Monotherapy for nonvalvular A-fib with stable CAD?

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doi:doi: 10.12788/jfp.0289

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Monotherapy for nonvalvular A-fib with stable CAD?

J Fam Pract. 2021 October;70(8):403-404,407 | doi: 10.12788/jfp.0289

By

Thomas P. Garigan, MD, MA

John S. Earwood, MD

Michal Poplawski, MD

A meta-analysis found oral anticoagulant (OAC) monotherapy provided efficacy comparable to OAC plus single antiplatelet therapy—with lower bleeding risk.

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PRACTICE CHANGER

Recommend the use of a single oral anticoagulant (OAC) over combination therapy with an OAC and an antiplatelet agent for patients with nonvalvular atrial fibrillation (AF) and stable ischemic heart disease (IHD). Doing so may confer the same benefits with fewer risks.

STRENGTH OF RECOMMENDATION

A: Meta-analysis of 7 trials¹

Lee SR, Rhee TM, Kang DY, et al. Meta-analysis of oral anticoagulant monotherapy as an antithrombotic strategy in patients with stable coronary artery disease and nonvalvular atrial fibrillation. Am J Cardiol. 2019;124:879-885. doi: 10.1016/j.amjcard.2019.05.072

References

1. Lee SR, Rhee TM, Kang DY, et al. Meta-analysis of oral anticoagulant monotherapy as an antithrombotic strategy in patients with stable coronary artery disease and nonvalvular atrial fibrillation. Am J Cardiol. 2019;124:879-885. doi: 10.1016/j.amjcard.2019.05.072

2. Fihn SD, Gardin JM, Abrams J, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American College of Physicians; American Association for Thoracic Surgery; Preventive Cardiovascular Nurses Association; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60:e44-e164.

3. Whitlock EP, Burda BU, Williams SB, et al. Bleeding risks with aspirin use for primary prevention in adults: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:826-835. doi: 10.7326/M15-2112

4. McNeil JJ, Nelson MR, Woods RL, et al; ASPREE Investigator Group. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379:1519-1528. doi: 10.1056/NEJMoa1803955

5. Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692-694. doi: 10.1111/j.1538-7836.2005.01204.x

6. Yasuda S, Kaikita K, Akao M, et al; AFIRE Investigators. Antithrombotic therapy for atrial fibrillation with stable coronary disease. N Engl J Med. 2019;381:1103-1113. doi: 10.1056/NEJMoa1904143

7. Kumbhani DJ, Cannon CP, Beavers CJ, et al. 2020 ACC expert consensus decision pathway for anticoagulant and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;77:629-658. doi: 10.1016/j.jacc.2020.09.011

8. Berry NC, Mauri L, Steg PG, et al. Effect of lesion complexity and clinical risk factors on the efficacy and safety of dabigatran dual therapy versus warfarin triple therapy in atrial fibrillation after percutaneous coronary intervention: a subgroup analysis from the REDUAL PCI trial. Circ Cardiovasc Interv. 2020;13:e008349. doi: 10.1161/CIRCINTERVENTIONS.119.008349

ILLUSTRATIVE CASE

A 67-year-old man with a history of coronary artery stenting 7 years prior and nonvalvular AF that is well controlled with a beta-blocker comes in for a routine health maintenance visit. You note that the patient takes warfarin, metoprolol, and aspirin. The patient has not had any thrombotic or bleeding events in his lifetime. Does this patient need to take both warfarin and aspirin? Do the antithrombotic benefits of dual therapy outweigh the risk of bleeding?

Antiplatelet agents have long been recommended for secondary prevention of cardiovascular (CV) events in patients with IHD. The goal is to reduce the risk of coronary artery thrombosis.² Many patients with IHD also develop AF and are treated with OACs such as warfarin or direct oral anticoagulants (DOACs) to prevent thromboembolic events.

There has been a paucity of data to determine the risks and benefits of OAC monotherapy compared to OAC plus single antiplatelet therapy (SAPT). Given research that shows increased risks of bleeding and all-cause mortality when aspirin is used for primary prevention of CV disease,^3,4 it is prudent to examine if the harms of aspirin outweigh its benefits for the secondary prevention of acute coronary events in patients already taking antithrombotic agents.

STUDY SUMMARY

Reduced bleeding risk, with no difference in major adverse cardiovascular events

This study by Lee and colleagues¹ was a meta-analysis of 8855 patients with nonvalvular AF and stable coronary artery disease (CAD), from 6 trials comparing OAC monotherapy vs OAC plus SAPT. The meta-analysis involved 3 studies using patient registries, 2 cohort studies, and an open-label randomized trial that together spanned the period from 2002 to 2016. The longest study period was 9 years (1 study) and the shortest, 1 year (2 studies). Oral anticoagulation consisted of either vitamin K antagonist (VKA) therapy (the majority of the patients studied) or DOAC therapy (8.6% of the patients studied). SAPT was either aspirin or clopidogrel.

The primary outcome measure was major adverse CV events (MACE). Secondary outcome measures included major bleeding, stroke, all-cause mortality, and net adverse events. The definitions used by the studies for major bleeding were deemed “largely consistent” with the International Society on Thrombosis and Haemostasis major bleeding criteria, ie, fatal bleeding, symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular causing compartment syndrome), or a drop in hemoglobin (≥ 2 g/dL or requiring transfusion of ≥ 2 units of whole blood or red cells).⁵

This study strongly suggests that there is a large subgroup of patients with stable CAD for whom single antiplatelet therapy should not be prescribed as a preventive medication.

There was no difference in MACE between the monotherapy and OAC plus SAPT groups (hazard ratio [HR] = 1.09; 95% CI, 0.92-1.29). Similarly, there were no differences in stroke and all-cause mortality between the groups. However, there was a significant association of higher risk of major bleeding (HR = 1.61; 95% CI, 1.38-1.87) and net adverse events (HR = 1.21; 95% CI, 1.02-1.43) in the OAC plus SAPT group compared with the OAC monotherapy group.

This study’s limitations included its low percentage of patients taking a DOAC. Also, due to variations in methods of reporting CHA₂DS₂-VASc and HAS-BLED scores among the studies (for risk of stroke in patients with nonrheumatic AF and for risk of bleeding in AF patients taking anticoagulants), this meta-analysis could not determine if different outcomes might be found in patients with different CHA₂DS₂-VASc and HAS-BLED scores.

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