Lifelong Aspirin for All in the Secondary Prevention of Chronic Coronary Syndrome: Still Sacrosanct or Is Reappraisal Warranted?

Alan P. Jacobsen, MB, BCh, BAO; Inbar Raber, MD; Cian P. McCarthy, MB, BCh, BAO; Roger S. Blumenthal, MD; Deepak L. Bhatt, MD, MPH; Ronan W. Cusack, BM, BS, BSc; Patrick W.J.C. Serruys, MD, PhD; William Wijns, MD, PhD; John W. McEvoy, MB, BCh, BAO, MHS

Disclosures

Circulation. 2020;142(16):1579-1590. 

In This Article

Abstract and Introduction

Abstract

Four decades have passed since the first trial suggesting the efficacy of aspirin in the secondary prevention of myocardial infarction. Further trials, collectively summarized by the Antithrombotic Trialists' Collaboration, solidified the historical role of aspirin in secondary prevention. Although the benefit of aspirin in the immediate phase after a myocardial infarction remains incontrovertible, a number of emerging lines of evidence, discussed in this narrative review, raise some uncertainty as to the primacy of aspirin for the lifelong management of all patients with chronic coronary syndrome (CCS). For example, data challenging the previously unquestioned role of aspirin in CCS have come from recent trials where aspirin was discontinued in specific clinical scenarios, including early discontinuation of the aspirin component of dual antiplatelet therapy after percutaneous coronary intervention and the withholding of aspirin among patients with both CCS and atrial fibrillation who require anticoagulation. Recent primary prevention trials have also failed to consistently demonstrate net benefit for aspirin in patients treated to optimal contemporary cardiovascular risk factor targets, indicating that the efficacy of aspirin for secondary prevention of CCS may similarly have changed with the addition of more modern secondary prevention therapies. The totality of recent evidence supports further study of the universal need for lifelong aspirin in secondary prevention for all adults with CCS, particularly in stable older patients who are at highest risk for aspirin-induced bleeding.

Introduction

The majority of clinicians consider aspirin essential for the secondary prevention of myocardial infarction (MI) and cardiovascular disease (CVD). The evidence supporting aspirin for secondary prevention is primarily based on studies performed in the 1970s and 1980s, which are collectively summarized in the Anti-Thrombotic Trialists' (ATT) Collaboration meta-analysis.[1–4] On the basis of this historical evidence, aspirin has long been the therapeutic foundation of the secondary prevention of CVD, on which contemporary drugs such as statins, antihypertensives, and other antithrombotics have been added.

However, the benefit of a given therapy can change over time as contemporary treatments develop and disease demographics evolve. An example of this phenomenon is the recent paradigm shift in aspirin's role in primary prevention of CVD.[5] Despite trials from the 1980s and 1990s reporting efficacy of aspirin in primary prevention, 3 randomized clinical trials published in 2018 found little to no net benefit for aspirin for this indication, and there was even a trend toward harm in older adults.[6–8] Participants in these 2018 primary prevention trials had lower blood pressure, lower cholesterol, lower smoking rates, and far higher statin use than participants enrolled in the historical aspirin trials.[5] The most recent European and American cardiovascular guidelines have downgraded previous endorsements for aspirin use in primary prevention.[5,9,10]

Aspirin-free strategies have been reviewed in select secondary prevention settings[11] and evidence has emerged that leads to further questions on whether aspirin is always necessary in secondary prevention.[12,13] Temporal changes in risk factors and concurrent treatment options that are hypothesized to have diminished the antiischemic role of aspirin in the primary prevention of CVD may also have reduced its role in contemporary secondary prevention.[14–16] Reappraisal of the ubiquitous need for aspirin in secondary prevention is further motivated by the real risk of bleeding, a particular problem for the elderly.[17,18]

In this narrative review, we discuss recent trials that inform the current use of aspirin in the secondary prevention of chronic coronary syndrome (CCS), a new term for stable coronary artery disease defined in the 2019 European Society of Cardiology guidelines.[19] Whereas a number of contemporary trials have studied discontinuing aspirin relatively early after acute coronary syndromes (ACS),[20–23] our focus is on its longer-term use in CCS (ie, the use of aspirin as a component of dual antiplatelet therapy or dual pathway inhibition during the chronic period from ≈3 to 12 months after the index coronary event). The evidence for benefit of aspirin during the active treatment of ACS remains robust.[24] Consequently, aspirin trials of patients with ACS are not considered in this review.[25] For aspirin trials that included both patients with CCS and patients with ACS, we focused our discussion on the results pertaining to the CCS subgroup. Because stroke comprises multiple distinct etiologies, the role of aspirin in secondary prevention for this indication is more complicated and is not discussed.

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