scholarly journals PHARMACODYNAMIC PROFILES OF DUAL ANTIPLATELET THERAPY VERSUS DUAL PATHWAY INHIBITION IN PATIENTS WITH ATHEROSCLEROTIC DISEASE MANIFESTATIONS

2021 ◽  
Vol 77 (18) ◽  
pp. 1070
Author(s):  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Latonya Been ◽  
Patrick Abou Jaoude ◽  
Andrea Rivas ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Atherosclerotic Disease ◽  
Dual Pathway ◽  
Pathway Inhibition

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.

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 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.

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 Clopidogrel plus Aspirin for Symptomatic Intracranial Atherosclerotic Stenosis: A Pilot Study

2016 ◽  
Vol 5 (3-4) ◽  
pp. 157-164 ◽  
Author(s):  
Tareq Kass-Hout ◽  
Melanie Winningham ◽  
Omar Kass-Hout ◽  
Laura Henriquez ◽  
Frank Tong ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Medical Management ◽  
Dual Antiplatelet Therapy ◽  
Recurrent Stroke ◽  
Intracranial Stenosis ◽  
Atherosclerotic Disease ◽  
Vascular Events ◽  
Intracranial Atherosclerotic Disease ◽  
Atherosclerotic Stenosis ◽  
Aggressive Medical Management

Background and Purpose: There are limited data on the optimal duration of dual antiplatelet therapy for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic disease. Methods: Consecutive patients presenting with high-grade (70-99%) symptomatic intracranial stenosis from January 1, 2011, to December 31, 2013, and evaluated within 30 days of the index event were eligible for this analysis. All patients underwent treatment with aspirin plus clopidogrel for a target duration of 12 months along with aggressive medical management based on the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) protocol; all patients were given gastrointestinal prophylaxis for the duration of their aspirin and clopidogrel treatment. Clinical and safety outcomes of our cohort were compared with the medical arm of the SAMMPRIS trial cohort (n = 227). Results: Our cohort included 25 patients that met the inclusion criteria. Achievement of blood pressure and LDL cholesterol targets were similar between our cohort and the SAMMPRIS cohort. At 1 year, the rates of stroke, myocardial infarction or vascular death were 0% in our cohort and 16% in the SAMMPRIS cohort (p = 0.03). At 1 year, major bleeding rates were similar between our cohort and the SAMMPRIS cohort (4 vs. 2.2%, p = 1.0). Conclusion: A prolonged course of dual antiplatelet therapy for symptomatic intracranial atherosclerotic disease may be associated with less vascular events with no increase in hemorrhagic complications.

Dual antiplatelet therapy (PEGASUS) vs. dual pathway (COMPASS): a head-to-head in vitro comparison

Platelets ◽  
2021 ◽  
pp. 1-6
Author(s):  
Cole R. Clifford ◽  
Richard G. Jung ◽  
Benjamin Hibbert ◽  
Aun Yeong Chong ◽  
Marie Lordkipanidzé ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Dual Pathway ◽  
In Vitro Comparison

scholarly journals The efficacy and safety of dual-pathway inhibition therapy among patients with peripheral arterial disease – a meta-analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Mapili ◽  
A S Davin ◽  
L M Villanueva
Keyword(s):  
Myocardial Infarction ◽  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Acute Limb Ischemia ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Dual Pathway ◽  
Pathway Inhibition

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.

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