Old Age and ACE Inhibitors in Heart Failure: Cohort Study Tries to Bridge Guidelines Gap

June 01, 2018

VIENNA — Older age by itself should not decide whether a person with heart failure (HF) and reduced ejection fraction (EF) is prescribed angiotensin-converting enzyme (ACE) inhibitors  or angiotensin-receptor blockers (ARBs), suggests a cohort study that attempts to fill in a gap in the randomized-trial evidence base.

Such patients older than 80 years showed about the same relative-risk reductions for death and for death or HF hospitalization on those agents as did younger patients in a propensity-matched analysis based on the Swedish Heart Failure Registry (SwedeHF).

The older patients, inherently at greater mortality risk than the younger patients, showed steeper absolute risk reductions for those endpoints in the analysis, said Gianluigi Savarese, MD, PhD, Karolinska Institutet, Stockholm, Sweden, here at European Society of Cardiology Heart Failure (ESC-HF) 2018.

In his presentation of the study, Savarese noted that patients older than 80 make up about a fifth of the HF population. ACE inhibitors have a class 1A recommendation, but the major clinical trials supporting their use excluded patients in that age group.

As patients with cardiovascular disease live longer than ever, it's common now to see people older than 80 with HF, observed Christopher M. O'Connor, MD, from the Inova Heart & Vascular Institute, Falls Church, Virginia. 

"They're more mobile and active," he told theheart.org | Medscape Cardiology, "but we've excluded them from clinical trials." It's probably necessary now to raise the upper age limit in clinical trials to perhaps 90 years, or even do away with a ceiling, he said.

As the current analysis confirms, said O'Connor, "There's no reason to believe that there's some cliff based on age, that a drug works right up to age 79 and then doesn't work."

Also noting changes in HF patient demographics, session co-moderator Frank Ruschitzka, MD, University Heart Center, Zurich, Switzerland, said after the presentation, "I have a lot of 90-year-old patients now who look like 65. So the battle lines are shifting."

With prescribed medical therapy less than optimal in the very elderly with HF, the current findings "are broadly reassuring but also worrying to me," Wilfried Mullens, MD, PhD, Ziekenhuis Oost-Limburg, Genk, Belgium, said as an invited discussant for the analysis.

"Reassuring that the therapies still provide benefit even in the elderly population, and an even greater benefit compared to the younger patients, because the absolute risk of dying or hospitalization if you are elderly is extremely high."

But clinicians "fail to give these patients enough of these drugs," he said. "It's worrying that we don't do that."

O'Connor said the current analysis may help alleviate some of the nuanced language in the guidelines about who with HF should get ACE inhibitors. In practice, he said, lots of octogenarians with HF are prescribed the drugs anyway.

The current analysis should reinforce the practice, he said, and it "will probably encourage more use of these therapies in the elderly, which is a good thing."

The Swede-HF analysis was based on 6710 patients with HF and a left ventricular EF less than 40% who were older than 80 years; about 80% of the cohort were receiving ACE inhibitors or ARBs at baseline.

Savarese acknowledged that some patients likely stopped taking or initiated the drugs after baseline, a limitation of the analysis.

Comparison of those prescribed or not given the drugs showed many significant differences, as expected. Those taking them were less likely to be in NYHA class III or IV or to have had HF for more than 6 months, they had better renal function and were more likely to be receiving a β-blocker and less likely to be receiving diuretics, and they were more likely to be followed at an outpatient HF nurse-led clinic (P < .001 for all differences).

Propensity matching based on such baseline features yielded comparator groups of 1208 patients prescribed ACE inhibitors or ARBs and 1208 not taking them.

Table. Hazard Ratios for Outcomes in Patients With Systolic HF, ACE Inhibitors vs No ACE Inhibitors, by Age Group

Endpoints Hazard Ratio (95% CI)
Age >80 y Age ≤80 y
All-cause mortality 0.78 (0.72 - 0.86); NNT = 9 0.81 (0.71 - 0.91);NNT = 17
All-cause mortality or HF hospitalization 0.86 (0.79 - 0.94); NNT = 12 0.85 (0.76 - 0.94);NNT = 14
NNT = number needed to treat to prevent 1 endpoint.


Mullens listed what he sees as challenges in getting clinicians, at least in Europe, to prescribe ACE inhibitors more often to the older-than-80 age group. "First of all these elderly patients are often being taken care of by geriatricians and general physicians, who often lack the resources and the knowledge to take care of these difficult problems."

Second, such patients are typically taking multiple medications, he observed. "Often they will ask us to reduce their medications. What's happening in our institution, is when they are hospitalized in the geriatric wards, they cut down on their renin-angiotensin-system inhibition, again promoting further decompensation."

Finally, the very elderly tend to have comorbidities, often including renal dysfunction, Mullens said. "It's important for us, as heart failure physicians, to actually promote these drugs even if patients have bad kidney function, because these are the only drugs that can preserve and elevate glomerular function."

He called it "our duty" to teach geriatricians in the field that ACE inhibitors benefit these very elderly patients. "And I hope that this will actually break the clinical inertia that we're facing with these kinds of therapies."

Savarese discloses receiving research grants from Boehringer-Ingelheim and Merck. O'Connor discloses consulting fees from Novella and Amgen; ownership or partnership or being a principal in BisCardia; and research support from Otsuka, Roche Diagnostics, BG Medicine, Critical Diagnostics, Astellas, Gilead, GE Healthcare, and ResMed. Ruschitzka discloses receiving research grants from St Jude Medical and Novartis; personal fees for lectures from St Jude Medical, Servier, Zoll, Novartis, Bayer, and Abbott; and personal fees for advisory board or steering committee clinical trial meetings from AstraZeneca, Sanofi, Cardiorentis, Amgen, BMS, Pfizer, Fresenius, Vifor, and Roche. Mullens has recently disclosed that he has no relevant conflicts.

European Society of Cardiology Heart Failure (ESC-HF) 2018. Late breaking trial II - chronic heart failure; presented May 27, 2018.

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