Risks Of Antithrombotic Therapy Research Articles

Highlights from the 2019 International Aspirin Foundation Scientific Conference, Rome, 28 June 2019: benefits and risks of antithrombotic therapy for cardiovascular disease prevention

Highlights from the 2019 International Aspirin Foundation Scientific Conference, Rome, 28 June 2019: benefits and risks of antithrombotic therapy for cardiovascular disease prevention

Clinical benefits and risks of antithrombotic therapy in patients with atrial fibrillation with comorbidities – A report from the CHART-2 Study

BackgroundThe benefits of antithrombotic therapy (ATT) for atrial fibrillation (AF) are occasionally offset by major bleeding complications. However, the clinical benefits and risks of ATT in AF patients, with special references to comorbidities, such as heart failure (HF), coronary artery disease (CAD), and the patterns of AF, remain to be fully elucidated. MethodsA total of 3221 consecutive AF patients from our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N = 10,219) were divided into 4 groups based on ATT at enrollment; no-ATT, anticoagulant alone, antiplatelet alone, and both of them (AC&AP). Then, efficacy and safety outcomes including thromboembolic events, major bleeding, and mortality were evaluated among the 4 groups. ResultsAnticoagulant monotherapy was associated with reduced risk of ischemic stroke in patients with but not in those without HF, CAD, or non-paroxysmal AF. Although there was no significant difference in major bleeding among the 4 groups, a composite of thromboembolism and major bleeding occurred more frequently in the AC&AP group, even in combination with anticoagulants and single antiplatelet therapy, indicating that the combination therapy is more harmful than anticoagulant monotherapy for AF patients, especially for those with HF or CAD. Lastly, no-ATT group was associated with worse prognosis compared with other 3 groups. ConclusionsThese results indicate that ATT is beneficial for AF patients particularly for those with HF, CAD, or non-paroxysmal AF and that among ATT, anticoagulant monotherapy may be most profitable for both clinical benefits and risks for AF patients.

Abstract WP528: Safety and Effectiveness of Rivaroxaban Among Japanese Elderly Patients With Nonvalvular Atrial Fibrillation in Everyday Clinical Practice

Introduction: Nonvalvular atrial fibrillation (AF) is common in elderly patients, who face increased risk of thromboembolism and bleeding during antithrombotic therapy. Xarelto post-authorization safety & effectiveness study in Japanese patients with atrial fibrillation (XAPASS) is a prospective observational post-marketing surveillance study mandated by the Japanese authority. It aims to examine safety and effectiveness of rivaroxaban in everyday clinical practice. This analysis evaluated one-year outcomes and patient characteristics associated with major bleeding or thromboembolic events among elderly patients enrolled in XAPASS. Methods: A total of 11,308 patients with AF newly starting rivaroxaban were enrolled between April 2012 and June 2014. As of September 2017, one year follow-up data were collected from 9578 patients, and 4685 patients (48.9%) were aged ≥75 years. Results: Patients aged ≥75 years had higher rates of major bleeding (2.22 versus 1.35 events per 100 patient-years; p=0.004), and the composite endpoint of stroke, systemic embolism or myocardial infarction (2.41 versus 1.21 events per 100 patient-years; p<0.0001) compared with those aged <75 years. Rates of intracranial hemorrhage were less than 1% in both patient groups aged ≥75 years and <75 years (0.85 versus 0.59 events per 100 patient-years). There was no significant difference in major bleeding or thromboembolism among patients in age groups of 75-79, 80-84, and ≥85 years. Multivariate analysis identified hepatic impairment and concomitant use of acetylsalicylic acid as risk factors of major bleeding events in patients aged ≥75 years (p=0.041 and p<0.0001, respectively). History of stroke was identified as a risk factor of thromboembolic events in the same patient group (p<0.0001). Conclusions: Although elderly patients had higher rates of bleeding and thromboembolic events than younger patients, no significant difference was found in the outcomes between age groups of 75-79, 80-84, and ≥85 years. Benefit and risk of antithrombotic therapy should be thoroughly assessed in elderly patients. Additionally, elderly patients with risk factors of bleeding or thromboembolic events should be carefully monitored while taking anticoagulants.

Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review.

Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage. To evaluate the risks and benefits of antithrombotic therapy in adults with ET. Multiple databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, through 4 March 2017. Randomized and observational studies of antiplatelet or anticoagulant therapy, published in any language and reporting thrombotic or hemorrhagic events. Two reviewers independently extracted data, assessed risk of bias, and graded certainty of evidence. No relevant randomized trials were identified. Twenty-four observational studies (18 comparative and 6 single-group) involving 6153 patients followed for 31711 patient-years were reviewed; most were deemed to have high risk of bias. Most patients receiving antiplatelet therapy (3613 of 4527 [80%]) received low-dose aspirin (50 to 150 mg/d); 914 (20%) received high-dose aspirin (300 to 600 mg/d), dipyridamole, or other agents. Overall, findings were inconsistent and imprecise. The reported incidence rates of thrombosis, any bleeding, and major bleeding without antiplatelet therapy ranged from 5 to 110 (median, 20), from 3 to 39 (median, 8), and from 2 to 53 (median, 6) cases per 1000 patient-years, respectively. The reported relative risks for thrombosis, any bleeding, and major bleeding with antiplatelet therapy compared with none ranged from 0.26 to 3.48 (median, 0.74), from 0.48 to 11.04 (median, 1.95), and from 0.48 to 5.17 (median, 1.30), respectively. Certainty of evidence was rated low or very low for all outcomes. No randomized trials, no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes. Available evidence about the risk-benefit ratio of antiplatelet therapy in adults with ET is highly uncertain. Regional Medical Associates. (PROSPERO: CRD42015027051).

A review of sex-specific benefits and risks of antithrombotic therapy in acute coronary syndrome.

Over the past decade, more men than women have shown improved outcomes from antithrombotic therapies after acute coronary syndrome (ACS), which raises the question of whether there are sex-specific differences in treatment patterns and response to therapy. Differences in presenting clinical characteristics, pathophysiologic profile, and disparities in treatment may contribute to this outcomes discrepancy. Analyses of large trials and registry data suggest that male and female ACS patients experience similar benefits from antithrombotic therapy without significant difference in treatment utilization rates, yet women are consistently at higher risk of bleeding than men. Bleeding may result in antithrombotic treatment disruption, which increases the risk of long-term thrombotic events. Additionally, female ACS patients are more likely to receive suboptimal medication dosing and have lower rates of long-term medication adherence. These differences have significant clinical implications for women, indicating the need for strategies that will optimize initial treatment and long-term management attuned to these recognized sex-specific gaps.

Um estudo de qualidade numa unidade de saúde familiar para a melhoria da qualidade da terapêutica profilática antitrombótica prescrita a doentes com fibrilhação auricular

IntroductionAtrial fibrillation is the most common cardiac arrhythmia and has important clinical repercussions, increasing thromboembolic events and mortality. The CHA2DS2-VASc and HAS-BLED scores assist the clinician in assessing the benefits and risks of antithrombotic therapy. ObjectiveThe aim of this study was to assess and improve the quality of prophylactic antithrombotic therapy prescribed to patients with atrial fibrillation. MethodsThis was a quality study, based on a cycle of assessment and improvement, applied to the population of a family health unit, consisting of an initial assessment, an educational intervention and a second assessment. Both scores were calculated for all patients. Whenever the CHA2DS2-VASc score recommended initiation of anticoagulation, the risk was calculated by the HAS-BLED score; it was thus possible to determine for each patient if the prescribed therapy was appropriate. ResultsThe first assessment included 105 patients, of whom 49.5% had appropriate prophylactic therapy according to their scores. In the second assessment, four months after the educational intervention, 60.0% had been prescribed appropriate therapy, which represented a 21.2% improvement. ConclusionsIn both assessments, inappropriate treatment was due to non-prescription of prophylactic oral anticoagulation. This quality cycle serves as a tool for continuous assessment in the pursuit of improved care for patients with atrial fibrillation.

A quality study to improve prophylactic antithrombotic therapy prescribed to patients with atrial fibrillation

IntroductionAtrial fibrillation is the most common cardiac arrhythmia and has important clinical repercussions, increasing thromboembolic events and mortality. The CHA2DS2‐VASc and HAS‐BLED scores assist the clinician in assessing the benefits and risks of antithrombotic therapy. ObjectiveThe aim of this study was to assess and improve the quality of prophylactic antithrombotic therapy prescribed to patients with atrial fibrillation. MethodsThis was a quality study, based on a cycle of assessment and improvement, applied to the population of a family health unit, consisting of an initial assessment, an educational intervention and a second assessment. Both scores were calculated for all patients. Whenever the CHA2DS2‐VASc score recommended initiation of anticoagulation, the risk was calculated by the HAS‐BLED score; it was thus possible to determine for each patient if the prescribed therapy was appropriate. ResultsThe first assessment included 105 patients, of whom 49.5% had appropriate prophylactic therapy according to their scores. In the second assessment, four months after the educational intervention, 60.0% had been prescribed appropriate therapy, which represented a 21.2% improvement. ConclusionsIn both assessments, inappropriate treatment was due to non‐prescription of prophylactic oral anticoagulation. This quality cycle serves as a tool for continuous assessment in the pursuit of improved care for patients with atrial fibrillation.

Combined blockade of thrombin anion binding exosite-1 and PAR4 produces synergistic antiplatelet effect in human platelets

Thrombin exosite-1 mediates the specific binding of thrombin with fibrinogen and protease-activated receptor (PAR) 1. Exosite-1 inhibitors have been shown to effectively decrease the clotting activity of thrombin, while their antiplatelet effects are relatively weak. In the present study, the inhibitory effects of two exosite-1 inhibitors, hirugen and HD1, but not the exosite-2 inhibitor HD22, on thrombin-induced platelet aggregation and P-selectin expression were dramatically enhanced by a PAR4 antagonist, YD-3. In contrast, the PAR1 antagonist SCH-79797 did not affect the antiplatelet effects of exosite-1 inhibitors. The exosite-1 inhibitors and YD-3 prevented the Ca2+ spike and the prolonged Ca2+ response in thrombin-stimulated platelets, respectively; and combination of these two classes of agents led to abolishment of Ca2+ signal. Unlike exosite-1 inhibitors, the antiplatelet effects of the active site inhibitor PPACK and the bivalent inhibitor bivalirudin were not significantly enhanced by YD-3. In addition, the platelet-stimulating activity of γ-thrombin, an autolytic product of α-thrombin which lacks exosite-1, was inhibited by YD-3. These results suggest that the synergistic antiplatelet effects of exosite-1 inhibitor and PAR4 antagonist are resulted from combined blockade of PAR1 and PAR4 in platelets. In fibrinogen or plasma clotting assay, YD-3 neither prolonged the clotting time on its own nor enhanced the anticoagulant activity of exosite-1 inhibitors. Therefore, the combined blockade of exosite-1 and PAR4 may offer a potential strategy for improving the balance of benefits and risks of antithrombotic therapy.

Clinical usefulness in geriatric patients of combining CHADS2 and HEMORR2HAGES scores to guide antithrombotic prophylaxis in atrial fibrillation

Two scores exist to assess the benefits and risks of antithrombotic therapy in patients with atrial fibrillation: CHADS2 [for Congestive heart failure, Hypertension, Age over 75, Diabetes mellitus; and 2 points for a history of Stroke] and HEMORR2HAGES [for Hepatic or renal failure, Ethanol abuse, Malignancy, Older (age over 75), Reduced platelet count or function, 2 points for Rebleeding risk Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk (including neurodegenerative and psychiatric disorders) and history of Stroke]. The potential value of using both scores routinely was studied in order to guide the choice of antithrombotic therapy for geriatric patients. Retrospective calculation of CHADS2 and HEMORR2HAGES scores and discharge treatment were collected for all patients with atrial fibrillation during a six-month period. All files were analysed when there were differences between therapeutic choices and the results of analysis of combining the two scores. 83 patients were identified. Their mean age was 89.2±4.9 years and 30% of them were on oral anticoagulants on discharge. Usual prescription habits of oral anticoagulants correlated strongly with each of the scores and with the difference between the two scores. The clinical usefulness of using the two scores seemed poor since they indicated that two-thirds of the patients had a similar risk of hemorrhagic and ischemic events. Based on this preliminary study, the CHADS2 and HEMORR2HAGES scores are associated with the prescription of oral anticoagulants, but their routine use may not significantly change the choice of antithrombotic therapy for patients with atrial fibrillation.

Antithrombotic therapy for congestive heart failure

Patients with congestive heart failure (CHF) are at increased risk of thromboembolic events. However, there is much debate and uncertainty over the use of antithrombotic therapy in these patients. The evidence for oral anticoagulation is limited, although large randomised trial data are forthcoming. Aspirin may be detrimental for heart failure due to a possible interaction with angiotensin-converting enzyme inhibitors, leading to increased hospitalisations from decompensated heart failure. The objective of this review article is to summarise the available evidence regarding the risk of stroke and thromboembolic events in CHF patients, as well as the effectiveness and risks of antithrombotic therapy in these patients.

Thrombosis in Clinical Practice. Edited by: Andrew D Blann, Gregory YH Lip, Alexander GG Turpie.

As mentioned by editors, expectant readers of Thrombosis in Clinical Practice are physicians, general practitioners, nurse practitioners, and healthcare workers. With this in mind I browsed Thrombosis in Clinical Practice. Thrombosis is a fast moving area and is not easy to give updated information of its pathophysiology and treatment in about 300 pages as it was successfully done in this book. This multiauthored text combines basic concepts of mechanisms of thrombosis formation as well as therapeutic approaches. It provides short overviews on risk factors, therapeutics and a systematic discussion of arterial and venous thrombosis management with final recommendations according to authors experience. It successfully delivers concise information on all aspects of a given type of thrombosis for physicians and nurses who care for patients with thrombosis related diseases. The first five chapters review mechanism of thrombus formation (although importance of inflammation was omitted in Chapter 1), role of hemostatic system in arterial and venous thrombosis, characteristics of what authors call commonly used anticoagulant and antiplatelet (which include aspirin, heparin, and warfarin starting with an interesting historical perspective of each of them). Without doubt risk of bleeding is most critical aspect of patients under antithrombotic treatment; it happens and what to do are questions answered in Chapter 4. Factors which determine thrombophilia are discussed in Chapter 5. Practical recommendations for screening patients with potential or already developed thrombotic process are noteworthy. The following Chapters 6 to 12 deal with treatment of arterial and venous thrombosis and include management of atrial fibrillation where known, well established therapies are discussed. In cardiac valves, Chapter 7, a comprehensive indication for used of oral anticoagulant with or without aspirin and management of pregnant patients was explained. Since some not so recent data have been included in beginning of this chapter authors missed to mention that in patients with cardiac valves prostheses, first combined therapy (oral anticoagulant plus dipyridamole) for thrombotic preventing treatment was published by Sullivan et al. (N Engl J Med. 1971;284:1391-4), and belongs to our group first report on use of aspirin plus oral anticoagulant (Altman et al. J.Thorac.Cardiov. Surg. 72: 127,1976). Chapters 8 to 11 review benefit and risk of antithrombotic therapy in coronary artery disease, thrombosis prevention after coronary interventions and, an updated discussion on risk factors, pathophysiology, diagnosis and antithrombotic therapy in peripheral arterial disease and ischemic stroke. Chapter 12 deals with an important and still controversial topic: Management of venous thromboembolism during pregnancy. The authors discuss conflictive positions in diagnostic as well as in treatment of deep venous thrombosis in pregnant women. The antithrombotic treatment in women with recurrent miscarriage and thrombophilia which is conflictive and still unresolved is not discussed in this chapter. Chapter 13 was dedicated to thrombophilia. I wonder why it was included at end of book and not among first 5 Chapters. I also wonder why Ian Jennings omits to discuss whether decrease of fibrinolysis is (or not) a potential thrombotic risk factor. Importantly, a chapter on thrombosis in children was incorporated in this book and finally, a chapter on new drugs for anticoagulant therapy, which could be called the after coumadin/heparin era, was also included with updated information on pentasacharides fondaparinux and idraparinux, on drugs affecting factor VII activity, direct Factor Xa and direct thrombin inhibitors. Therapeutic characteristics of antiplatelet drugs is provide in this Chapter. This part of article shows feeble beneficial effect of clopidogrel plus aspirin, in reducing combining risk of ischemic stroke, MI or vascular death compared with aspirin in several artery diseases and likely to be beneficial in patients underwent percutaneous coronary intervention. The antithrombotic capacity of glicoprotein IIb-IIIa (integrin α2b/β3) inhibitors, potential value of von Willebrand factor antibody AJW 200 and thrombolytic therapy are also discussed. This textbook is particularly interesting for general practitioners, medical students and trainees in haematology. It will be useful for physicians in several disciplines. In short: It fulfils its stated purpose.

Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials

Atrial fibrillation is associated with an increased risk of ischemic stroke. Data on individual patients were pooled from five recently completed randomized trials comparing warfarin (all studies) or aspirin (the Atrial Fibrillation, Aspirin, Anticoagulation Study and the Stroke Prevention in Atrial Fibrillation Study) with control in patients with atrial fibrillation. The purpose of the analysis was to (1) identify patient features predictive of a high or low risk of stroke, (2) assess the efficacy of antithrombotic therapy in major patient subgroups (eg, women), and (3) obtain the most precise estimate of the efficacy and risks of antithrombotic therapy in atrial fibrillation. For the warfarin-control comparison there were 1889 patient-years receiving warfarin and 1802 in the control group. For the aspirin-placebo comparison there were 1132 patient-years receiving aspirin and 1133 receiving placebo. The daily dose of aspirin was 75 mg in the Atrial Fibrillation, Aspirin, Anticoagulation Study and 325 mg in the Stroke Prevention in Atrial Fibrillation Study. To monitor warfarin dosage, three studies used prothrombin time ratios and two used international normalized ratios. The lowest target intensity was a prothrombin time ratio of 1.2 to 1.5 and the highest target intensity was an international normalized ratio of 2.8 to 4.2. The primary end points were ischemic stroke and major hemorrhage, as assessed by each study. At the time of randomization the mean age was 69 years and the mean blood pressure was 142/82 mm Hg. Forty-six percent of the patients had a history of hypertension, 6% had a previous transient ischemic attack or stroke, and 14% had diabetes. Risk factors that predicted stroke on multivariate analyses in control patients were increasing age, history of hypertension, previous transient ischemic attack or stroke, and diabetes. Patients younger than 65 years who had none of the other predictive factors (15% of all patients) had an annual rate of stroke of 1.0%, 95% confidence interval (CI) 0.3% to 3.0%. The annual rate of stroke was 4.5% for the control group and 1.4% for the warfarin group (risk reduction, 68%; 95% CI, 50% to 79%). The efficacy of warfarin was consistent across all studies and subgroups of patients. In women, warfarin decreased the risk of stroke by 84% (95% CI, 55% to 95%) compared with 60% (95% CI, 35% to 76%) in men. The efficacy of aspirin was not as consistent. The risk reduction with 75 mg of aspirin in the Atrial Fibrillation, Aspirin, Anticoagulation Study was 18% (95% CI, 60% to 58%), and with 325 mg of aspirin in the Stroke Prevention in Atrial Fibrillation Study the risk reduction was 44% (95% CI, 7% to 66%). When both studies were combined the risk reduction was 36% (95% CI, 4% to 57%). The annual rate of major hemorrhage (intracranial bleeding or a bleed requiring hospitalization or 2 units of blood) was 1.0% for the control group, 1.0% for the aspirin group, and 1.3% for the warfarin group. In these five randomized trials warfarin consistently decreased the risk of stroke in patients with atrial fibrillation (a 68% reduction in risk) with virtually no increase in the frequency of major bleeding. Patients with atrial fibrillation younger than 65 years without a history of hypertension, previous stroke or transient ischemic attack, or diabetes were at very low risk of stroke even when not treated. The efficacy of aspirin was less consistent. Further studies are needed to clarify the role of aspirin in atrial fibrillation.