Synergy of Dual Pathway Inhibition in Chronic Cardiovascular Disease

Circ Res. 2019 Feb;124(3):416-425. doi: 10.1161/CIRCRESAHA.118.313141.

Abstract

Although acetylsalicylic acid is of proven benefit for secondary prevention in patients with cardiovascular disease, the risk of recurrent ischemic events remains high. Intensification of antithrombotic therapy with more potent antiplatelet drugs, dual antiplatelet therapy, or vitamin K antagonists further reduces the risk of major adverse cardiovascular events compared with acetylsalicylic acid alone but increases the risk of bleeding without reducing mortality. In patients with prior coronary artery disease or peripheral arterial disease the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial revealed that compared with acetylsalicylic acid alone, dual pathway inhibition with low-dose rivaroxaban (2.5 mg twice-daily), an oral factor Xa inhibitor, plus acetylsalicylic acid reduced major adverse cardiovascular event by 24%, major adverse limb events by 47%, and mortality by 18%. Major bleeding was increased by 70%, but there was no increase in fatal or intracranial bleeding. This article (1) reviews the results of the COMPASS trial, (2) explains why dual pathway inhibition is superior to antiplatelet or anticoagulant therapy alone, (3) compares the results with rivaroxaban plus aspirin with those with other antithrombotic regimens, and (4) provides insight into how best to apply the COMPASS results into practice.

Keywords: cardiovascular disease; coronary artery disease; peripheral arterial disease; rivaroxaban; secondary prevention.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Atrial Fibrillation / complications
  • Cardiovascular Diseases / prevention & control*
  • Chronic Disease
  • Coronary Artery Disease / drug therapy
  • Drug Therapy, Combination / methods
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control
  • Peripheral Arterial Disease / drug therapy
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Recurrence
  • Research Design
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / therapeutic use*
  • Secondary Prevention
  • Stroke / prevention & control

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Rivaroxaban
  • Aspirin