Bleeding with direct oral anticoagulants vs warfarin: clinical experience.

The risk of bleeding in the setting of anticoagulant therapy continues to be re-evaluated following the introduction of a new generation of direct oral anticoagulants (DOACs). Interruption of DOAC therapy and supportive care may be sufficient for the management of patients who present with mild or moderate bleeding, but in those with life-threatening bleeding, a specific reversal agent is desirable. We review the phase 3 clinical studies of dabigatran, rivaroxaban, apixaban, and edoxaban in patients with nonvalvular atrial fibrillation, in the context of bleeding risk and management

Clinical update on the therapeutic use of clopidogrel: treatment of acute ST-segment elevation myocardial infarction (STEMI)

The pathogenesis of ST-elevation myocardial infarction (STEMI) involves plaque disruption, platelet aggregation and intracoronary artery thrombus formation. Aspirin is the cornerstone of antiplatelet therapy in patients with STEMI, reducing the risk of recurrent myocardial infarction or death during the acute phase and long term by about one-quarter. Recent large randomized trials have demonstrated that the addition of clopidogrel to aspirin reduces the risk of major ischemic events by up to a further one-third in patients with STEMI treated with fibrinolytic therapy and undergoing percutaneous coronary intervention, with no significant increase in bleeding. Thus, dual antiplatelet therapy with the combination of clopidogrel and aspirin is becoming the new standard of care for the management of patients with STEMI

How can the results of the COMPASS trial benefit patients with coronary or peripheral artery disease in Poland

Aspirin decreases the risk of recurrent thrombotic events in patients with coronary artery disease or peripheral artery disease but the risk of recurrent events remains high. Long‑term dual antiplatelet therapy or the combination of aspirin and warfarin further reduces the risk of recurrent events, but at the cost of increased bleeding, and neither of these treatments reduce mortality. The COMPASS (Cardiovascular Outcomes in People Using Anticoagulation Strategies) randomized controlled trial involving 27 395 patients from 602 sites in 33 countries (Poland: 9 sites, 518 patients) tested whether low‑dose anticoagulant therapy with the coagulation factor Xa inhibitor rivaroxaban given alone or combined with aspirin reduced thrombotic risk compared with aspirin in patients with apparently stable chronic coronary and/or peripheral artery disease. In patients treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily, compared with aspirin alone, the primary outcome of the composite of cardiovascular death, stroke, or myocardial infarction was decreased by 24% (hazard ratio, 0.76; 95% confidence interval, 0.66 to 0.86; P < 0.001), and mortality by 18% at the cost of a 70% increase in major bleeding but no significant increase in fatal or intracranial bleeding. Results were consistent in patients with coronary artery disease or peripheral artery disease, and the greatest absolute benefit was evident in the highest risk patients, including those with polyvascular disease, mild or moderate heart failure, chronic kidney disease, or diabetes. These results establish the combination of low‑dose rivaroxaban and aspirin as a highly effective treatment to decrease morbidity and mortality rates in patients with atherosclerotic vascular disease.

The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial

10.1186/1471-2318-13-88BMC Geriatrics131

Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease

ObjectivesThe objective of this study was to determine whether colchicine 0.5 mg/day can reduce the risk of cardiovascular events in patients with clinically stable coronary disease.BackgroundThe presence of activated neutrophils in culprit atherosclerotic plaques of patients with unstable coronary disease raises the possibility that inhibition of neutrophil function with colchicine may reduce the risk of plaque instability and thereby improve clinical outcomes in patients with stable coronary disease.MethodsIn a clinical trial with a prospective, randomized, observer-blinded endpoint design, 532 patients with stable coronary disease receiving aspirin and/or clopidogrel (93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and followed for a median of 3 years. The primary outcome was the composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke. The primary analysis was by intention-to-treat.ResultsThe primary outcome occurred in 15 of 282 patients (5.3%) who received colchicine and 40 of 250 patients (16.0%) assigned no colchicine (hazard ratio: 0.33; 95% confidence interval [CI] 0.18 to 0.59; p < 0.001; number needed to treat: 11). In a pre-specified secondary on-treatment analysis that excluded 32 patients (11%) assigned to colchicine who withdrew within 30 days due to intestinal intolerance and a further 7 patients (2%) who did not start treatment, the primary outcome occurred in 4.5% versus 16.0% (hazard ratio: 0.29; 95% CI: 0.15 to 0.56; p < 0.001).ConclusionsColchicine 0.5 mg/day administered in addition to statins and other standard secondary prevention therapies appeared effective for the prevention of cardiovascular events in patients with stable coronary disease

Dual and triple antithrombotic therapies: current patterns of practice and controversies

Dual antiplatelet therapy (DAPT) has been the cornerstone of antithrombotic management for patients undergoing percu­taneous coronary intervention (PCI). Despite low-quality evidence, triple antithrombotic therapy involving acetylsalicylic acid, clopidogrel, and warfarin or non-vitamin K antagonist oral anticoagulant (NOAC) has been recommended in patients with concomitant atrial fibrillation undergoing PCI, who require long-term oral anticoagulation, although such a strategy is associated with a substantially increased risk of bleeding compared with DAPT. NOAC combined with P2Y12 inhibitor alone appears to be safer and as effective as triple therapy with warfarin in patients with acute coronary syndromes based on the results of recent randomised trials on dabigatran and rivaroxaban. The present review summarises the current data on various combinations of antithrombotic agents in terms of their efficacy and safety

Low-dose aspirin for preventing recurrent venous thromboembolism

Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism. Methods We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism. Results During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P = 0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P = 0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P = 0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P = 0.22) or serious adverse events. Conclusions In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. (Funded by National Health and Medical Research Council [Australia] and others; Australian New Zealand Clinical Trials Registry number, ACTRN12605000004662.)Health Research Council (New Zealand), Australasian Society of Thrombosis and Hemostasis, National Heart Foundation of Australia, Bayer HealthCare, National Health and Medical Research Council (Australia) program grant 103778

Balancing the Benefits and Risks of 2 Doses of Dabigatran Compared With Warfarin in Atrial Fibrillation

ObjectivesThis study sought to compare the net clinical benefit of dabigatran 110 mg bid and 150 mg bid with that of warfarin in patients with atrial fibrillation (AF).BackgroundIn patients with AF, dabigatran 110 mg bid and 150 mg bid are associated with similar rates of death. However, the higher dose reduces ischemic stroke and increases bleeding compared with the lower dose. Therefore, there is uncertainty about how to evaluate the overall benefit of the 2 doses.MethodsIn 18,113 AF patients in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial, we used a previously developed method for integrating ischemic and bleeding events as “ischemic stroke equivalents” in order to compare a weighted benefit of 2 doses of dabigatran with each other, and with that of warfarin.ResultsCompared with warfarin, there was a significant decrease in ischemic stroke equivalents with both dabigatran doses: –0.92 per 100 patient years (95% confidence interval [CI]: –1.74 to −0.21, p = 0.02) with dabigatran 110 mg bid and –1.08 (95% CI: –1.86 to −0.34, p = 0.01) with dabigatran 150 mg bid. There was no significant difference in ischemic stroke equivalents between the 2 doses: –0.16 (95% CI: –0.80 to 0.43) comparing dabigatran 150 mg bid with 110 bid. When including death in the weighted benefit calculations, the results were similar.ConclusionsOn a group level both doses of dabigatran as compared with warfarin have similar benefits when considering a weighted estimate including both efficacy and safety. The similar overall benefits of the 2 doses of dabigatran versus warfarin support individualizing the dose based on patient characteristics and physician and patient preferences. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600

Dwukierunkowe hamowanie w miażdżycy układu sercowo-naczyniowego — ostatnie postępy

Choroba układu sercowo-naczyniowego o podłożu miażdżycy (ASCVD, atherosclerotic cardiovascular disease), która obejmuje chorobę wieńcową (CAD, coronary artery disease), chorobę naczyń mózgowych oraz chorobę tętnic obwodowych (PAD, peripheral arterial disease), wiąże się z dużą zachorowalnością, śmiertelnością i kosztami opieki zdrowotnej. Terapia przeciwpłytkowa była od dawna podstawą leczenia przeciwzakrzepowego w profilaktyce pierwszych i ponownych incydentów ASCVD. Jednak ostatnie randomizowane badania pokazały zalety i efektywność kosztową strategii dwukierunkowego hamowania (DPI, dual pathway inhibition) w ostrej i przewlekłej ASCVD. Kwas acetylosalicylowy stosowany w skojarzeniu z małą dawką rywaroksabanu działają synergistycznie, hamując aktywację płytek krwi i generację trombiny, tym samym zapobiegając powstawaniu skrzepliny. Wśród pacjentów z niedawnym ostrym zespołem wieńcowym (ACS, acute coronary syndrome), ci z dodatnimi biomarkerami sercowymi, zawałem serca z uniesieniem odcinka ST lub historią niewydolności serca odnoszą największe bezwzględne korzyści. Wśród pacjentów z przewlekłą ASCVD, ci z zajęciem dwóch lub więcej łożysk naczyniowych, niewydolnością serca, przewlekłą chorobą nerek lub cukrzycą odnoszą największe bezwzględne korzyści. Dodatkowe badania są w trakcie realizacji, celem oceny wpływu terapii DPI w innych interesujących populacjach, w tym pacjentów z ACS z dużym ryzykiem powstania skrzepliny w lewej komorze, wewnątrzczaszkową miażdżycą tętnic po niedawno przebytym przemijającym napadzie niedokrwienia mózgu lub udarze, chorobą tętnic obwodowych z chromaniem przestankowym lub po rewaskularyzacji kończyn dolnych i zaawansowaną przewlekłą chorobą nerek z ASCVD lub czynnikami ryzyka ASCVD. Dalsze badania są potrzebne w celu oceny możliwych dodatkowych korzyści z łączenia rywaroksabanu z klopidogrelem lub tikagrelorem zamiast kwasu acetylosalicylowego

Dual pathway inhibition for atherosclerotic cardiovascular disease: Recent advances

Atherosclerotic cardiovascular disease (ASCVD), which includes coronary artery disease (CAD), cerebrovascular disease, and peripheral arterial disease (PAD) is associated with significant morbidity, mortality, and healthcare costs. Antiplatelet therapy has long been the mainstay of antithrombotic therapy for the prevention of first-ever and recurrent ASCVD events. More recently, however, randomized trials have demonstrated the benefits and cost-effectiveness of a dual pathway inhibition (DPI) strategy in acute and chronic ASCVD. When used in combination, aspirin and low-dose rivaroxaban work synergistically to inhibit platelet activation and thrombin generation, thereby preventing thrombus formation. Among patients with recent acute coronary syndrome (ACS), those with positive cardiac biomarkers or ST-segment elevation myocardial infarction, or a history of heart failure derive the greatest absolute benefits. Among patients with chronic ASCVD, those with involvement of two or more vascular beds, heart failure, chronic kidney disease, or diabetes derive the greatest absolute benefits. Additional trials are underway to assess the impact of DPI therapy in other populations of interest, including patients with ACS at high risk of left ventricular thrombus formation, intracranial atherosclerotic disease with recent transient ischemic attack or stroke, peripheral arterial disease with limiting claudication or post lower extremity revascularization, and advanced chronic kidney disease with ASCVD or risk factors for ASCVD. Further work is required to assess the possible added benefit of combining rivaroxaban with clopidogrel or ticagrelor instead of aspirin