Contemporary Clinical Use of Aspirin: Mechanisms of Action, Current Concepts, Unresolved Questions, and Future Perspectives

2021 ◽  
Author(s):  
Mikael Christiansen ◽  
Erik Lerkevang Grove ◽  
Anne-Mette Hvas
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Clinical Use ◽  
Action Current ◽  
Potential Clinical Benefit ◽  
Treatment Indications ◽  
Prevention Of Cardiovascular Disease

AbstractThe ability of aspirin to inhibit platelet aggregation has positioned this agent within the most frequently used drugs worldwide. The aim of this article is to review the contemporary clinical use of aspirin and also to discuss unresolved issues not yet translated into clinical practice. Results from several clinical trials have led to strong guideline recommendations for aspirin use in the acute management and secondary prevention of cardiovascular disease. On the contrary, guidelines regarding aspirin use as primary prevention of cardiovascular disease are almost conservative, supported by recent trials reporting that the bleeding risk outweighs the potential benefits in most patients. In pregnancy, aspirin has proved efficient in preventing preeclampsia and small-for-gestational-age births in women at high risk, and is hence widely recommended in clinical guidelines. Despite the vast amount of clinical data on aspirin, several unresolved questions remain. Randomized trials have reported that aspirin reduces the risk of recurrent venous thromboembolism, but the clinical relevance remains limited, because direct oral anticoagulants are more effective. Laboratory studies suggest that a twice-daily dosing regimen or evening intake may lead to more efficient platelet inhibition, and the potential clinical benefit of such strategies is currently being explored in ongoing clinical trials. Enteric-coated formulations of aspirin are frequently used, but it remains unclear if they are safer and as efficient as plain aspirin. In the future, aspirin use after percutaneous coronary interventions might not be mandatory in patients who also need anticoagulant therapy, as several trials support shorter aspirin duration strategies. On the other hand, new treatment indications for aspirin will likely arise, as there is growing evidence that aspirin may reduce the risk of colorectal cancer and other types of cancer.

Extended-Duration Use of Direct Oral Anticoagulants to Prevent VTE in Acutely III Medical Patients

2019 ◽  
Vol 34 (2) ◽  
pp. 99-108
Author(s):  
Jessica W. Skelley ◽  
Angela R. Thomason ◽  
Lauren N. Hammond
Keyword(s):  
Clinical Trials ◽  
Human Subjects ◽  
Data Extraction ◽  
Oral Anticoagulants ◽  
Adult Population ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Medical Patients ◽  
Bleeding Events ◽  
Extended Duration

OBJECTIVE: To evaluate current clinical evidence for the use of direct oral anticoagulants (DOACs) for extended-duration thromboprophylaxis in the acutely ill medical population for venous thromboembolism (VTE) and bleeding events.<br/> DATA SOURCES: Were obtained through a MEDLINE/PubMed search for clinical trials conducted from March 2008 to 2018 using relevant key words. Limitations of English and human subjects were applied to search results.<br/> STUDY SELECTION AND DATA EXTRACTION: Forty-one articles were identified, and abstracts reviewed by the authors for inclusion of the study population (acutely ill medical patients) and VTE outcomes. Clinical studies evaluating the use of DOACs for extended duration of VTE prevention in acutely ill medical patients were included in the review, resulting in three clinical trials and two subgroup analyses. The participants enrolled had an overall mean age of 71.4 years.<br/> DATA SYNTHESIS: The DOAC trials collectively demonstrated a positive outcome in composite endpoints of VTE prevention with extended-duration thromboprophylaxis in acutely ill medical patients compared with enoxaparin. As for safety, rivaroxaban and apixaban trials reported more major bleeding events compared with enoxaparin. The betrixaban trial demonstrated no difference in bleeding compared with enoxaparin.<br/> CONCLUSION: DOACs reduced the number of VTE events in acutely ill medical patients on extended-duration thromboprophylaxis, but with an overall increased bleeding risk. An individualized patient approach based on risk factors should be utilized for treatment with extended-duration DOAC in the older adult population with recent hospitalization.

scholarly journals Novel bleeding risk score for patients with atrial fibrillation on oral anticoagulants, including direct oral anticoagulants

2021 ◽  
Author(s):  
Luise Adam ◽  
Martin Feller ◽  
Lamprini Syrogiannouli ◽  
Cinzia Del‐Giovane ◽  
Jacques Donzé ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Score ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk

Abstract 17301: Safety of Direct Oral Anticoagulants Compared to Warfarin for Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali Hage ◽  
Daniel Dolan ◽  
Viviane G Nasr ◽  
Luis Castelo-Branco ◽  
Daniel Motta-Calderon ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Cardiac Surgery ◽  
Hospital Readmission ◽  
Lower Risk ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Secondary Outcome ◽  
Systemic Embolization

Introduction: The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation (POAF) is limited and mostly founded on clinical trials that excluded this patient population. Hypothesis: We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with POAF. Methods: We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality, with secondary outcome of hospital readmission. We performed a random-effects meta-analysis. Results: We found 3 clinical trials, 1 prospective and 12 retrospective cohort studies eligible for inclusion with a total of 10,538 patients (3,207 DOAC patients and 7,331 warfarin patients). The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50 to 0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41 to 1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74 to 1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74 to 1.37, I2: 26.5%) The secondary outcome of hospital readmission had similar risk between groups. Conclusions: Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding or mortality.

scholarly journals Bleeding Risk in Non-Valvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3672-3672 ◽  
Author(s):  
Yimin Pearl Wang ◽  
Rohan Kehar ◽  
Alla Iansavitchene ◽  
Alejandro Lazo-Langner
Keyword(s):  
Major Bleeding ◽  
Lower Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Significant Difference

Introduction: The standard oral anticoagulant therapy administered to non-valvular AF patients has typically been Vitamin K Antagonists (VKA) particularly warfarin. In recent years, Direct Oral Anticoagulants (DOACs) including Direct Thrombin Inhibitors (DTI) and Direct Factor Xa inhibitors (FXa inhibitors) have become an alternative to warfarin. Randomized trials comparing warfarin and DOACs showed comparable effectiveness without significant additional major bleeding risk. However, bleeding events in RCTs may differ from those in daily use due to the routine exclusion of patients with a higher risk of bleeding from many studies. We aimed to assess bleeding risk between DOACs and warfarin in AF patients in observational studies and we also sought to determine differences between patients that were experienced or naïve to oral anticoagulants. Methods: A systematic literature search was conducted in the OVID MEDLINE® and EMBASE® electronic databases. Observational studies and randomized control trials (RCT) from 1990 to January 2019 were retrieved and examined by two independent reviewers. A pooled effect hazard ratio (HR) was calculated using a random effects model using the generic inverse variance method. Subgroup analyses according to previous exposure to anticoagulants, study type, funding type and DOAC type were conducted. The primary outcome was major bleeding risk. The secondary outcome was clinically relevant non-major bleeding. All studies must have used an established or validated definition of major bleeding. Results: The initial literature search identified 3359 potentially eligible citations. After primary screening, 150 articles were eligible for full text review and there were 35 studies including 2,356,201 patients that met the inclusion criteria. Overall, patients on DOACs were less likely to experience a bleeding event compared to warfarin (HR 0.78, 95%CI 0.71, 0.85, P&lt;0.001). The results were consistent when analyzing patients receiving DTIs or FXa inhibitors (DTI: HR 0.76, 95% CI 0.67,0.87; FXa inhibitors: HR 0.79, 95% CI 0.69,0.89). However, among patients receiving factor Xa inhibitors, there was a significant difference in the risk of bleeding according to individual drug. Among patients receiving rivaroxaban the risk of bleeding was similar to warfarin (HR 0.98, 95%CI 0.91,1.06, p=0.60) whereas in those receiving apixaban there was a 40% reduction in the risk of bleeding compared to warfarin (HR 0.60, 95%CI 0.50,0.71, p&lt;0.001) (Figure 1). Three studies reported information according to previous anticoagulant exposure. The overall pooled hazard ratio was 0.68 (95% CI 0.55, 0.82 p&lt;0.001) in favor of patients on DOACs. In the subgroup analysis of previous anticoagulant use, the risk of bleeding was lower for DOACs compared to warfarin in both the experienced population (HR 0.70, 95%CI 0.51, 0.96) and the naïve population (HR 0.64, 95% CI 0.47,0.87). However, heterogeneity was moderate to high among both subgroups. Conclusion: This review and meta-analysis of observational studies including over 2.3 million patients showed that overall DOACs have a lower risk of major bleeding and clinically relevant non-major bleeding compared to warfarin. Most importantly, although the pooled effect estimate did not differ between DTIs and FXa inhibitors, among patients receiving FXa inhibitors there was a significant difference between individual agents. Patients on apixaban had a significantly lower risk of bleeding compared to warfarin in contrast to patients on rivaroxaban who had a similar risk. Disclosures No relevant conflicts of interest to declare.

scholarly journals Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: Consensus Recommendations by the Asian Pacific Society of Cardiology on Strategies for Thrombotic and Bleeding Risk Management

2021 ◽  
Vol 16 ◽  
Author(s):  
Daniel TT Chong ◽  
Felicita Andreotti ◽  
Peter Verhamme ◽  
Jamshed J Dalal ◽  
Noppacharn Uaprasert ◽  
...  
Keyword(s):  
Disease Burden ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Asia Pacific ◽  
Asian Populations ◽  
Asian Patients ◽  
Consensus Statements ◽  
Asian Pacific

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations

2021 ◽  
Author(s):  
Paul P. Dobesh ◽  
Molly M. Kernan ◽  
Jenni J. Lueshen
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Safety Data ◽  
Special Populations ◽  
Dose Selection ◽  
Phase 3 ◽  
Optimal Drug

AbstractThere are currently more than 7 million patients taking a direct oral anticoagulant (DOAC), with more new prescriptions per year than warfarin. Despite impressive efficacy and safety data for the treatment of venous thromboembolism, patients with obesity or advanced renal impairment represented a small portion of the patients enrolled in the phase 3 clinical trials. Therefore, to evaluate the potential use of DOACs in these special populations, clinicians need to have an understanding of the pharmacokinetics and pharmacodynamics of these agents in these settings. Since data from randomized controlled trials are limited, data from observational trials are helpful in gaining comfort with the use of DOACs in these special populations. Selecting the appropriate dose for each agent is imperative in achieving optimal patient outcomes. We provide an extensive review of the pharmacokinetics, pharmacodynamics, phase 3 clinical trials, and observational studies on the use of DOACs in patients with advanced renal impairment, obesity, or other weight-related special populations to provide clinicians with a comprehensive understanding of the data for optimal drug and dose selection.

Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alexander C Perino ◽  
Krishna Pundi ◽  
Jun Fan ◽  
Susan K Schmitt ◽  
Mitra Kothari ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Warfarin Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Warfarin Treatment ◽  
Treatment Analysis ◽  
Using Data ◽  
Favorable Safety

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.

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