Association between renin-angiotensin system inhibitor use and mortality/morbidity in elderly patients with heart failure with reduced ejection fraction: a prospective propensity score-matched cohort

//Presented at ESC Heart Failure 2018 in Vienna, Austria, by Gianluigi Savarese (Stockholm, Sweden) //

Introduction and methods

The Rotterdam Study, and others, have demonstrated the increasing evidence of heart failure (HF). Octogenerians constitute an important HF subpopulation, as HF increases with aging. While the incidence of HF in those aged 80-84 is 30.1 per 1000 patient-years (PY), in increases to 41.9 per 1000 PY in those 85-89 years old and even to 47.4 per 1000 PY in those of 90 years and older. Mortality is higher in those of 80 years and older, but the Euro HF Survey II has shown that the octogenarians receive less treatment.

The 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic HF, treatment with an ACE-inhibitor (ACEi) is recommended, in addition to a beta-blocker for symptomatic patients with HFrEF, to reduce the risk of HF hospitalization and death (class I, level A recommendation). In HFrEF trials, octogenarians are often neglected. A study by the ACEi Myocardial Infarction Collaborative Group checked for interactions of age-groups with the treatment effect of long-term ACEi therapy in patients with HF of left ventricular dysfunction. Patients of 75 years and older did not show a significant interaction with ACEi on all-cause death or MI or HF hospitalization (HFH). But, this was a small sample size.

The current study aimed to study the effect of RAS-inhibition (RASi) in patients with HFrEF (EF<40%) of at least 80 years old, using data of SwedeHF, a database of patients with clinician-judged HF.

Main results

• Of 6710 patients of over 80 years, 80% received RASi.
• When comparing RASi with no-RASi, patients on RASi had more follow-up in specialty care, had less severe HF, received more HF therapies, fewer comorbidities and a better social environment.
• Propensity-score matching was performed to make the propensity score distribution similar in RASi and no-RASi. 2416 patients were included in this analysis (1208 in each arm).
• RASi was associated with improved mortality/morbidity, with an HR of 0.78 (95%CI: 0.72-0.86, 1 year absolute risk reduction [ARR]: 11%, NNT: 9) for overall mortality, and HR: 0.86 (95%CI: 0.79-0.94, 1-year ARR: 8%, NNT: 12) for the composite of all-cause death and HFH.
• The risk reductions in those aged 80 years and older were similar to those in a control analysis in patients younger than 80 years, but the 1-year ARR was 6% (NNT:17) for overall mortality and 7% (NNT:14) for the composite outcome.
• Subgroup analyses showed a significant interaction for a history of ischemic heart disease, such that those with a history had greater benefit of treatment.

Conclusions

These data of SwedeHF show that in HFrEF patients of 80 years and older, RASi use was associated with improved mortality and morbidity. The relative risk associated with this treatment was similar to that seen in those under 80 years, but the absolute risk reduction is greater in the octogenarians than in younger patients.

Limitations of this analysis include that RASi use was defined at baseline, and no information is available about potential cross-over. Moreover, there may be unmeasured confounders, as in other observational studies. For the same reason, this study does not allow drawing causal conclusions. The generalizability of these results to other countries is unclear.

Discussion

Discussant W. Mullens (Genk, BE) applauded this well-conducted observational study in an important patient population. These patients are the ‘frequent flyers’, but we often fail to take good care of them. The Swedish registry is great to study treatment effects. Especially in the elderly, we know from EURO-HF that treatment is suboptimal. And RCTs are done in selected patient groups, so these insights are important.

He called these data reassuring and also worrying. Reassuring because now we can try to get this patient group take these drugs. Worrying because we haven’t done it thus far. How can we change this, how can we educate the people involved? Another challenge is that these patients are often polypharmacized. We should take our duty seriously to also teach the geriatrician community that elderly patients will benefit from RASi treatment.

What remains to be studied, is adverse events, as nothing in life is free. This study did not consider adverse events; they may explain why some patients did not take RASi yet.

Our reporting is based on the information provided at the ESC Heart Failure 2018 congress