scholarly journals Antithrombotic Therapy in Myocardial Infarction: Historic Perils and Current Challenges—A 70-Year Journey

2020 ◽  
Vol 120 (10) ◽  
pp. 1352-1356
Author(s):  
Dion Stub ◽  
Himawan Fernando ◽  
James D. McFadyen ◽  
Jathushan Palasubramaniam ◽  
James Shaw ◽  
...  

AbstractThere have been numerous and intriguing advancements in antithrombotic therapy for myocardial infarction since it was described in the earliest issues of Thrombosis and Haemostasis. In this article, we revisit historical breakthroughs and describe the four most challenging contemporary themes relating to antithrombotic therapy in myocardial infarction. In all four, the challenge is to find the best balance of reducing specific levels of ischaemic risks without increasing bleeding risk. The first is the question of the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). This includes discussion of monotherapy after a period of DAPT. The second relates to the role of genotype and phenotype-guided individualisation of antiplatelet therapy. There is emerging evidence for a role of pheno/genotyping in identifying individuals at high risk for recurrent ischaemic events or in guiding the timing of cardiac surgery for patients on DAPT. The third addresses the increasing evidence for dual pathway inhibition, for example, with rivaroxaban in addition to aspirin in patients where high ischaemic and low bleeding risk is demonstrated. Finally the fourth highlights the challenge of the most appropriate combination of antiplatelet and anticoagulation therapy for patients with known atrial fibrillation after PCI. In most individuals, oral P2Y12 inhibitor therapy combined with a direct acting oral anticoagulant appears to be the best strategy based on the available evidence. Overall, the progress in antithrombotic therapy achieved over the last seven decades is remarkable, however, there are important issues to address and progress still to be made.

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 76-84
Author(s):  
Jori E. May ◽  
Stephan Moll

Abstract Arterial thrombotic events in younger patients without a readily apparent etiology present significant diagnostic and management challenges. We present a structured approach to diagnosis with consideration of common causes, including atherosclerosis and embolism, as well as uncommon causes, including medications and substances, vascular and anatomic abnormalities, systemic disorders, and thrombophilias. We highlight areas of management that have evolved within the past 5 years, including the use of dual-pathway inhibition in atherosclerotic disease, antithrombotic therapy selection in embolic stroke of undetermined source and left ventricular thrombus, the role of closure of patent foramen ovale for secondary stroke prevention, and the thrombotic potential of coronavirus disease 2019 infection and vaccination. We conclude with a representative case to illustrate the application of the diagnostic framework and discuss the importance of consideration of bleeding risk and patient preference in determining the appropriate management plan.


Author(s):  
Axel Wester ◽  
Moman A. Mohammad ◽  
Göran Olivecrona ◽  
Jasminka Holmqvist ◽  
Troels Yndigegn ◽  
...  

Background The Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE‐DAPT) score has been shown to predict out‐of‐hospital major bleeding after myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy (DAPT). However, large validation studies have been scarce and the discriminative ability for patients with a preexisting bleeding risk factor (elderly, underweight, women, anemia, kidney dysfunction, or cancer) in a real‐world setting is unknown. Methods and Results Patients undergoing percutaneous coronary intervention for myocardial infarction between 2008 and 2017 were included from the SWEDEHEART (Swedish Web System for Enhancement of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) registry (n=66 295). The predictive value of the PRECISE‐DAPT score for rehospitalization with major bleeding during dual antiplatelet therapy was evaluated using receiver operating characteristic analyses. A high PRECISE‐DAPT score (≥25; n=13 894) was associated with increased risk of major bleeding (3.9% versus 1.8%; hazard ratio [HR], 2.2; 95% CI, 2.0–2.5; P <0.001) compared with a non‐high score (<25; n=52 401). The score demonstrated a c‐statistic of 0.64 (95% CI, 0.63–0.66). The discriminative ability of the score to further stratify bleeding risk in patients with preexisting bleeding risk factors was poor, especially in patients who are elderly (c‐statistic=0.57; 95% CI, 0.55–0.60) or underweight (c‐statistic=0.56; 95% CI, 0.51–0.61), for whom a non‐high PRECISE‐DAPT score was associated with similar bleeding risk as a high PRECISE‐DAPT score in the general myocardial infarction population. Conclusions In this nationwide population‐based study, the PRECISE‐DAPT score performed moderately in the general myocardial infarction population and poorly in patients with preexisting bleeding risk factors, where its usefulness seems limited.


2019 ◽  
Vol 5 (4) ◽  
pp. 226-236 ◽  
Author(s):  
Paul M Haller ◽  
Patrick Sulzgruber ◽  
Christoph Kaufmann ◽  
Bastiaan Geelhoed ◽  
Juan Tamargo ◽  
...  

Abstract Aims The combination of oral anticoagulation with a P2Y12 inhibitor and aspirin in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is associated with a high bleeding risk. Dual antithrombotic therapy (DAT) with omission of aspirin is a promising option to reduce bleedings, but carries a yet unknown risk of ischaemic events. We therefore sought to systematically review and analyse randomized controlled trials investigating DAT vs. triple antithrombotic therapy (TAT) in patients with AF following PCI and/or acute coronary syndrome (ACS). Methods and results We included four trials with overall 9317 patients (5039 DAT, 4278 TAT) in our analysis. Dual antithrombotic therapy was associated with a significant reduction in thrombolysis in myocardial infarction major bleeding [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.42–0.65; P = 0.0001], while the composite trial-defined ischaemic endpoint did not differ significantly between DAT and TAT (HR 0.98, 95% CI 0.79–1.22; P = 0.88). There was also no difference regarding the occurrence of myocardial infarction (MI; HR 1.16, 95% CI 0.92–1.46; P = 0.21) or stent thrombosis (HR 1.25, 95% CI 0.69–2.26; P = 0.46). Absolute numbers for MI were 131/4278 (3.1%) with TAT and 182/5039 (3.6%) with DAT, and for stent thrombosis 32/4278 (0.75%) and 52/5039 (1%), respectively. A post hoc power calculation based on the size and event rate of this meta-analysis revealed 80% power to detect a 37% and 100% increase in MI and stent thrombosis, respectively. Conclusion Dual antithrombotic therapy significantly reduces bleedings compared with TAT and seems to have a similar effect in preventing ischaemic endpoints in AF patients post-PCI or ACS. Future investigations are needed to determine its applicability specifically in patients at high risk of ischaemic outcomes.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Mapili ◽  
A S Davin ◽  
L M Villanueva

Abstract Background and objectives Peripheral artery disease (PAD) affects more than 200 million people worldwide and it is associated with an increased risk for cardiovascular morbidity and mortality. Current recommendations regarding the management of PAD have been controversial. Our meta-analysis investigated the efficacy of direct Xa inhibitor plus antiplatelet, also known as dual-pathway inhibition (DPI), on the individual components of major adverse cardiovascular events (stroke, myocardial infarction, and cardiovascular death) and major adverse limb events (amputation, restenosis, revascularization, and acute limb ischemia), the composite of MACE and MALE and its safety, in terms of bleeding, compared to antiplatelet therapy among patients with PAD. Methodology We performed a random-effects meta-analysis among patients with PAD comparing DPI to antiplatelet therapy. PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were searched from their dates of inception to August 2020 for Randomized Controlled Trials. Three studies met the inclusion criteria for final analysis. The selected studies were assessed for risk of bias using the Cochrane RoB2 tool and the overall quality of evidence was assessed using the GRADE approach. Results Among patients with PAD, DPI significantly reduces the risk of adverse limb events excluding amputation (RR 0.69, 95% CI 0.57–0.83) and composite MACE and MALE (RR 0.80, 95% CI 0.69–0.93) but significantly increases risk of major bleeding (RR 1.43, 95% CI 1.06–1.93) compared to antiplatelet therapy alone. Overall, DPI did not reduce myocardial infarction, stroke, cardiovascular death, or amputation, or increase the risk of fatal bleeding. Conclusions Among patients with PAD, DPI is more effective than antiplatelet therapy alone in preventing adverse limb events excluding amputation with an increased risk of major bleeding. We recommend the use of DPI among patients with PAD who are at a low risk of bleeding. FUNDunding Acknowledgement Type of funding sources: None.


2018 ◽  
Vol 24 (4) ◽  
pp. 496-510
Author(s):  
Daorong Pan ◽  
Xiaomin Ren ◽  
Zuoying Hu

The optimal strategy of antithrombotic therapy for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention remains to be a question to be answered. The major challenge in such population is the balance between the benefit of reduced stroke and coronary ischemic events, against the risk of increased bleeding complications. Thus, both thrombotic and bleeding risk assessments should be included into clinical decision-making process for such patients. Currently, there is limited evidence based on randomized trials with adequate power to show the superiority of any strategy in the beneficial profile of safety and efficacy, thus limited recommendations are provided by clinical guidelines. Given the recent advancement in this field, our review provided an overview of the available risk stratification schemes for stroke and bleeding risk for AF patients, discussed the multiple questions in the optimal regimens of oral antiplatelet and anticoagulation therapy, and summarized evidence and recommendations related to long-term antithrombotic therapy for AF patients receiving stent implications.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Tadashi Wada ◽  
Makoto Nakahama ◽  
Hironobu Toda ◽  
Atsuyuki Watanabe ◽  
Katsushi Hashimoto ◽  
...  

Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention increases the risk of bleeding. We studied the safety and clinical outcomes of switching from DAPT to aspirin monotherapy at 3 months after ZES implantation. We retrospectively evaluated 168 consecutive patients with coronary artery disease who had been implanted with a ZES from June 2009 through March 2010. After excluding 40 patients according to exclusion criteria such as myocardial infarction, 128 patients were divided into a 3-month DAPT group (67 patients, 88 lesions) and a 12-month conventional DAPT group (61 patients, 81 lesions). Coronary angiographic followup and clinical followup were conducted at more than 8 months and at 12 months after ZES implantation, respectively. Minor and major bleeding events, stent thrombosis (ST), and major adverse cardiac events (MACE) (death, myocardial infarction, cerebrovascular accident, target lesion revascularization, and target vessel revascularization) were evaluated. There were no statistically significant differences in the incidences of ST and MACE between the two groups. The incidence of bleeding events was significantly lower in the 3-month group than in the 12-month group (1.5% versus 11.5%, ). DAPT can be safely discontinued at 3 months after ZES implantation, which reduces bleeding risk.


Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001761
Author(s):  
Mirvat Alasnag ◽  
Tara L Jones ◽  
Yasmin Hanfi ◽  
Nicola Ryan

Balancing ischaemic and bleeding risks in high-risk populations undergoing percutaneous coronary interventions has become an everyday dilemma for clinicians. It is particularly difficult to make decisions concerning combinations and duration of antiplatelet regimens in women given the poor representation of women in trials that have shaped current practice. Several contemporary landmark trials have recently been presented at the American College of Cardiology. The trials included the Harmonising Optimal Strategy for Treatment of coronary artery diseases-EXtended Antiplatelet Monotherapy, Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention and the TicAgrelor versus CLOpidogrel in Stabilised Patients With Acute Myocardial Infarction. In this article, we summarise the main findings of these trials and include the The Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk (LEADERS FREE) in search for evidence based best practices for women patients. Although some of these trials had prespecified a subanalysis of sex differences, women constituted only 17%–30% of participants making sex-specific analyses challenging. Data suggest that women benefit from de-escalation to both ticagrelor and clopidogrel monotherapy. However, given the increased bleeding risks observed in women further randomised controlled trials are necessary to determine the most appropriate combination and duration of dual antiplatelet therapy as well as maintenance single antiplatelet therapy.


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