Daily aspirin is associated with new onset heart failure (HF) independent of other risk factors, according to data derived from a database with a follow-up from more than 30,000 patients who did not have HF when they were enrolled.

These data are not relevant to primary or secondary prevention of cardiovascular events but “refer only to starting aspirin for secondary prevention of HF in patients at high risk of HF or with symptomatic HF,” according to senior investigator Jan A. Staessen, MD, PhD, professor emeritus at the University of Leuven in Belgium.

In data from 30,827 patients at risk for HF enrolled in six observational studies, the hazard ratio (HR) for developing HF among those taking daily aspirin at baseline relative to those who were not was 1.26 (P ≤ .001) over 5.3 years of follow-up. In the 22,690 patients without a prior history of cardiovascular disease (CVD), the HF risk increase for exposure to daily aspirin was about the same (HR, 1.27; P = .001).

This study was launched because multiple conflicting studies have made the relationship between aspirin and HF risk unclear, according to the multinational team of authors, whose findings were published online in ESC Heart Failure.

In principle, HF is recognized as a prothrombotic condition for which an antithrombotic therapy such as aspirin would be expected to have a protective role, but the investigators pointed out that the evidence is mixed. In a population-based Danish study of 12,277 patients with new-onset HF, for example, there was no relationship seen between aspirin use and a reduction in the composite outcome of all-cause mortality, myocardial infarction, or stroke.

Aspirin Use Linked to HF Admissions

“Interestingly, this study reported that aspirin use was associated with an increased risk of readmissions for HF,” wrote the authors of the newly published data. “Uncertainty on aspirin use has been reflected in current guideline recommendations,” they added.

The population studied was drawn from the HOMAGE database, which has collated data on 46,437 participants in 21 studies. After the exclusion of studies with patients who already had HF as well as studies without information on HF incidence over time, six studies with 30,827 participants provided the basis for this analysis.

One study, ASCOT, which was randomized and blinded, served as the derivation data set. The remaining five studies, FLEMENGHO, HEALTH ABC, HULL LIFE LAB, PREDICTOR, and PROSPER, served as the validation data set.

In addition to identifying participants as aspirin users or nonusers at baseline, all of the studies had detailed baseline data on a wide variety of patient characteristics and risk factors, such as body mass index, blood cholesterol levels, blood glucose concentrations, blood pressure, and creatinine.

No patient in any trial was on an antithrombotic therapy other than aspirin at baseline.

Of the minority of patients with CVD at baseline, more than 80% had coronary heart disease. Only 2.8% of the total population had a prior myocardial infarction. In the study population overall, most (86%) had hypertension, and there was a sizeable proportion with diabetes (22%). The average age was 67 years, and 34% were women.

HF Incidence on Aspirin: 14.5/1000 Person-Years

Overall, the incidence rate of HF per 1000 person-years for the entire population before adjustment was 14.5 in the group on daily aspirin versus 5.9 in the nonaspirin group. These absolute rates were lower in the discovery data set than in the validation set, but the relative differences in HF incidence rates for those who were versus those who were not on aspirin at baseline were similar.

Numerous sensitivity analyses supported the basic conclusions. This not only included one omitting patients with a history of CVD, but another that excluded patients who developed HF within the first 2 years. Stratified analyses looking for overall consistency across variables showed increased risk of new onset heart failure among those taking daily aspirin regardless of relative age, body weight, or blood pressure levels.

The most important limitation of this study was that it evaluated data taken from studies not originally designed to test the study hypothesis. In addition, only baseline data were available, so the drugs that patients took over the course of follow-up are unknown. However, the authors believe these data have a clinical message.

Given the consistency of these results, “our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF,” the investigators concluded.

“If such treatment is initiated in these patients, use low-dose aspirin,” Staessen told MDedge.

Aspirin for CVD Versus HF Risk

Many patients take low-dose aspirin to prevent the types of cardiovascular events, such as MI, that lead to heart failure. In attempting to address a controversy regarding aspirin and risk of new onset heart failure, it appears to create another regarding CVD risk reduction.

Deepak L. Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Health, Boston, expressed some reluctance in applying these data to routine practice.

“It is important to emphasize that this pooled analysis draws upon six observational studies, not randomized trials of aspirin,” Bhatt said.

He called these findings “provocative,” but he said they “would need to be confirmed in databases of already completed randomized trials of aspirin versus a control before being actionable.” For Bhatt, one obstacle to a change in practice based on these data is that, “to my knowledge, no such signal [of a relationship between aspirin and incident heart failure] exists in the cumulative randomized data.”

Staessen reported no potential conflicts of interest for this study. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PLx Pharma, for which he performs aspirin-related research.

ESC Heart Fail. Published online November 22, 2021. Full text

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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