Low-Dose Aspirin in Heart Failure Sans Atrial Fib: Recommended or Not?

February 16, 2018

Long-term, low-dose aspirin had no effect on risk for death or ischemic events after a heart failure (HF) hospitalization in a large cohort study of patients without a history of atrial fibrillation (AF).

Nor did those on low-dose aspirin show an increased risk for hospitalization for bleeding. But their risks for myocardial infarction (MI) and HF readmission were elevated compared with nonusers of aspirin during the median follow-up of 1.7 years.

These findings, based on an observational study that used propensity matching in an effort to control for possible confounders in a cohort of more than 12,000 patients from across Denmark, "cast further doubt on the benefit associated with the use of aspirin in patients with HF," conclude authors of a report published January 29 in JACC: Heart Failure.

Short-term low-dose aspirin after an MI is well known to be cardioprotective, but there isn't solid evidence supporting long-term use in patients with ischemic heart disease or HF of any kind, according to the authors, led by Christian Madelaire, MD, Copenhagen University Hospital, Hellerup, Denmark.

Yet long-term low-dose aspirin is widely prescribed in HF, observe both the authors of the report and an accompanying editorial from John GF Cleland, MD, Imperial College London, United Kingdom.

Both publications cite a litany of underpowered and inconclusive trials, at least some of which attempt to clarify the issue, with varying results, going back more than a decade. These include WARCEF, WASH, WATCH, HELAS, and other studies.

"Importantly, international guidelines have not reached a consensus on recommending aspirin for patients with heart failure, even if they have coronary artery disease," Cleland writes.

Much of Cleland's editorial is a polemic against the longstanding prevalent use of low-dose aspirin in cardiology practice, even some uses in ischemic heart disease, a position for which he is well known.

For example, "There are no randomized, placebo-controlled trials, contemporary or historical, showing that aspirin given for longer than 28 days, at any dose, reduces cardiovascular mortality after a myocardial infarction," Cleland writes.

"Prescribing aspirin, long-term, has become at least a habit and perhaps an addiction," he asserts. "Aspirin is a fine example of the mess created by people jumping to premature conclusions based on wishful thinking and flawed data."

"Useless but Not Harmful"

Regarding the current study, which isn't a randomized trial among other limitations, Cleland notes, the results for mortality, stroke, and hospitalization for bleeding "suggest that aspirin might be useless but not harmful."

However, "the increased risk of heart failure hospitalization is consistent with many, although not all, previous analyses and, if true, equates to a number needed to harm of just 48," he writes. "The effect on myocardial infarction could just reflect residual confounding but certainly does not provide evidence of benefit from aspirin."

The Danish cohort study "isn't moving the needle for me," Paul A Gurbel, MD, Inova Heart and Vascular Institute, Falls Church, Virginia, told theheart.org | Medscape Cardiology.

True, the study doesn't support the use of low-dose aspirin in the patients it included, he said. "But it doesn't mean aspirin is not efficacious. This study has way too many limitations for us to say we shouldn't use aspirin."

Gurbel agrees that no adequately powered trial has pointed to whether low-dose aspirin can clinically benefit patients without AF who are discharged after experiencing HF decompensation.

"But you have to look at the evidence in patients who have prior myocardial infarction. And that evidence, I would submit, is to give them an antiplatelet agent, and not to leave them naked." Gurbel added that platelet activation is heightened in patients with HF.

"To say, because they have decompensated heart failure, they're not going to benefit from aspirin even if they have ischemic heart disease? And even if they've proven they can form a clot in their coronary arteries? I think that's a dangerous message."

Parity After Propensity Matching

The analysis covered 12,277 patients in Denmark discharged from a first hospitalization for HF from 2007 to 2012, who had no known history of AF or other arrhythmia, had no history of oral anticoagulation, and had survived at least the next 90 days.

In an unadjusted analysis, the primary endpoint occurred in 39.6% of patients who were receiving aspirin after discharge and in 38.9% of those not receiving long-term aspirin.

In an analysis that matched 3840 of those receiving long-term aspirin against the same number of non–aspirin users based on propensity scores that accounted for demographic characteristics, HF severity, comorbidities, and other medical therapy, the risk for the primary endpoint was not significantly increased in aspirin users. However, they showed increases in risk for admission for MI or for HF.

Table. Hazard Ratios for Outcomes in Aspirin Users vs Propensity-Matched Non–Aspirin Users

Endpoints Hazard Ratio (95% CI) P Value
Death or admission for MI or stroke 0.98 (0.91–1.05) .53
Death from any cause 0.98 (0.91–1.05) .51
Admission for MI 1.34 (1.08–1.67) .009
Admission for stroke 0.92 (0.74–1.15) .47
HF readmission 1.10 (1.01–1.19) .03
Admission for bleeding 1.13 (0.94–1.35) .18


Gurbel pointed to what he sees as a major limitation of the trial: omission from the analysis of clinical events during the first 90 days after hospital discharge.

"By doing this, it avoided the possibility that some members of the study population, taking aspirin, could carry a prescription from before the initial admission over into the study period and accidentally appear as non-aspirin users," the authors explain. Low-dose aspirin in Demark is "typically prescribed in packages of 100 pills," they note, enough for just over 90 days.

The authors acknowledge that by counting events only after 90 days, they missed some primary endpoints in patients otherwise eligible for the analysis. Among those discharged from the hospital, the 90-day rate of death from any cause, MI, or stroke was almost 12%.

Gurbel also pointed out another limitation: that only about 28% of the cohort had ischemic heart disease.

"You have to extrapolate all the evidence in favor of aspirin," he said. "It's not in a heart failure population, but you apply it to the heart failure population until you have an adequately sized and powered clinical trial. And who knows if we'll ever see that."

Madelaire has no relevant relationships. Disclosures for the other authors are in the report. Cleland discloses receiving research funding and honoraria for advisory boards and speaking from Bayer. Gurbel discloses receiving honoraria or consulting fees from Janssen, Bayer, World Medical, Aralez, Haemonetics, Rockpointe, and Ionis and grants from Amgen, Janssen, Bayer, Merck, Medicure, Werfen, idorsia, and Haemonetics.

JACC Heart Fail. 2018;6:156-167, 168-171. Abstract, Editorial 

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