Drugs That Worsen Heart Failure Common in Hospitalized HF

Batya Swift Yasgur, MA, LSW

November 11, 2019

An array of commonly prescribed medications that exacerbate heart failure (HF) are often continued or even initiated following an HF hospitalization, a new study shows.

Investigators analyzed the use of major HF-exacerbating medications, both at hospital admission and at discharge, in more than 500 older adults hospitalized for HF during more than 700 hospital admissions.

Close to half of hospitalized patients received HF-exacerbating medications either prior to admission or during hospitalization. Moreover, among those taking these drugs, their use between admission and discharge decreased in only 17% and actually increased in 12% of patients.

"Medications that can worsen heart failure are commonly used in older adults with heart failure," lead author Parag Goyal, MD, MSc, assistant professor of medicine, division of cardiology, and director of the HFpEF Program at Weill Cornell Medicine, New York City, told theheart.org | Medscape Cardiology.

"Prior work in this area, coupled with findings from our study, highlight the need for improved processes of medication review and medication optimization — which should include both prescribing and, in some cases, de-prescribing — to ensure the safety and well-being of our patients with heart failure," he said.

Goyal added that many medications that can worsen HF are actually first-line treatment for other common comorbidities found in older adults — for example, ibuprofen for pain or albuterol for chronic obstructive pulmonary disease (COPD).

"We need more research to better understand the negative effects of these agents and how best to deal with these scenarios of 'therapeutic competition,' " he said.

The study was published online November 6 in JACC Heart Failure.

Opportune Time

An American Heart Association (AHA) 2016 Scientific Statement on Drugs That May Cause or Exacerbate Heart Failure contains a comprehensive list of medications thought to worsen HF; however, "the prevalence of these medications among hospitalized older adults — a population particularly vulnerable to drug-related adverse events — is unknown," the authors write.

HF hospitalization and discharge could potentially be an "opportune time to improve medication-prescribing practice," but it is "unknown" whether this opportunity is actually used to decrease the use of HF-exacerbating medications.

"Outcomes are particularly poor for older adults following a hospitalization for heart failure, and while efforts to improve outcomes have primarily focused on medications that are beneficial in heart failure — guideline-directed medical therapy — we were interested in characterizing patterns of harmful medications," Goyal said.

To investigate the question, the researchers studied the medical records of 558 unique individuals (median age 76 years [IQR 72 – 83], 44% female, 34% black) as well as 723 unique hospitalizations between 2003 and 2014, comparing medications patients were taking at admission to those they were taking upon discharge.

Participants were drawn from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study — a national geographically diverse prospective observational cohort of community-dwelling adults age 45 years or older.

Data were drawn from four sources: the REGARDS baseline assessment; medical charts from each HF-adjudicated hospitalization; American Hospital Association annual survey database; and Medicare's Hospital Compare website.

The researchers collected an array of demographic and baseline characteristics obtained during enrollment in REGARDS and examined cardiovascular conditions and comorbidities for which HF-exacerbating medications may be prescribed, as well as left ventricular ejection fraction (LVEF), length of hospital stay, cardiology consultation, ICU stay, and hospitalization year.

For the purposes of the study, they grouped patients with HF with borderline ejection fraction (LVEF 40% – 50%) together with those with HF with preserved ejection fraction (HFpEF).

HF-exacerbating medications listed in the AHA Scientific Statement were classified as having "major," "moderate," or "minor" exacerbating potential and each was ascribed a level of evidence, based on available literature.

  • Level A evidence: based on multiple populations through meta-analyses and/or multiple randomized trials

  • Level B evidence: based on single randomized trial or nonrandomized studies only

  • Level C evidence: based on expert opinions, case studies, or standard of care.

Overlooked Opportunity

Close to half of the patients (47%) had comorbid diabetes, while 38% had COPD/asthma, and 27% had osteoarthritis.

Polypharmacy was common, with patients taking median number of medications of 9 (IQR 6 – 12) at admission and 10 (IQR 8 – 13) at discharge.

Overall, the prevalence of HF-exacerbating medications at hospital discharge was lower than at hospital admission (36% and 41%, respectively), with these medications more likely to be used by patients who were younger and had several comorbid conditions, including COPD/asthma, diabetes, and mood disorder.

Differences between medication prevalence at admission and discharge by type of medication are listed below.

Table. Prevalence of HF-Exacerbating Medications


Level A

Level B

Level C

Hospital Admission (%)




Hospital Discharge (%)





At admission, the most common HF-exacerbating medications taken by patients were albuterol, diltiazem, and nonsteroidal anti-inflammatory drugs (NSAIDs), all Level B agents, as well as metformin, a Level C agent.

Albuterol, diltiazem, and metformin remained the most common HF-exacerbating medications at discharge.

Albuterol showed the greatest increase in prevalence between admission and discharge (16% to 22%), while NSAIDs showed the greatest decreased in prevalence (9% to 3%).

Analysis of unique hospitalizations yielded similar findings. 

Of the total patient cohort, 51% were not prescribed an HF-exacerbating medication either at admission or at discharge. Of the remainder, 17% experienced a decrease and 12% experienced an increase in the number of HF-exacerbating medications between admission and discharge, while the number of medications remained unchanged in 19%.

Notably, the authors say, 9% of patients were initiated on an HF-exacerbating medication after not taking any at admission. On the other hand, 13% of patients who were taking 1 or more HF-exacerbating medications at admission had complete discontinuation of all these agents at discharge.

There was a 31% prevalence of potentially harmful prescribing practices (defined as either the continuation of the same number of HF-exacerbating medications or an increase in the number between hospital admission and discharge).

In multivariate analysis, the researchers found that diabetes (odds ratio [OR] 1.8; 95% confidence interval [CI], 1.18 - 2.75) and small hospital size (OR 1.93; 95% CI, 1.18 - 3.16) were "the strongest independently associated determinants of harmful prescribing practice." 

"By showing that the use of medications that can worsen HF is common, we have identified a potentially overlooked opportunity to improve post-hospitalization outcomes of older adults with HF," Goyal said.

Common Scenario

Commenting on the study for theheart.org | Medscape Cardiology, Christopher O'Connor, MD, president of Inova Heart and Vascular Institute, Falls Church, Virginia, called it an "important study" that "highlights a very common scenario."

O'Connor, who is also the editor-in-chief of JACC Heart Failure and was not involved in the study, said, "We have done well in developing new therapies to reduce HF hospitalization, but less attention has been paid to the use of medications that increase the probability of an HF exacerbation, but are often used to treat other comorbidities."

He emphasized the role of education in bringing awareness of this concern to practitioners.

"The publication of a paper like this and further research heightens the awareness and increases the exposure of this problem on a national and global level," O'Connor said.

Additionally, the electronic health record, "can flag medications that patients take and note for providers that they may be associated with exacerbation, and help find alternatives that are less problematic in these patients," O'Connor suggested.

The study was supported by grants from the National Heart, Lung, and Blood Institute and the National Institute on Aging. Goyal disclosed research support from Amgen for unrelated research. The other authors’ disclosures are listed in the original article. O'Connor has disclosed no relevant financial relationships.

JACC Heart Failure. Published online November 6, 2019. Abstract

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