Heart Failure with Reduced Left Ventricular Ejection Fraction in Patients Aged 70 Years or Older in Malta
: Epidemiology and Treatment Outcome of ACE Inhibitors and Angiotensin Receptor Blockers

  • Anthony Cutajar

Student thesis: Doctoral ThesisDoctor of Pharmacy


Approximately 80% of patients suffering from heart failure (HF) with reduced ejection fraction are elderly aged ≥70 years. Yet, patients aged over 70 years are under-represented in clinical trials that shaped current treatment. Results from large observational studies that followed are now used to extrapolate the same expected benefit on the present patient population. However, suitable representation of the real world remains problematic with longer survival and wider, multimodal treatment. This single-centre, retrospective research evaluated current and predicted burden of disease in the Maltese population and re-examined two key effectiveness aspects of renin angiotensin system (RAS) blockade with a focus on patients aged ≥70 years at incident diagnosis. First, are angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) effective at reducing all-cause mortality and HF hospitalisation? Second, are ARB effective as ACEI in this population? Incidence rates from 2007 to 2017 demonstrated fast rising trends of incident diagnosis accompanied by similar trends for related mortality with a sex gap where males fared worse. ACEI were prevalent in males while ARB were preferred in females. Treatment decreased with age and females experienced earlier treatment denial. Survival analysis revealed significant mortality reduction with ACEI and ARB that compared with younger patients, persisted for at least 3 years post incident diagnosis, and remained incremental with background treatment despite additional comorbidity. The sex disparity in preferential treatment was irrelevant because ARB were comparable to ACEI at reducing mortality. These findings were demonstrated by cohorts of patients aged ≥70 years at incident diagnosis. The influence of treatment on HF hospitalisation was heavily confounded by selection bias that precluded any conclusions. Nonetheless, if treatment is maintained the positive benefit of both RAS inhibitors of reduced mortality in elderly patients has a beneficial impact on the predicted disease burden that shall keep rising until 2040.
Date of AwardAug 2022
Original languageEnglish
SupervisorDavid Terry (Supervisor) & Chi Huynh (Supervisor)


  • Heart failure
  • elderly patients
  • ejection fraction
  • ACEI
  • ARB
  • hospitalisation
  • mortality
  • effectiveness

Cite this