scholarly journals Dual Pathway Inhibition for Vascular Protection in Patients with Atherosclerotic Disease: Rationale and Review of the Evidence

2020 ◽  
Vol 120 (08) ◽  
pp. 1147-1158 ◽  
Author(s):  
Jeffrey Ian Weitz ◽  
Dominick J. Angiolillo ◽  
Tobias Geisler ◽  
Stefan Heitmeier
Keyword(s):  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Standard Of Care ◽  
Atherosclerotic Disease ◽  
Vascular Protection ◽  
Coronary Syndrome ◽  
Plaque Disruption ◽  
Dual Pathway ◽  
Artery Disease ◽  
Pathway Inhibition

AbstractDespite advances in secondary prevention strategies in patients with cardiovascular disease, the residual risk of recurrent atherothrombotic events remains high. Dual-antiplatelet therapy is the standard of care for secondary prevention in patients with acute coronary syndrome (ACS), whereas single antiplatelet therapy, generally with aspirin, is the standard of care for secondary prevention in stable patients with coronary artery disease (CAD), peripheral artery disease (PAD), or cerebrovascular disease. However, atherosclerotic plaque disruption not only triggers platelet activation but also results in thrombin generation because of tissue factor exposure. Therefore, blocking both pathways by combining antiplatelet therapy with an anticoagulant, or dual pathway inhibition (DPI), has the potential to be more effective than inhibiting either pathway alone. The benefit of DPI has been demonstrated in the ATLAS ACS 2-TIMI 51, COMPASS, and VOYAGER PAD trials, where the combination of rivaroxaban vascular dose (2.5 mg twice daily) plus aspirin significantly reduced the risk of atherothrombotic events compared with aspirin across a broad range of patients, including those with recent ACS, those with chronic CAD and/or PAD, and patients with PAD who have undergone peripheral revascularization. This article provides the rationale for this regimen in more detail, including why the DPI regimen with the rivaroxaban vascular dose was developed for vascular protection in a broad spectrum of patients with atherosclerotic disease.

scholarly journals Rivaroxaban plus aspirin for the prevention of ischaemic events in patients with cardiovascular disease: a cost-effectiveness study

2020 ◽  
Vol 27 (13) ◽  
pp. 1354-1365 ◽  
Author(s):  
Svenja Petersohn ◽  
Xavier Pouwels ◽  
Bram Ramaekers ◽  
Arina ten Cate-Hoek ◽  
Manuela Joore
Keyword(s):  
Coronary Artery Disease ◽  
Cost Effectiveness ◽  
Coronary Artery ◽  
Peripheral Arterial Disease ◽  
Antiplatelet Therapy ◽  
Arterial Disease ◽  
Dual Pathway ◽  
Artery Disease ◽  
Pathway Inhibition ◽  
Peripheral Arterial

Background Dual pathway inhibition with 2.5 mg rivaroxaban twice daily plus 100 mg aspirin once daily may be a promising alternative to 100 mg aspirin antiplatelet therapy for the prevention of cardiovascular events in patients with coronary artery disease and/or peripheral arterial disease. However, treatment costs and bleeding risks are higher, and there is another treatment option for peripheral arterial disease, 75 mg clopidogrel. A comprehensive assessment of benefits, risks and costs of dual pathway inhibition versus standard of care is needed. Methods We used a state transition model including cardiovascular, ischaemic limb and bleeding events to compare dual pathway inhibition to aspirin antiplatelet therapy in coronary artery disease, and additionally to clopidogrel antiplatelet therapy in peripheral arterial disease patients. We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a €50,000/quality-adjusted life-year threshold. Results Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were €32,109 in coronary artery disease and €26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). Incremental cost-effectiveness ratios were below €20,000 in comorbid peripheral arterial disease patients and coronary artery disease patients younger than 65 years, incremental cost-effectiveness ratios were above €50,000 in carotid artery disease patients and coronary artery disease patients older than 75 years. Conclusion Lifelong preventive treatment of coronary artery disease and peripheral arterial disease patients at risk of cardiovascular events with dual pathway inhibition improves health outcomes and seems overall cost-effective relative to aspirin antiplatelet therapy and also to clopidogrel antiplatelet therapy for peripheral arterial disease, particularly in comorbid patients, but not in older patients and in carotid artery disease patients. These findings may warrant a targeted approach.

scholarly journals The Role of Clopidogrel in 2020: A Reappraisal

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Giuseppe Patti ◽  
Giuseppe Micieli ◽  
Claudio Cimminiello ◽  
Leonardo Bolognese
Keyword(s):  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Minor Stroke ◽  
Clinical Settings ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Integral Role ◽  
Artery Disease ◽  
Ischemic Attack

Antiplatelet therapy is the mainstay of treatment and secondary prevention of cardiovascular disease (CVD), including acute coronary syndrome (ACS), transient ischemic attack (TIA) or minor stroke, and peripheral artery disease (PAD). The P2Y12 inhibitors, of which clopidogrel was the first, play an integral role in antiplatelet therapy and therefore in the treatment and secondary prevention of CVD. This review discusses the available evidence concerning antiplatelet therapy in patients with CVD, with a focus on the role of clopidogrel. In combination with aspirin, clopidogrel is often used as part of dual antiplatelet therapy (DAPT) for the secondary prevention of ACS. Although newer, more potent P2Y12 inhibitors (prasugrel and ticagrelor) show a greater reduction in ischemic risk compared with clopidogrel in randomized trials of ACS patients, these newer P2Y12 inhibitors are often associated with an increased risk of bleeding. Deescalation of DAPT by switching from prasugrel or ticagrelor to clopidogrel may be required in some patients with ACS. Furthermore, real-world studies of ACS patients have not confirmed the benefits of the newer P2Y12 inhibitors over clopidogrel. In patients with very high-risk TIA or stroke, short-term DAPT with clopidogrel plus aspirin for 21–28 days, followed by clopidogrel monotherapy for up to 90 days, is recommended. Clopidogrel monotherapy may also be used in patients with symptomatic PAD. In conclusion, there is strong evidence supporting the use of clopidogrel antiplatelet therapy in several clinical settings, which emphasizes the importance of this medication in clinical practice.

Pharmacodynamic profiles of dual-pathway inhibition with or without clopidogrel vs dual antiplatelet therapy in patients with atherosclerotic disease

2022 ◽  
Author(s):  
Mattia Galli ◽  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Latonya Been ◽  
Patrick Abou Jaoude ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Antiplatelet Therapy ◽  
Thrombin Generation ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Adenosine Diphosphate ◽  
Atherosclerotic Disease ◽  
Light Transmittance ◽  
Dual Pathway ◽  
Pathway Inhibition

Aim: Inhibition of thrombin-mediated signaling processes using a vascular dose of rivaroxaban in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there are limited data on the pharmacodynamic (PD) effects of this strategy. Methods and Results: This investigation was conducted in selected cohorts of patients (n=40) with stable atherosclerotic disease enrolled within a larger prospective PD study who were treated with either aspirin plus clopidogrel (DAPT), aspirin plus rivaroxaban 2.5 mg/bid (DPI) or DAPT plus rivaroxaban 2.5 mg/bid. Multiple PD assays assessing of markers of thrombosis were used. PD endpoints included platelet-mediated global thrombogenicity measured by light transmittance aggregometry (LTA) following stimuli with CATF [collagen‐related peptide +adenosine diphosphate (ADP) +tissue factor (TF)], markers of P2Y12 reactivity, markers of platelet aggregation using LTA following several stimuli (arachidonic acid, ADP, collagen, TF, and TRAP), thrombin generation and thrombus formation. There was no difference in platelet-mediated global thrombogenicity between groups. Rivaroxaban significantly reduced thrombin generation and was associated with a trend towards reduced TF-induced platelet aggregation. Clopidogrel-based treatments reduced markers of P2Y12 signaling and TRAP‐induced platelet aggregation. There were no differences between groups on markers of cyclooxygenase‐1 mediated activity. Conclusions: Compared with DAPT, DPI does not result in any differences in platelet-mediated global thrombogenicity, but reduces thrombin generation. These PD observations support that modulating thrombin generation by means of factor Xa inhibition in adjunct to antiplatelet therapy provides effective antithrombotic effects, supporting the efficacy and safety findings of DPI observed in clinical

scholarly journals Antiplatelet Therapy in Coronary Artery Disease: A Daunting Dilemma

2018 ◽  
Vol 7 (4) ◽  
pp. 74 ◽  
Author(s):  
Surya Chaturvedula ◽  
Daniel Diver ◽  
Aseem Vashist
Keyword(s):  
Antiplatelet Therapy ◽  
Standard Of Care ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Coronary Syndrome ◽  
Anticoagulant Drugs ◽  
Percutaneous Coronary ◽  
Artery Disease ◽  
Scientific Attention

Percutaneous coronary intervention (PCI) with stenting for the treatment of acute coronary syndrome (ACS) is the contemporary standard of care. Such treatment is followed by dual antiplatelet therapy (DAPT) comprising of aspirin and a P2Y12 inhibitor. The efficacy of this therapy has been well established but the optimal duration of DAPT remains elusive, and has thus far attracted a prodigious deal of scientific attention. The decision regarding DAPT duration can be clinically challenging in the modern era with the evolution of newer stents, more potent antiplatelet agents, and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. Major societal guidelines have emphasized comprehensive assessment of ischemic and bleeding risk, in turn recommending individualization of DAPT duration, thus encouraging “shared decision making”. The following review is aimed at critically evaluating the available evidence to help make these crucial clinical decisions regarding duration of DAPT and triple therapy.

scholarly journals Dual Pathway Inhibition with Low-Dose Direct Factor Xa Inhibition after Acute Coronary Syndromes—Why Is It Not Used in Clinical Practice?

2018 ◽  
Vol 118 (09) ◽  
pp. 1528-1534 ◽  
Author(s):  
Uwe Zeymer ◽  
Benedikt Schrage ◽  
Dirk Westermann
Keyword(s):  
Clinical Practice ◽  
Secondary Prevention ◽  
Low Dose ◽  
Factor Xa ◽  
Bleeding Complications ◽  
Direct Factor ◽  
Anti Platelet Therapy ◽  
Factor Xa Inhibition ◽  
Dual Pathway ◽  
Pathway Inhibition

AbstractThe optimal anti-thrombotic therapy for secondary prevention after an acute coronary syndrome is still a matter of debate. While current guidelines recommend dual anti-platelet therapy with aspirin and a P2Y12 inhibitor over 12 months especially in patients with stent implantation, the value of prolonged anticoagulation is still controversial. In the ATLAS-TIMI 52 trial, a low-dose direct factor Xa inhibition with rivaroxaban compared with placebo reduced the combined primary endpoint of cardiovascular mortality, myocardial infraction and stroke with an increase in major bleeding complications. This article discusses the value and problems of adding low-dose rivaroxaban to anti-platelet therapy as secondary prevention measure after an acute myocardial infarction. It will describe the pros and cons of intensified anti-platelet therapy versus dual pathway inhibition and give recommendations for different patient groups in clinical practice.

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 ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Antiplatelet Therapy ◽  
Antithrombotic Therapy ◽  
Anticoagulation Therapy ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Dual Pathway ◽  
Pathway Inhibition ◽  
Direct Acting

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.

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