, Transient; Percutaneous Coronary Intervention; Prospective Studies; Pyrazoles; Pyridones; Stroke; Thromboembolism; Warfarin

To evaluate efficacy of antithrombotic agents in critically ill patients with elevated troponin I level during intensive care unit (ICU) admission.. It was a retrospective observational study which was conducted in a tertiary teaching hospital in Taipei, Taiwan. All patients hospitalized in ICU for >3 days and with available serum troponin I data from December 2015 to July 2017 were included. Patients with definite diagnosis of acute myocardial infarction (AMI) were excluded. We divided patients with troponin I elevation into three groups; no prescription, chronic prescription and new prescription of antithrombotic agents during ICU admission. We defined new prescription when patients were on antithrombotic agents, including antiplatelet agents, direct oral anticoagulants, and warfarin after troponin I was found to be elevated at ICU admission and chronic prescription, if antithrombotic agents were on medication list more than 30 days before ICU admission. Primary outcomes were 30-day and one-year all-cause mortality. Of 597 subjects who met inclusion criteria, 407 (68%) patients had elevated troponin I (>0.1 ng/mL) on ICU admission. These patients had increased 30-day [hazard ratio (HR), 1.679; 95% confidence interval (CI), 1.132-2.491; p = 0.009] and one-year (HR, 1.568; 95% CI, 1.180-2.083; p = 0.002) all-cause mortality compared with those without elevated troponin I. In patients with elevated troponin I, there was no significant difference of 30-day all-cause mortality among three groups (p = 0.051) whereas patients on chronic prescription showed significant survival benefit in one-year all-cause mortality when compared to those without or with new prescription (p = 0.008).. In critically ill patients, elevated troponin I in the absence of AMI was associated with poor prognosis. Newly prescribed antithrombotic agents in ICU didn't reveal the difference in short and long-term prognosis while chronic antithrombotic agent use was associated with better one-year survival rate, suggesting that these drugs play a protective role in this high-risk population.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Critical Illness; Disease-Free Survival; Female; Fibrinolytic Agents; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Retrospective Studies; Survival Rate; Troponin I; 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

The optimal antithrombotic strategy for patients with atrial fibrillation (AF) who develop acute coronary syndrome (ACS) and/or the need for percutaneous coronary intervention (PCI) is uncertain. The risk of bleeding is a major concern when oral anticoagulation is required to prevent stroke, and concomitant therapy with antiplatelet agents is required to minimize recurrent ischemic events.. AUGUSTUS is an international, multicenter randomized trial with a 2 × 2 factorial design to compare apixaban with vitamin K antagonists and aspirin with placebo in patients with AF who develop ACS and/or undergo PCI and are receiving a P2Y12 inhibitor. Patients will be evaluated for eligibility during their ACS and/or PCI hospitalization. The primary outcome is the composite of major and clinically relevant nonmajor bleeding defined by the International Society on Thrombosis and Haemostasis. A key secondary outcome is the composite of all-cause death and all-cause hospitalization. Other secondary objectives are to evaluate ischemic outcomes including the composite of death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and all-cause hospitalization and each individual component. The aim is to enroll approximately 4,600 patients from around 500 sites in 33 countries.. AUGUSTUS will provide insight into the optimal oral antithrombotic therapy strategy for patients with AF and concomitant coronary artery disease. The unique 2 × 2 factorial design will delineate the bleeding effects of various anticoagulant and antiplatelet therapies and generate evidence to guide the selection of the optimal antithrombotic regimen for this challenging group of patients. It is the largest and only prospective randomized trial to investigate in a blinded fashion the risk and benefits of aspirin on top of a non-vitamin K antagonist oral anticoagulant and P2Y12 receptor inhibition.

Topics: Acute Coronary Syndrome; Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Selection; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Risk Factors; Stroke; Treatment Outcome; Warfarin

Use of proton pump inhibitor (PPI) reduces the risk of gastrointestinal (GI) bleeding, and is generally recommended for high GI risk patients taking nonsteroidal anti-inflammatory agents. Aspirin and/or anticoagulants have been identified as increasing the risk of GI bleeding, whereby use of PPI could reduce this risk. The use of PPI in routine practice is not well defined, especially in patients with acute coronary syndromes (ACS) who require one or several antithrombotic drugs.. We analyzed the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial database, which enrolled patients who had been hospitalized for ACS. Patients were to be treated with aspirin, and received clopidogrel and/or warfarin at the discretion of the treating physician. We analyzed the use of PPI at baseline, which was not specified in the protocol, according to prior known GI risk factors.. Of the 4162 patients enrolled, 781 (18.8%) received PPI during the course of this study. The use ranged from 14% to 67% across the number of GI risk factors of 0 to > or =4 (P < 0.0001). Individual factors most associated with increased use of PPI were a prior GI event (RR = 2.3, P < 0.001) and use of anticoagulants (RR = 1.49, P < 0.001), but not dual antiplatelet therapy.. Use of PPI following ACS is modest, although it did increase with an increasing number of previously identified GI risk factors. Further, larger studies are warranted to validate prior, or identify new, risk factors as predictors of long-term bleeding, and improve awareness of GI bleeding risk such that use of PPI could be optimized.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Clopidogrel; Female; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Proton Pump Inhibitors; Risk Factors; Ticlopidine; Treatment Outcome; Warfarin

We constructed a cost-effectiveness model to assess the clinical and economic value of a CDS alert program that provides pharmacogenomic (PGx) testing results, compared to no alert program in acute coronary syndrome (ACS) and atrial fibrillation (AF), from a health system perspective. We defaulted that 20% of 500,000 health-system members between the ages of 55 and 65 received PGx testing for CYP2C19 (ACS-clopidogrel) and CYP2C9, CYP4F2 and VKORC1 (AF-warfarin) annually. Clinical events, costs, and quality-adjusted life years (QALYs) were calculated over 20 years with an annual discount rate of 3%. In total, 3169 alerts would be fired. The CDS alert program would help avoid 16 major clinical events and 6 deaths for ACS; and 2 clinical events and 0.9 deaths for AF. The incremental cost-effectiveness ratio was $39,477/QALY. A PGx-CDS alert program was cost-effective, under a willingness-to-pay threshold of $100,000/QALY gained, compared to no alert program.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Cost-Benefit Analysis; Decision Support Systems, Clinical; Humans; Markov Chains; Middle Aged; Pharmacogenetics; Quality-Adjusted Life Years; Vitamin K Epoxide Reductases; Warfarin

Direct oral anticoagulants (DOACs) are replacing warfarin for stroke prevention in patients with atrial fibrillation (AF).. To assess the effectiveness and safety of concomitant treatment with antiplatelet-DOAC compared to antiplatelet-warfarin in patients with acute coronary syndrome (ACS) and AF.. Retrospective propensity score-matched cohort study using United States-based commercial healthcare database from January 2016 to June 2019.. New-users of antiplatelet-DOAC and antiplatelet-warfarin who initiated the combined therapy within 30 days following incident ACS diagnosis.. Primary study outcomes were recurrent cardiovascular diseases (CVD) (ie, a composite of stroke and myocardial infarction) and major bleeding events identified via discharge diagnoses. We controlled for potential confounders via propensity score matching (PSM). We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar time.. After PSM, a total of 2,472 persons were included (1,236 users of antiplatelet-DOAC and 1,236 users of antiplatelet-warfarin). The use of antiplatelet-DOAC (vs. antiplatelet-warfarin) was associated with a reduced rate of recurrent CVD (adjusted HR 0.72, 95% confidence interval [CI], 0.56-0.92) and major bleeding events (adjusted HR, 0.49, 95% CI 0.33-0.72).. Residual confounding.. In real-world data of AF patients with concurrent ACS, the use of antiplatelet-DOAC following ACS diagnosis was associated with a lower rate of recurrent CVD and major bleeding events compared with antiplatelet-warfarin. These findings highlight a potential promising role for DOACs in patients with ACS and AF requiring combined antiplatelet therapy.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Retrospective Studies; United States; Warfarin

Time in therapeutic range (TTR) assesses the safety and effectiveness of warfarin therapy using the international normalised ratio. This study investigated the TTR in Hong Kong patients using both European and Japanese therapeutic ranges and patients' economic and clinical outcomes. Predictors of poor warfarin control and patient knowledge concerning warfarin therapy were assessed.. A 5-month observational study with retrospective and prospective components was conducted in the Prince of Wales Hospital. The study examined electronic patient records of patients who received warfarin for at least 1 year during the period from January 2010 to August 2015. Patient knowledge was assessed via phone interview using the Oral Anticoagulation Knowledge (OAK) test.. In total, 259 patients were included; 174 completed the OAK test. The calculated mean TTR was 40.2±17.1% (European therapeutic range), compared with 49.1±16.1% (Japanese therapeutic range) [P<0.001]. Mean TTR was higher in patients with atrial fibrillation than in patients with prosthetic heart valve (P<0.001). The abilities of TTR to predict clinical and economic outcomes were comparable between European and Japanese therapeutic ranges. Patients with ideal TTR had fewer clinical complications and lower healthcare costs. Patients with younger age exhibited worse TTR, as did those with concurrent use of furosemide, famotidine, or simvastatin. Mean OAK test score was 54.1%. Only 24 (13.8%) patients achieved a satisfactory overall score of ≥75% in the test.. Warfarin use in Hong Kong patients was poorly controlled, regardless of indication. Patient knowledge concerning warfarin use was suboptimal; thus, additional patient education is warranted regarding warfarin.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Atrial Fibrillation; Female; Health Care Costs; Health Knowledge, Attitudes, Practice; Hong Kong; Humans; International Normalized Ratio; Male; Middle Aged; Patient Acceptance of Health Care; Prospective Studies; Retrospective Studies; Time Factors; Treatment Outcome; 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

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

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1β-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.

Topics: Acute Coronary Syndrome; Anti-Inflammatory Agents; Anticoagulants; Arrhythmias, Cardiac; Aspirin; Atrial Fibrillation; Cardiovascular System; Comorbidity; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Interleukin-1beta; Models, Theoretical; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stents; Stroke; Warfarin

Dual antiplatelet therapy (DAPT) varies after placement of drug-eluting stents (DES) in patients presenting with acute coronary syndromes (ACS). Our aim was to study patient characteristics and predictors of switching, in-hospital or at discharge, from clopidogrel (CLO) to ticagrelor (TIC) or vice versa.. The study population included patients with ACS who had DES and initially received either CLO or TIC between January 2011 and December 2017. Patients were divided into 4 groups based on initial DAPT choice and whether DAPT was switched in-hospital or during discharge. Clinical outcomes of interest were bleeding events, need for anticoagulation, and need for in-hospital coronary artery bypass graft (CABG).. We identified 2837 patients who received DES and started on DAPT. DAPT switch from 1 P2Y12 inhibitor to another occurred in 9%, either in-hospital or at discharge. Of 1834 patients started on CLO, 112 were switched to TIC. Of 1003 patients started on TIC, 142 were switched to CLO. The need for in-hospital CABG was 7.8% in the TIC-CLO group compared to none in the CLO-TIC group (p = 0.002). Adjusted for covariates, the TIC-CLO group was 3 times more likely to need anticoagulation with warfarin than the CLO-CLO group (p < 0.001) and over 5 times more likely than the CLO-TIC group and the TIC-TIC group (p < 0.005 for both).. Switching from 1 generation P2Y12 inhibitor to another does occur in ACS patients. Clinical needs such as in-hospital CABG or oral anticoagulation upon discharge are real and dictate the switch from TIC to CLO.. A single-center observational study of 2837 patients with acute coronary syndromes treated with drug-eluting stents found that some do get switched from one generation P2Y12 inhibitor to another. The switch from clopidogrel to ticagrelor is driven by clinical needs such as in-hospital coronary artery bypass grafting or the need for oral anticoagulation upon discharge.

Topics: Acute Coronary Syndrome; Aged; Antithrombins; Drug Substitution; Drug-Eluting Stents; Female; Follow-Up Studies; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Retrospective Studies; Thrombolytic Therapy; Treatment Outcome; Warfarin

BACKGROUND Coronary artery embolization is an exceedingly rare cause of myocardial infarction, but a few cases in association with prosthetic mechanical valves have been reported. We report a case of embolic myocardial infarction caused by a thrombus in the left atrium with deranged coagulation profile in a patient with critical mitral stenosis under warfarinization. CASE REPORT A 22-year-old woman was taken to the catheterization lab for early coronary intervention in lieu of non-ST elevation myocardial infarction. Electrocardiography showed T↓ in V1 to V4, and atrial fibrillation with controlled ventricular rate. Coronary angiography showed total occlusion of the mid-left anterior descending artery with thrombus. After upstream treatment with tirofiban, the apparent thrombus was dislodged distally while passing a BMW wire. No abnormalities were seen by intravascular ultrasound study. Echocardiography revealed critical mitral stenosis, and left atrial clot with mild left ventricular dysfunction. Coagulation profile revealed sub-therapeutic international normalized ratio levels. The sequential angiographic images, normal intravascular ultrasound study, and presence of atrial fibrillation are confirmatory of coronary embolism as the cause of myocardial infarction. Anticoagulation and treatment of acute coronary syndrome were initiated and she was referred for closed mitral valvulotomy. CONCLUSIONS Coronary artery thromboembolism as a nonatherosclerotic cause of acute coronary syndrome is rare. The treatment consists of aggressive anticoagulation, antiplatelet therapy, and interventional options, including simple wiring when possible. In this context, primary prevention in the form of patient education on optimal anticoagulation with oral vitamin K antagonist and medical advice about imminent thromboembolic risks are of extreme importance.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Coronary Occlusion; Coronary Vessels; Electrocardiography; Female; Humans; Mitral Valve Stenosis; Thromboembolism; Warfarin; Young Adult

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

Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS).. We identified all ACS patients on DT upon discharge from Helsingborg Hospital and Skåne University Hospital in Malmö and Lund, Sweden, during 2013. Patients on DT were compared with historical controls discharged with TT. Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for three months.. In total, 107 DT patients were identified and compared with 159 controls on TT. Mean HAS-BLED bleeding risk score and duration of treatment were similar between the groups (HAS-BLED 2.2+/-0.8 vs 2.2+/-1.0 units, p=NS; duration 2.7+/-0.8 vs 2.5+/-0.9months, p=NS; DT vs TT). The incidence of spontaneous major bleeding was similar between the groups, as was a composite of all thrombotic events, i.e. peripheral embolism, stroke/TIA and acute coronary syndrome (bleeding 8/106 (7.5%) vs 11/157 (7.0%), p=NS; thrombosis 5/106 (4.7%) vs 5/157 (3.2%), p=NS; DT vs TT).. Rates of thrombotic and bleeding events were similar in patients with TT and patients with ticagrelor and warfarin.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Thrombosis; Ticagrelor; Ticlopidine; Treatment Outcome; Warfarin

Warfarin is the most widely prescribed anticoagulant drugs. Cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase-oxidaxe complex subunit 1 (VKORC1) contribute significantly to the variability of warfarin dose requirements among patients. We investigated the impact of CYP2C9 and VKORC1 polymorphisms on the variability of warfarin dosage requirements in Egyptian patients with acute coronary syndrome and their association with other nongenetic factors. Eighty participants with acute coronary syndrome were enrolled in this cross-sectional study. Associations between CYP2C9 and VKORC1 gene variants together with daily warfarin dose, demographic data, clinical status of patients and time to target international normalized ratio were assessed. Mean warfarin dose among patients with wild-type CYP2C91/1 genotype was significantly higher than heterozygous CYP2C91/2 and CYP2C91/3 variants (P ≤ 0.001). Patients with wild VKORC1 (G/G) genotype were treated with significantly higher daily warfarin dosages than homozygous (A/A) and heterozygous (G/A) genotypes. Patients carrying VKORC1 (G/G) genotype in combination with the CYP2C91/1 type alleles had the highest daily warfarin dosage, whereas the lowest daily warfarin dosage to achieve the required clinical effect was found among patients having CYP2C91/2 and CYP2C91/3 genotypes combined with VKORC1 (A/A) genotype (P ≤ 0.001). Regression analysis revealed that age, height, CYP2C9 and VKORC1 genotypes were significantly associated with warfarin dose. Genetic polymorphisms in VKORC1, CYP2C9 along with age and height are determinants of warfarin dose requirements in Egyptian population acute coronary syndrome. Higher warfarin loading dose is required for both wild CYP2C9 and VKORC1 gene variants which may contribute to warfarin-resistant cases.

Topics: Acute Coronary Syndrome; Adult; Anticoagulants; Cross-Sectional Studies; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic; Vitamin K Epoxide Reductases; Warfarin; Young Adult

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Atrial Fibrillation; Clopidogrel; Coronary Angiography; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Stents; Ticlopidine; Warfarin

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

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

Clinical experiences have suggested that East Asians show the higher risk of warfarin-related intracranial hemorrhage compared with Westerners. Therefore, different target of the International Normalized Ratio (INR) in East Asians (1.6-2.6) has been proposed and adapted in clinical practice. In terms with antiplatelet therapy, recent evidence has supported the concept of "therapeutic level of platelet reactivity" to balance clinical efficacy and safety in patients undergoing percutaneous coronary intervention (PCI) or those with acute coronary syndrome (ACS). In line with the warfarin experiences, multiple clinical and pharmacodynamic data from East Asians have shown their different therapeutic level of platelet reactivity following PCI or ACS ("East Asian Paradox"). Furthermore, like most cardiovascular drugs, P2Y12 receptor blockers have marked interethnic differences in the pharmacokinetics and pharmacodynamics. The currently performed clinical trials evaluating the clinical efficacy and safety of potent P2Y12 inhibitors mostly don't include enough number of East Asians to draw reliable conclusions. Therefore, dedicated research and guideline(s) for East Asians are required before we can apply Western recommendations for potent P2Y12 inhibitors in East Asian population. It is a time to consider the paradigm shift from "one-guideline-fits-all races" to "race-tailored antiplatelet therapy" in treating ACS patients.

Topics: Acute Coronary Syndrome; Asia, Eastern; Asian People; Blood Platelets; Clopidogrel; Drug Administration Schedule; Evidence-Based Medicine; Female; Guideline Adherence; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticlopidine; Treatment Outcome; Warfarin

This study was planned to compare the clinical characteristics and outcome of patients on warfarin treatment for atrial fibrillation (AF) undergoing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI).. This is a retrospective analysis of 121 patients who underwent isolated CABG and 301 patients who underwent PCI.. PCI patients were older (mean age, 72.9 versus 69.8 years) and more often had prior cardiac surgery (15.9% versus 1.7%) and acute coronary syndrome (53.8% versus 21.5%). CABG patients more often had two- and three-vessel disease (95.0% versus 60.2%) and left main stenosis (32.2% versus 7.0%). The 30-day outcome was similar after PCI and CABG. At 3 years, PCI was associated with lower overall survival (72.0% versus 86.4%, P = 0.006), freedom from repeat revascularization (85.3% versus 98.2%, P < 0.001), freedom from myocardial infarction (83.4% versus 93.8%, P = 0.008), and freedom from major cardiovascular events (57.4% versus 78.9%, P < 0.001). Propensity score adjusted analysis showed that PCI was associated with increased risk of all-cause mortality (P = 0.016, RR 2.166, CI 1.155-4.060), myocardial infarction (P = 0.017, RR 3.161, 95% CI 1.227-8.144), repeat revascularization (P = 0.001, RR 13.152, 95% CI 2.799-61.793), and major cardiac and cerebrovascular complications (P = 0.001, RR 2.347, 95% CI 1.408-3.914). There was no difference in terms of stroke and bleeding episodes at any time point.. In clinical practice, PCI is the preferred revascularization strategy in these frail patients. Patients selected for CABG have a relatively low operative risk and better mid-term outcome in spite of warfarin treatment. The poor prognosis after PCI may mainly reflect frequent co-morbidities in this patient group.

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Coronary Artery Bypass; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prognosis; Retrospective Studies; Stroke; Survival Rate; Treatment Outcome; Warfarin

The in-hospital management of patients on warfarin undergoing coronary stent implantation (PCI-S) is variable, and the in-hospital outcome incompletely defined. To determine the adherence to the current recommendations, and the incidence of adverse events, we carried out the prospective, multicenter, observational WARfarin and coronary STENTing (WAR-STENT) registry (ClinicalTrials.gov identifier NCT00722319). All consecutive patients on warfarin undergoing PCI-S at 37 Italian centers were enrolled and followed for 12 months. Outcome measures were: major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, need for urgent revascularization, stroke, and venous thromboembolism, and major and minor bleeding. In this paper, we report the in-hospital findings. Out of the 411 patients enrolled, 92% were at non-low (ie, moderate or high) thromboembolic risk. The radial approach and bare-metal stents were used in 61% and 60% of cases, respectively. Drug-eluting stents were essentially reserved to patients with diabetes, which in turn, significantly predicted the implantation of drug-eluting stents (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.29-3.17; P=.002). The in-hospital MACE and major bleeding rates were 2.7% and 2.1%, respectively. At discharge, triple therapy (TT) of warfarin, aspirin, and clopidogrel was prescribed to 76% of patients. Prescription of TT was significantly more frequent in the non-low thromboembolic risk group. Non-low thromboembolic risk, in turn, was a significant predictor of TT prescription (OR, 11.2; 95% CI, 4.83-26.3; P<.0001). In conclusion, real-world warfarin patients undergoing PCI-S are largely managed according to the current recommendations. As a consequence, the risk of in-hospital MACE and major bleedings appears limited and acceptable.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Disease Management; Drug-Eluting Stents; Female; Humans; Incidence; Inpatients; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Prospective Studies; Registries; Retrospective Studies; Risk Factors; Stents; Stroke; Thromboembolism; Warfarin

Topics: Acute Coronary Syndrome; Adenosine; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Male; Platelet Aggregation Inhibitors; Ticagrelor; Warfarin

Topics: Acute Coronary Syndrome; Anticoagulants; Aortic Dissection; Coronary Aneurysm; Coronary Angiography; Electrocardiography; Female; Humans; International Normalized Ratio; Middle Aged; Predictive Value of Tests; Treatment Outcome; Warfarin

Patients with nephrotic syndrome are at risk of developing thrombosis in both veins and arteries. Various manifestations in different organs have been reported. Thrombi in heart seen, associated with multiorgan thrombosis have been reported on autopsy earlier, but only once in a living patient with nephrotic syndrome. Here, we report a 13 years old boy with steroid-resistant nephrotic syndrome, who developed an asymptomatic but potentially hazardous large intracardiac thrombus. The child developed nephrotic syndrome at the age of 9 years and had multiple recurrences. At the age of 13 years, he developed myocardial infarction (MI) due to embolism from a large intracardiac thrombus. Later on, he was treated with heparin and warfarin anticoagulation.

Topics: Acute Coronary Syndrome; Adolescent; Adrenal Cortex Hormones; Anterior Wall Myocardial Infarction; Anticoagulants; Coronary Angiography; Coronary Thrombosis; Disease Progression; Echocardiography, Doppler; Electrocardiography; Follow-Up Studies; Heparin; Humans; Male; Nephrotic Syndrome; Rare Diseases; Recurrence; Risk Assessment; Severity of Illness Index; Treatment Outcome; Warfarin

The aim of this study was to evaluate the prevalence of triple antithrombotic therapy (TT) (warfarin, aspirin and clopidogrel) in patients following an acute coronary syndrome (ACS), the bleeding risk compared to double antiplatelet therapy (DAPT) (aspirin and clopidogrel) and evaluate the accuracy of the HAS-BLED risk score in predicting serious bleeding events in TT patients.. We retrospectively identified all ACS patients on TT upon discharge from the Coronary Care Unit at Skane University Hospital between 2005 and 2010. TT patients were compared to age- and sex-matched control patients discharged with DAPT. Major bleeding was defined in accordance with the HAS-BLED derivation study. A total of 2,423 patients were screened, of whom 159 (6.6%) were on TT. The mean age was 67.2 (±0.9) years. The most common indication for TT was atrial fibrillation (n=63, 39.6%) followed by apical akinesia (n=60, 37.8%), and the mean duration of TT was 3.7 (±0.3) months. Upon termination of TT, warfarin was discontinued in 82 (52.2%) patients and clopidogrel in 57 (36.3%) patients. The cumulative incidence of spontaneous bleeding events was significantly higher with TT compared to DAPT at one year (10.2% vs. 3.2%; p=0.01). The HAS-BLED score significantly predicted spontaneous bleeding events in TT patients (area under the receiver operating characteristic [ROC] curve 0.67; 95% CI=0.54-0.79; p=0.048).. TT was relatively common following acute coronary syndrome and was associated with a threefold increase in major bleeding compared to DAPT at one year. The HAS-BLED risk score predicted bleeding events with moderate accuracy.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Aspirin; Chi-Square Distribution; Clopidogrel; Comorbidity; Decision Support Techniques; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Sweden; Ticlopidine; Treatment Outcome; Warfarin

Dual antiplatelet therapy (acetylsalicylic acid and a thienopyridine) is essential after coronary stent implantation, and in the treatment of acute coronary syndrome. Many patients also need oral anticoagulation. Unfortunately, there are no prospective randomised trials to guide therapy. Triple antithrombotic therapy with acetylsalicylic acid, clopidogrel and warfarin is most commonly used. This regimen can reduce the risk of thrombosis and thromboembolism, but is associated with an increased risk of bleeding. Measures that reduce the risk of complications are reduction of INR with careful monitoring, a short duration of triple therapy (when possible) and use of radial access and a bare metal stent.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Hemorrhage; Humans; International Normalized Ratio; Platelet Aggregation Inhibitors; Risk Factors; Stents; Thrombosis; Warfarin

We examined warfarin use at discharge (according to Congestive heart failure, Hypertension, Age>75 years, Diabetes, Prior Stroke/transient ischemic attack score and bleeding risk) and its association with 6-month death or myocardial infarction in patients with post-acute coronary syndrome atrial fibrillation.. Of the 23,208 patients enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network A, and Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors trials, 4.0% (917 patients) had atrial fibrillation as an in-hospital complication and were discharged alive. Cox proportional hazards models were performed to assess 6-month outcomes after discharge.. Overall, 13.5% of patients with an acute coronary syndrome complicated by atrial fibrillation received warfarin at discharge. Warfarin use among patients with atrial fibrillation had no relation with estimated stroke risk; similar rates were observed across Congestive heart failure, Hypertension, Age>75 years, Diabetes, Prior Stroke/transient ischemic attack (CHADS(2)) scores (0, 13%; 1, 14%; > or = 2, 13%) and across different bleeding risk categories (low risk, 11.9%; intermediate risk, 13.3%; high risk, 11.1%). Among patients with in-hospital atrial fibrillation, warfarin use at discharge was independently associated with a lower risk of death or myocardial infarction within 6 months of discharge (hazard ratio 0.39; 95% confidence interval, 0.15-0.98).. Warfarin is associated with better 6-month outcomes among patients with atrial fibrillation complicating an acute coronary syndrome, but its use is not related to CHADS(2) score or bleeding risk.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Fibrinolytic Agents; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Treatment Outcome; Warfarin

Evidence regarding the use of dual antiplatelet therapy and oral anticoagulation (i.e., triple therapy) in acute coronary syndromes (ACS) is limited. We evaluated the characteristics associated with the choice of triple therapy in ACS. Using the Get With The Guidelines (GWTG) Coronary Artery Disease national registry, we studied patients with ACS at 361 sites in the United States from 2004 to 2007. Both univariate analysis and multivariate logistic regression analysis were used to assess the factors associated using triple therapy on discharge. The Generalized Estimating Equation method was used to account for within-hospital clustering in modeling. A total of 86,304 patients presented with ACS during the study period. At discharge, 3,933 patients (4.6%) were prescribed triple therapy, 60,716 patients (70.4%) received dual antiplatelet therapy, 2,348 patients (2.7%) received single antiplatelet therapy plus oral anticoagulation, 19,065 patients (22.1%) received antiplatelet monotherapy, and 242 patients (0.3%) received oral anticoagulation alone. Patients with a history of atrial fibrillation (odds ratio 7.01, 95% confidence interval 6.06 to 8.12; p <0.001), documented new-onset atrial fibrillation (odds ratio 3.76, 95% confidence interval 2.87 to 4.93; p <0.001), or history of atrial flutter (odds ratio 3.38, 95% confidence interval 2.15 to 5.32; p <0.001) were more frequently discharged with triple therapy. In conclusion, for patients with ACS, atrial fibrillation and atrial flutter were most strongly associated with the use of triple therapy; however, this therapy was used less often than dual or single antiplatelet therapy.

Topics: Acute Coronary Syndrome; Aged; Anemia; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Atrial Flutter; Clopidogrel; Diabetes Mellitus; Drug Therapy, Combination; Drug Utilization; Female; Humans; Logistic Models; Male; Middle Aged; Patient Discharge; Platelet Aggregation Inhibitors; Registries; Smoking; Stents; Stroke; Stroke Volume; Ticlopidine; United States; Warfarin

Topics: Acute Coronary Syndrome; Anticoagulants; Coronary Angiography; Coronary Thrombosis; Humans; Male; Platelet Aggregation Inhibitors; Risk Factors; Smoking; Stents; Warfarin; Young Adult

The optimal antithrombotic therapy strategy for atrial fibrillation (AF) patients who undergo percutaneous coronary intervention with stent implantation (PCI-S) is unknown. We assessed the safety of antithrombotic therapy strategies in AF patients with indication for oral anticoagulation (OAC) undergoing PCI-S.. We studied consecutive AF patients with indication for OAC who underwent PCI-S. We compared patients that received triple antithrombotic therapy (TT) [aspirin, clopidogrel, and coumadin] against other regimes (non-TT) after PCI-S. The primary end point was defined as the occurrence of major bleeding complications that were termed as early major bleeding (EMB) [< or = 48 h] or late major bleeding (LMB) [> 48 h]. Clinical follow-up was performed, and complications were recorded.. We studied 104 patients (mean age +/- SD, 72 +/- 8 years; 70% men); TT was used in 51 patients (49%). TT was associated with a higher incidence of LMB (21.6% vs non-TT, 3.8%; p = 0.006) but not of EMB (5.8% vs non-TT, 11.3%; p = 0.33). In multivariate analyses, glycoprotein (GP) IIb/IIIa inhibitor use (hazard ratio [HR], 13.5; 95% confidence interval [CI], 1.7 to 108.3; p = 0.014) and PCI-S of three vessels or left main artery disease (HR, 7.9; 95% CI, 1.6 to 39.2; p = 0.01) were independent predictors for EMB. TT use (HR, 7.1; 95% CI, 1.5 to 32.4; p = 0.012), the occurrence of EMB (HR, 6.7; 95% CI, 1.8 to 25.3; p = 0.005), and baseline anemia (HR, 3.8; 95% CI, 1.2 to 12.5; p = 0.027) were independent predictors for LMB. No differences in major cardiovascular events were observed in patients treated with TT vs non-TT (25.5% vs 21.0%; p = 0.53).. A high rate of major bleeding is observed in AF patients with indication for OAC undergoing PCI-S who receive TT. GP IIb/IIIa inhibitor use and multivessel/left main artery disease during PCI-S were independent predictors for EMB, while TT use, occurrence of EMB, and baseline anemia were independent predictors for LMB.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Stents; Ticlopidine; Warfarin

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Thrombosis; Ticlopidine; Warfarin

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Thrombosis; Ticlopidine; Warfarin

Patients experiencing acute coronary syndromes (ACS) with high-risk features frequently undergo percutaneous coronary intervention (PCI) with stent placement, prompting the requisite administration of aspirin and clopidogrel. The current management of ACS patients with a concomitant indication for warfarin anticoagulant therapy is a question of growing interest and clinical relevance.. We analyzed discharge antithrombotic medication use among all patients with non-ST-segment elevation (NSTE) ACS enrolled in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines (CRUSADE) initiative who were receiving warfarin at the time of hospital admission. Multivariable logistic regression was used to determine factors associated with a decision to discontinue warfarin at discharge.. Among 5673 patients with ACS previously on home warfarin, 1357 (24%) were not discharged on warfarin. In the subset of 1247 patients who underwent coronary stenting, 60% were prescribed triple anticoagulation therapy (aspirin, clopidogrel, and warfarin), 31% were given aspirin and clopidogrel without warfarin, and 3% received warfarin and aspirin without clopidogrel. Factors associated with a decision not to continue warfarin at the time of hospital discharge included in-hospital red blood cell transfusion, non-white race, prior stroke, and discharge clopidogrel use. The decision to continue warfarin at discharge correlated with perceived bleeding risk and was unaffected by patients' stroke risk.. Physician practices vary with regard to the perceived optimal antithrombotic strategy at time of hospital discharge among patients with ACS with a concomitant indication for warfarin. Decisions are influenced primarily by other medication use and anticipated bleeding risk. Further research is needed to guide patient care based on the safety and efficacy of antiplatelet-anticoagulant combined pharmacotherapy.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Ambulatory Care; Angioplasty, Balloon, Coronary; Anticoagulants; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Patient Discharge; Platelet Aggregation Inhibitors; Professional Practice; Registries; Thrombosis; Warfarin

To examine treatment patterns and outcomes of patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) receiving long-term warfarin anticoagulation.. We examined acute medication and invasive cardiac procedure use and in-hospital outcomes among 101,078 patients with NSTE ACS included in the CRUSADE registry. On admission, 7201 patients (7%) were on home warfarin therapy. Compared with non-anticoagulated patients, these patients were older and had more comorbidities, but were less likely to receive acute antiplatelet and antithrombin medications. Patients on warfarin were also less likely to undergo coronary angiography (adjusted OR 0.77, 95% CI 0.70-0.86) and percutaneous coronary intervention (adjusted OR 0.80, 95% CI 0.75-0.86), and had longer waiting times for these procedures when performed. Although patients on warfarin had higher rates of death and major bleeding compared with non-anticoagulated patients, these differences were no longer significant after multivariable adjustment [ORs 0.90 (95% CI 0.80-1.02) and 1.02 (95% CI 0.93-1.11)]. Among patients on warfarin, however, early use of antiplatelet medications was associated with increased transfusion risk.. Despite higher-risk characteristics, warfarin-anticoagulated patients are often more conservatively managed, as early use of antithrombotic therapies may be associated with increased bleeding. Further investigation is needed to determine the optimal choice of therapies for this population.

Topics: Acute Coronary Syndrome; Age Distribution; Aged; Anticoagulants; Disease Progression; Evidence-Based Medicine; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Myocardial Revascularization; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Treatment Outcome; Warfarin

To identify factors associated with the use of single or dual antiplatelet therapy in patients prescribed warfarin following coronary stenting and to investigate whether single (aspirin or thienopyridine) vs. dual antiplatelet therapy plus warfarin leads to an excess of adverse outcomes.. We analysed data from 800 patients with an acute coronary syndrome who underwent coronary stenting (130 patients received a drug-eluting stent) and were discharged on warfarin and either dual (n = 580) or single (n = 220) antiplatelet therapy. The use of single antiplatelet therapy was more common in Europe than in the USA (34 vs. 17%, P < 0.001). There was no difference in major bleeding in hospital or in 6-month mortality or myocardial infarction. In the single antiplatelet group, the use of either aspirin or thienopyridine (clopidogrel or ticlopidine) in combination with warfarin resulted in similar outcomes.. Use of single vs. dual antiplatelet therapy and warfarin following stenting is common. In this observational study, there was no difference in mortality or myocardial infarction at 6 months; however, larger trials are needed to assert any firm recommendations.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Aspirin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Regression Analysis; Risk Assessment; Risk Factors; Stents; Survival Analysis; Treatment Outcome; Warfarin

Contemporary treatment of acute coronary syndrome is based on the combination of acetylsalicylic acid (ASA) and clopidogrel. However, an increasing proportion of patients with cardiovascular disease also have an indication for anticoagulant therapy with warfarin. The combination of ASA, clopidogrel and warfarin, also called the cardiac triple therapy (CTT), is emerging in clinical practice, although little is known about its safety.. To determine the risk of major and minor bleeding associated with the CTT compared with two other regimens using the combination of either ASA and clopidogrel or ASA and warfarin in patients with cardiovascular disease.. A retrospective study was performed of all susceptible patients who may have received the CTT on discharge from the Quebec Heart Institute (Sainte-Foy, Quebec) between 2002 and 2005. The charts of patients treated with the CTT, ASA and clopidogrel, or ASA and warfarin were reviewed and patients were interviewed to document any bleeding episodes.. A total of 183 patients were studied. Overall bleeding in the CTT group was 3% compared with 5% in the group receiving ASA and clopidogrel and 16% in the group receiving ASA and warfarin (P=0.03). Patients who experienced bleeding were older, had more hypertension and had been exposed to their drug regimens for a longer duration. There was no significant difference in major bleeding episodes.. The CCT appears to be relatively safe compared with other regimens. Higher bleeding rates within the ASA-warfarin group emphasize the need to carefully educate and follow patients on combination therapy.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Aspirin; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Quebec; Retrospective Studies; Risk Factors; Ticlopidine; Warfarin