Underuse and underdosing of HF medication in elderly HF patients
Age differences in contemporary treatment of patients with chronic heart failure and reduced ejection fraction
Literature - Veenis JF, Brunner-La Rocca H-P, Linssen GCM et al. - Eur Heart J 2019: DOI: 10.1177/2047487319835042Introduction and methods
The majority of heart failure (HF) populations consists of elderly patients, with ~80% >65 years and 40-50% ≥75 years [1,2]. Optimizing HF management remains more challenging in elderly HF patients because of the high prevalence of comorbidities in these patients [3]. To date, only small numbers of elderly patients have been included in randomized clinical trials (RCTs) investigating HF treatment [4], except for the SENIORS trial [5]. Although discussion is ongoing on optimal therapy in elderly HF patients, there are no European Society of Cardiology (ESC) recommended age-specific guidelines for HF therapy [1], and data in groups of patients with advanced age are limited.
This observational study (n=8351) therefore investigated age-related differences in HF treatment in HF patients with reduced (HFrEF) and mid-range ejection fraction (HFmrEF) in the CHECK-HF registry, reflecting actual practice-based HF care at outpatient clinics including large numbers of elderly patients. The CHECK-HF (Chronisch Hartfalen ESC – richtlijn Cardiologische praktijk Kwaliteitsproject HartFalen) registry was a large-scale cross-sectional registry of 34 Dutch HF clinics that enrolled 10.910 patients with chronic HF, diagnosed according to the 2012 ESC guidelines [1], based on symptoms and echo parameters, who were seen at the outpatient’s HF clinic (96%) or general cardiology outpatient clinic (4%) (enrollment 2013-2016). Participants in the CHECH-HF registry were classified as HFrEF (LVEF <50%, n=8360) or according to 2016 ESC HF guidelines [6] as HFmrEF (LVEF= 40-49%, n=1574). Further stratification was based on age (<60 years [13.9%], 60-74 years [36.0%], and ≥75 years [50.2%]). Mean age of HFrEF participants was 72.3±11.8 years and of HFmrEF patients 73.7±11.7 years.
Main results
Pharmacological therapy in HFrEF
- Compared to patients aged <60 and 60-74 years, patients ≥75 years were treated significantly less often with beta-blockers (84.5%, 81.5% and 78.6%, respectively), RAS-inhibitors (76.1% vs. 90.0% and 86.9%), MRAs (51.8% vs. 63.8% and 55.0%) and ivabradine (3.2% vs. 9.9% and 5.2%) therapy but received significantly more often diuretics (88.5% vs. 75.7% and 80.6%) (all P<0.01).
- Treatment with all three HF drugs (beta-blockers, RAS inhibitors, and MRAs) was observed in 47.8%, 38.7% and 29.6% of patients in the three age groups (<60 years, 60-74 years and ≥75 years, respectively). Two out of three drugs were given in 39.9%, 45.4% and 47.6%, one out of three in 10.2%, 14.0% and 19.5%, and none in 2.1%, 1.9% and 3.3%, in patients <60 years, 60-74 years and ≥75 years, respectively (P<0.001).
- In patients ≥75 years, contraindications or intolerance rates were significantly higher for beta-blockers (3.8% vs. 1.8% and 2.9%), RAS inhibitors (6.4% vs. 1.8% and 3.4%) and MRAs (6.2% vs. 2.2% and 3.8%), compared to those aged <60 years and 60-74 years, respectively (P<0.01).
- 25.4%, 17.7% and 11.0% of participants (<60 years, 60-74 years and ≥75 years, respectively) achieved ≥50% of the target dose of all three HF drugs (beta-blockers, RAS inhibitors, and MRA). 38.6%, 40.6% and 35.7% achieved ≥50% of the target dose of two out of three medications, and 27.1%, 32.2% and 28.3% did not achieve ≥50% of the target dose of any medication.
- After adjustment for age, gender, NYHA classification and LVEF, the probability of treatment with beta-blockers, RAS inhibitor, MRA and ivabradine decreases for each 10-year increase in age by 12% (OR: 0.88, 95%CI: 0.83-0.92, P<0.01), 29% (OR: 0.71, 95%CI: 0.67-0.75, P<0.01), 10% (OR: 0.90, 95%CI: 0.86-0.93, P<0.01), and 31% (OR: 0.69, 95%CI: 0.64-1.39, P<0.01), respectively, whereas the probability of receiving diuretics increases by 32% (OR: 1.32, 95%CI: 1.26-1.39, P<0.01).
Device implantation in HFrEF
- Significantly more pacemakers (12.9% vs. 1.1% and 3.9%), but fewer implantable cardioverter defibrillator (ICD: 21.8% vs. 45.9% and 44.7%) and cardiac resynchronisation therapy (CRT: 16.5% vs. 17.3% and 21.8%) devices were received by elderly patients, compared to subjects aged <60 and 60-74 years, respectively.
- After adjustment for age, gender, NYHA classification and LVEF, the chance of receiving an ICD or CRT device decreases by 39% (OR: 0.61, 95%CI: 0.57-0.65, P<0.01) and 17% (OR: 0.83, 95%CI: 0.78-0.88, P<0.01), respectively, for every 10-year increase in age.
General therapy in subgroups of HFmrEF
- Participants aged ≥75 years were less often treated with beta-blockers (74.7% vs. 82.3, P<0.01), RAS inhibitors (71.9% vs. 88.0%, P<0.01) and ivabradine (2.1% vs. 5.9, P=0.02), compared to patients <60 years, while MRAs (46.0% vs. 35.4%, P=0.02) and diuretics (86.6% vs. 55.4%, P<0.01) were prescribed more often.

Conclusion
This observational study of a large Dutch registry of a real-world outpatient HF population showed that elderly HFrEF and HFmrEF patients (aged ≥75 years) were treated less often with recommended types and dosages of HF medication, and received less often ICD and CRT device treatment. These data suggest that in elderly HF patients there is a need for optimization of medical treatment and further uptitration of dosages or reflection on policy and acceptation of lower age-adjusted target doses in elderly HF patients when they do not tolerate higher dosages.
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