Dual pathway inhibition in atherothrombosis prevention: yes, now we can!

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.

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A dual pathway inhibition strategy using BKM120 combined with vemurafenib is poorly tolerated in BRAF V600 E/K mutant advanced melanoma

Pigment Cell & Melanoma Research ◽

10.1111/pcmr.12777 ◽

2019 ◽

Vol 32 (4) ◽

pp. 603-606 ◽

Cited By ~ 2

Author(s):

Alain Patrick Algazi ◽

Julia Rotow ◽

Christian Posch ◽

Susana Ortiz‐Urda ◽

Alyson Pelayo ◽

...

Keyword(s):

Advanced Melanoma ◽

Dual Pathway ◽

Pathway Inhibition

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CSIG-41. ONCOGENE ADDICTION SWITCH FROM NOTCH TO PI3K REQUIRE SIMULTANEOUS TARGETING OF DUAL PATHWAY INHIBITION IN GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noy148.207 ◽

2018 ◽

Vol 20 (suppl_6) ◽

pp. vi52-vi52

Author(s):

Norihiko Saito ◽

Kazuya Aoki ◽

Nozomi Hirai ◽

Ryo Suzuki ◽

Satoshi Fujita ◽

...

Keyword(s):

Oncogene Addiction ◽

Dual Pathway ◽

Pathway Inhibition

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

Thrombosis and Haemostasis ◽

10.1055/s-0040-1714212 ◽

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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Rivaroxaban plus aspirin for cardiovascular protection: Rationale for the vascular dose and dual pathway inhibition

Thrombosis Research ◽

10.1016/j.thromres.2019.09.033 ◽

2019 ◽

Vol 184 ◽

pp. 44-49 ◽

Cited By ~ 1

Author(s):

Eduardo Ramacciotti ◽

Jeffrey I. Weitz

Keyword(s):

Cardiovascular Protection ◽

Dual Pathway ◽

Pathway Inhibition

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Inhibition of Eicosanoid Synthesis and Potential Therapeutic Benefits of ‘Dual Pathway Inhibition’

Pharmacology & Toxicology ◽

10.1111/j.1600-0773.1994.tb01990.x ◽

1994 ◽

Vol 75 ◽

pp. 9-13 ◽

Cited By ~ 6

Author(s):

K. Lauritsen ◽

L. S. Laursen ◽

J. Kjeldsen ◽

K. Bukhave ◽

J. Rask-Madsen

Keyword(s):

Eicosanoid Synthesis ◽

Therapeutic Benefits ◽

Dual Pathway ◽

Pathway Inhibition

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Unexplained arterial thrombosis: approach to diagnosis and treatment

Hematology ◽

10.1182/hematology.2021000235 ◽

2021 ◽

Vol 2021 (1) ◽

pp. 76-84

Author(s):

Jori E. May ◽

Stephan Moll

Keyword(s):

Bleeding Risk ◽

Management Plan ◽

Left Ventricular ◽

The Past ◽

Common Causes ◽

Dual Pathway ◽

Diagnostic Framework ◽

Pathway Inhibition ◽

Structured Approach

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.

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