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ARNI use safe and effective in elderly HFrEF patients

Literature - Esteban-Fernández A, Díez-Villanueva P, Vicent L et al., - Rev Esp Geriatr Gerontol. 2019. https://doi.org/10.1016/j.regg.2019.10.002

Introduction and methods

Prevalence of HF increases with age [1-4]. However, in clinical HF trials elderly patients are underrepresented as the mean age lies below 65 years [5,6]. HF medication with impact on survival are less frequently used in the elderly population due to a lack of evidence, more adverse effects, higher prevalence of comorbidities and lower adherence [7-9]. The PARADIGM-HF study showed that Sacubitril/Valsartan (S/V) reduced the risk of CV mortality and HF hospitalization in symptomatic HFrEF patients [6]. A sub-analysis with patients over 65 years of age showed that this population also benefits from treatment with S/V with similar safety [10]. However, due to lower incidence of the primary outcome in elderly patients compared to other trials and restricted inclusion criteria in PARADIGM-HF, an evaluation of S/V in real-world cohort of elderly patients was desired.

This study performed a prospective registry of elderly HFrEF patients who started S/V in clinical practice in 10 hospitals of Madrid Autonomic Community. 427 Patients were enrolled, with a mean age of 68.1 ± 12.4 years. 222 (52.0%) Were <70 years of age, 140 (32.8%) were between 70 and 79 years and 65 (15.2%) were ≥80 years. The mean follow-up was 7.0 ± 0.1 months. Occurrence of events (death, emergency room visits and hospitalization), S/V adverse effects, clinical characteristics, and maximum tolerated dose and drug withdrawal were analyzed.

Main results

  • No differences in prevalence of adverse effects were observed in the three different age groups; <70 years, 70-79, and ≥80 (25.2%, 25.7%, 23.1% respectively; P=0.835). Among adverse effects, symptomatic hypotension was the most frequently reported.
  • Higher doses at the end of follow-up were achieved in younger patients. In the youngest age group 46.3% received 97/103 mg b.d. and 19.5% received the lowest dose of 24/26 mg b.d. In the oldest age group, only 16.9% achieved a dose of 97/103 mg b.d. at the end of follow-up, while 36.9% received a dose of 24/26 mg b.d..
  • The withdrawal rate of S/V decreased with increasing age group (14.4%, 10.0%, 4.6% respectively; p = 0.05) and was related to poor prognosis (HR 13.51, 95% CI 3.22–56.13, P< 0.001).
  • NYHA class improved with S/V use and NYHA class improvement increased with increasing age group (66.2%, 83.6% and 93.9%, respectively; P<0.01).

Conclusion

This prospective registry study of real-world data of elderly HFrEF patients who received S/V, suggests that S/V is safe and effective in elderly patients. No age-related differences were found in the prevalence of adverse events. More older patients (≥ 80 years) achieved a lower dose compared to younger patients (<70 years).

References

1. Bleumink GS, Knetsch AM, Sturkenboom MCJM, Straus SM, Hofman A, DeckersJW, et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J.2004;25:1614–9.

2. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart.2007;93:1137–46.

3. Bursi F, Weston SA, Redfield MM, et al. Systolic and diastolic heart failure in the community. JAMA. 2006;296:2209–16.

4. Anguita Sánchez M, Crespo Leiro MG, de Teresa Galván E, Jiménez Navarro M,Alonso-Pulpón L, Muniz García J, et al. Prevalence of heart failure in the Spanish general population aged over 45 years: the PRICE Study. Rev Esp Cardiol.2008;61:1041–9.

5. Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators. A randomizedtrial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.

6. McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al.Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med.2014;371:993–1004.

7. Garg P, Wijeysundera HC, Yun L, Cantor WJ4, Ko DT. Practice patterns and trendsin the use of medical therapy in patients undergoing percutaneous coronaryintervention in Ontario. J Am Heart Assoc. 2014;3, e000882.

8. Fernández Lisón LC, Barón Franco B, Vázquez Domínguez B, Urendes Haro JJ,Pujol de la Llave E. Medication errors and non-compliance in polymedicatedelderly patients. Farm Hosp. 2006;30:280–3.

9. Crespo-Leiro MG, Segovia-Cubero J, González-Costello J, Bayes-Genis A, López-Fernández S, Roig E, et al. Adherence to the ESC heart failure treatment guidelinesin Spain: ESC heart failure long-term registry. Rev Esp Cardiol (English Ed).2015;68:785–93.

10. Jhund PS, Fu M, Bayram E, Chen CH, Negrusz-Kawecka M, Rosenthal A, et al.Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insightsfrom PARADIGM-HF. Eur Heart J. 2015;36:2576–84.

Find this article online on Rev Esp Geriatr Gerontol.

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