Polypharmacy Linked With Rehospitalization, Death Among Patients With HF

An analysis conducted in Japan among patients with acute decompensated heart failure (HF) revealed excessive polypharmacy at hospital discharge is associated with an increased risk of mortality after 1 year.

Polypharmacy at hospital discharge was common among Japanese patients with acute decompensated heart failure (ADHF) according to study findings published in the Journal of Cardiovascular Nursing, while excessive polypharmacy (≥ 12 medications) was associated with a higher risk of mortality and rehospitalizations within a 1-year period, authors found.

Polypharmacy and its subsequent risks are an increasing problem in contemporary clinical practice in patients with HF, researchers explained. Adverse drug reactions and a decline in medication adherence is of particular concern among older patients.

In those with HF and comorbidities, polypharmacy can pose additional risks. To better elucidate the impact of polypharmacy on clinical outcomes in ADHF patients, investigators evaluated medication use in real-world clinical practice via the Kyoto Congestive Heart Failure (KCHF) registry.

The physician-initiated, prospective, observational, multicenter cohort study enrolled patients with ADHF admitted to hospitals between 2014 and 2016; clinical follow-up data were collected in October 2017.

“The number of oral medications at the time of discharge from the index hospitalization was assessed by drug class according to the Anatomical Therapeutic Chemical Classification System. Therefore, a prescription of 2 types of loop diuretics in 1 patient was counted as 1 medication,” authors wrote.

A total of 2578 patients were included in the analysis, of whom 81.5% received a prescription of over 5 medications; 27.8% received more than 10 medications. The median number of medications received was 8 (IQR: 6-11) and patients were divided based on the number of medications taken at hospital discharge (quartile 1, ≤5; quartile 2, 6–8; quartile 3, 9–11; and quartile 4, ≥12).

Median patient age was 77 and the majority (60%) were male.

Analyses revealed:

  • Patients who received more medications had a greater BMI; more often had a history of HF admission, coronary artery disease, atrial fibrillation or flutter, diabetes, chronic kidney disease, anemia, and chronic lung disease; were more often unemployed; and more often used public assistance and long-term care insurance at hospital discharge than those who received fewer medications
  • No significant difference was found in the left ventricular ejection fraction, presence or absence of dementia, and living status according to the number of medications between these patients
  • Cumulative 1-year incidence of a composite of death or rehospitalization increased incrementally with an increasing number of medications (quartile 1, 30.8%; quartile 2, 31.6%; quartile 3, 39.7%; quartile 4, 50.3%; P < .0001)
  • After adjusting for confounders, the excess risks of quartile 4 relative to those of quartile 1 remained significant (P = .01)
  • The cumulative 1-year incidences of any rehospitalization and HF rehospitalization were also significantly higher in quartile 3 and quartile 4 than in quartile 1
  • The excess risk for HF rehospitalization per quartile of number of medications was also significant (HR, 1.18; 95% CI, 1.05–1.29; P = .0005).

However, the excess risk of a greater number of medications for 1-year incidence of death or rehospitalization was not significant in patients 80 years or older and patients with anemia, researchers noted, adding “unmeasured factors such as poor compliance may be accountable for this discrepancy.”

As populations around the world continue to live longer, the challenges of polypharmacy will follow suit, authors wrote. Approximately 9% of patients enrolled in the current study had dementia, while over 20% lived alone and 83% were unemployed. Previous research has shown dementia, social isolation, and unemployment are generally associated with poor medication adherence. However, programs like Japan’s long-term care insurance can help mitigate this challenge.

The study’s observational design raises the possibility of residual confounding and a lack of data on patient medication adherence and intake of over-the-counter drugs also mark limitations.

Overall, “cardiac rehabilitation and collaborative disease management programs that include the careful review of medication lists and an appropriate deprescribing protocol should be implemented for these patients,” researchers concluded.


Ozasa N, Kato T, Morimoto T, et al. Polypharmacy and clinical outcomes in hospitalized patients with acute decompensated heart failure. J Cardiovasc Nurs. Published online January 14, 2022. doi:10.1097/JCN.0000000000000885

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