What is the clinical evidence from this study?

Study design: Review. Population: Cardiovascular diseases beyond atrial fibrillation (ESUS, ACS, stable atherosclerotic vascular disease, CHF, VTE). Intervention: Non-Vitamin K antagonist oral anticoagulants (NOACs) vs. Standard of care (aspirin, warfarin, enoxaparin, placebo).

September 30, 2019Open Access

Non-Vitamin K Antagonist Oral Anticoagulants in Medical Conditions at High Risk of Thromboembolism beyond Atrial Fibrillation

Key Result

Non-vitamin K antagonist oral anticoagulants have proven efficacy for VTE prophylaxis, acute VTE, and concomitant ACS and AF, but failed to show benefit over aspirin in embolic stroke of undetermined source.

Structured PICO

Do NOACs reduce thromboembolic events compared to standard therapy in patients with medical conditions at high risk of thromboembolism beyond atrial fibrillation?

Population

Patients with medical conditions at high risk of venous or arterial thrombosis other than atrial fibrillation, including hip or knee arthroplasty, acute venous thromboembolism (VTE), cancer-associated VTE, acute coronary syndrome (ACS), stable atherosclerotic vascular disease, chronic heart failure, and embolic stroke of undetermined source (ESUS).

Intervention

Non-Vitamin K antagonist oral anticoagulants (NOACs) as a class

Comparator

Standard therapy (including aspirin, warfarin, enoxaparin, or placebo depending on the specific medical condition)

Outcome

Thromboembolic events (including recurrent stroke, VTE, myocardial infarction, cardiovascular death) and major bleedingcomposite

This review highlights that while NOACs are highly effective for VTE and certain ACS/stable cardiovascular disease scenarios, they do not currently show superiority over aspirin for preventing recurrent stroke in unselected ESUS patients.

Limitations

Heterogeneity of stroke mechanisms in ESUS likely accounts for the neutral results in ESUS trials
Indirect comparisons between different NOAC trials limit valid interpretation
Exclusion of patients with recent stroke in some trials limits the application of findings to the stroke population
Some trials were not designed to primarily assess the efficacy of ischemic event outcomes

Abstract

Non-Vitamin K antagonist oral anticoagulants (NOACs) have been extensively investigated in medical conditions at high risk of venous or arterial thrombosis other than atrial fibrillation (AF), including hip or knee arthroplasty, acute venous thromboembolism (VTE), cancer-associated VTE, acute coronary syndrome (ACS), stable atherosclerotic vascular disease, chronic heart failure, and embolic stroke of undetermined source (ESUS). Two large ESUS trials failed to show the benefit of rivaroxaban or dabigatran, and large randomized controlled trial (RCT) data of NOACs are lacking for another potential candidates of patent foramen ovale-related stroke, acute ischemic stroke, and cerebral venous thrombosis. On the other hand, high quality evidences of NOACs have been compiled for VTE prophylaxis after hip or knee arthroplasty, acute VTE, cancer-associated VTE, and concomitant ACS and AF, which have been reflected in clinical practice guidelines. In addition, RCTs showed the benefit of very low dose rivaroxaban in combination with antiplatelet therapy in patients with ACS and in those with stable cardiovascular disease. This article summarizes the accumulated evidences of NOACs in cardiovascular diseases beyond AF, and aims to inform healthcare providers of optimal regimens tailored to individual medical conditions and help investigators design future clinical trials.

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