By Michael H. Crawford, MD

Professor of Medicine, Associate Chief for Education, Division of Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: In a large, diverse cohort of Medicare patients hospitalized for heart failure exacerbations, almost half were on medications known to exacerbate heart failure; more than one-third were on these agents at discharge.

SOURCE: Goyal P, Kneifati-Hayek J, Archambault A, et al. Prescribing patterns of heart failure exacerbating medications following a heart failure hospitalization. JACC Heart Fail 2020;8:25-34.

Hospital admissions and readmissions due to heart failure (HF) exacerbations are common. Considerable national efforts have been invested in preventing them. However, little attention has been paid to concomitant therapy known to exacerbate HF.

The authors of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study identified Medicare beneficiaries > age 65 years with an adjudicated HF hospitalization between 2003 and 2014. In this diverse cohort, only hospitalizations > 90 days after eligible hospitalizations were included since earlier hospitalizations were likely to feature few medication changes. The HF-exacerbating medications were taken from the 2016 American Heart Association (AHA) Scientific Statement list of directly toxic medications and those that can exacerbate underlying myocardial dysfunction.1 Only those medications classified as major exacerbating agents due to the potential for their life-threatening effects were studied.

A total of 558 unique patients with 723 unique hospitalizations were included. Their median age was 76 years; 44% were women, and 34% were black. The prevalence of HF-exacerbating medications was 41% at hospital admission and 36% at discharge. These patients were more likely to exhibit several comorbid conditions. The most frequently prescribed medications were albuterol, metformin, nonsteroidal anti-inflammatory drugs (NSAIDs), and diltiazem. During hospitalization, 17% reduced intake of their HF-exacerbating drugs, 19% took the same amount, 12% took more, and 51% were not taking any of these medications at admission or discharge. A multivariate analysis showed the factors most associated with potentially harmful prescribing were 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). The authors concluded that HF-exacerbating medications are initiated frequently or continued in Medicare patients admitted for HF.


The emphasis in HF management programs has been on guideline-based optimal medical therapy, not on avoiding drugs that could exacerbate HF. Thus, it is perhaps not surprising that almost half of older patients admitted for HF are on such medications. What is perhaps surprising is that potentially harmful drugs often are continued or even added during hospitalizations, such that 36% are discharged on these drugs. When I teach trainees about why patients experience HF exacerbation, I usually mention the five most common reasons: ischemia, arrhythmias, dietary indiscretion, medication noncompliance, and stress (e.g., infection). Now, we should add potentially harmful medications.

The AHA document lists dozens of agents with evidence for a casual role in HF exacerbations. Goyal et al focused on 22 such agents with the highest risk for harm. However, the level of evidence was not the same for each. For example, trastuzumab (Herceptin), a chemotherapy agent, carries level A evidence, NSAIDs level B, and metformin level C. Diabetes was one of the most common comorbidities leading to the prescription of potentially harmful drugs. Fortunately, there are newer drugs for diabetes that may help prevent HF (e.g., sodium-glucose transporter inhibitors). Obstructive airway disease was another common comorbidity, occurring in 30% of the Goyal et al cohort. Most drugs used for these pulmonary conditions can exacerbate HF (e.g., steroids, albuterol, antibiotics). These considerations point out one downside of disease-specific guidelines: therapeutic competition.

The strengths of this study were that the results are generalizable due to the diversity of the patients and the 380 hospitals studied. Weaknesses included the consideration of only standing medication orders, which may have underestimated the number of patients receiving bronchodilators and NSAIDs. Some drugs, such as citalopram, are only toxic at extremely high doses or with significant renal dysfunction; their significance may be overestimated. Clearly, this study shows that medication list management in hospitalized HF patients is suboptimal. This may be an area where the electronic medical record could help by flagging potentially harmful drugs if HF is on the admitting diagnoses list. All we need is another warning signal on the computer, so maybe there is a better way. There are pharmacists on our inpatient teams, and I am going to see if they can help me with this.


  1. Page RL, O’Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure: A scientific statement from the American Heart Association. Circulation 2016;134:e32-e69.