Heart Failure Med Undertreatment Due to Older Age Common, Flouts Evidence

July 06, 2021

Advanced age by itself can be a reason physicians hold back on prescribing mainstay medications, or not uptitrate them per guidelines, to their older patients with heart failure (HF) and reduced ejection fraction (HFrEF), suggests a large cohort study.

About 80% of patients aged 80 years or older were prescribed renin-angiotensin-system inhibitors (RASi) in a multivariate-adjusted analysis of more than 27,000 patients in the Swedish Heart Failure Registry (SwedeHF). In contrast, such drugs — which included angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin receptor blockers, and ACE inhibitors — were prescribed to 95% of patients younger than 70 years.

Similarly, fewer of the oldest patients were offered meds from the two other drug classes core to HF management at the time, beta blockers and mineralocorticoid receptor antagonists (MRA).

And among those in the 80-and-older age group who were prescribed RASi or beta blockers, their uptitration more often fell short of even half the target dosage, compared with the youngest patients in the analysis.

Physicians may hold back on full guideline-directed medical therapy in their very elderly patients with HFrEF for many reasons, including a perceived likelihood of drug intolerance due to frailty or multiple comorbidities, including renal dysfunction, Davide Stolfo, MD, Karolinska Institutet, Stockholm, Sweden, and University of Trieste, Italy, told theheart.org | Medscape Cardiology.

But the current analysis was adjusted for about 80 variables "that in our interpretation may be main reasons for not introducing drugs and using them in the older patients," he said. They included care setting (that is, inpatient or outpatient), HF severity by several measures, a range of comorbidities, renal dysfunction, and history of serious illness such as cancer.

Even then, age emerged as a significant, independent predictor of medical therapy underuse in the oldest patients. Some physicians apparently see advanced age, by itself, as an "intrinsic reason" not to abide by HFrEF medical therapy recommendations, said Stolfo, who presented the analysis last week at HFA 2021, the annual meeting of the Heart Failure Association of the European Society of Cardiology (ESC-HFA), conducted both virtually and live in Florence, Italy.

Most major HF-drug trials have excluded or admitted few patients aged 80 years or older, but "the guidelines recommend treatment regardless of age, and in the trials there has been no influence from age on the effectiveness of drugs," Stolfo observed.

Moreover, in a prior SwedeHF analysis with propensity matching, patients with HFrEF aged 80 or older showed steeper reductions in risk for death or HF hospitalization from treatment with RASi than those in younger age groups.

One of the few randomized trials to focus on the very elderly, called SENIORS, enrolled patients aged 70 years and older — the average age was 76 — and saw a significantly reduced risk of death or cardiovascular hospitalization for those assigned to the beta blocker nebivolol. The benefits in the trial, which was conducted 15 years ago, were independent of left ventricular function.

So in the oldest patients, "we could question the need to achieve full dose of an evidence-based drug, but we shouldn't question the use of these drugs."

Table 1. Percentage Use of Drug Classes by Age Strata, HFrEF in Swedish Heart Failure Registry
Drug Class Total
(N = 27,430)
Age < 70 y
(n = 8515)
Age 70-79 y
(n = 9392)
> 80 y
(n = 9523)
RASi or ARNi (%) 88 95 90 80
Beta Blockers (%) 92 95 93 88
MRA (%) 45 54 47 35

The findings are consistent with a need to individualize medical therapy in senior patients with HFrEF, especially those of more advanced age, some of whom may be robust enough to be managed similarly to younger patients while others who may be less suitable for full guideline-directed medical therapy, Stolfo said.

Even for those who are more frail or have major comorbidities, drug therapy of HFrEF continues to be important for symptom control even if competing causes of death make it harder to prolong survival, Stolfo said.

"We should provide to all patients the best strategy they can tolerate," he said. "If we cannot greatly impact on the long-term survival for these patients, treatment can be aimed to improve the quality of life and keep the patient out of the hospital."

Table 2. Percentage Use of Multiple Drug Classes, Titration to < 50% by Age Strata, HFrEF in Swedish Heart Failure Registry
Parameter Total
(N = 27,430)
Age < 70 y
(n = 8515)
Age 70-79 y
(n = 9392)
> 80 y
(n = 9523)
% on all (RASi or ARNi) + beta blocker + MRA 38.9 50.1 41.6 26.1
% on 0 or only 1 of the 3 drug classes 10.8 5.9 9.6 20.5
% titrated to < 50% of beta blocker target dosage 29.4 21.3 27.2 39.6
% titrated to < 50% of RASi-ARNi target dosage 28.3 19.2 27.1 39.2

The analysis was supported by Boehringer Ingelheim. Stolfo disclosed personal fees from Novartis, Merck, GlaxoSmithKline, and Acceleron.

Heart Failure Association of the European Society of Cardiology (ESC-HFA) 2021: Chronic Heart Failure—Treatment 2. Presented June 29, 2021.

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