Maximum tolerated medication dose and other predictors of mortality in heart failure with reduced ejection fraction:...

In real-world patients with Heart Failure with reduced Ejection Fraction (HFrEF), it is unclear whether up-titration of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) and beta-blockers to maximal tolerated dose is beneficial.

To assess whether achievement of maximal tolerated heart failure therapies confers increased prognostic benefits, as compared with use of submaximal doses.

Retrospective cohort study.

Ambulatory HFrEF patients from two outpatient clinics in Adelaide, South Australia.

Percentage of target dose of ACEi/ARB and beta-blocker, all-cause mortality.

Of 489 patients, with a mean age of 71 ± 14 years, 67% male, 304 (62%) died over a mean 4.0 years of follow-up. Increasing ACEi/ARB dose from 50 to 100% target dose was independently associated with improved survival (adjusted HR 0.74 [95% CI 0.63-0.87]). Similar improvement in mortality was seen with up-titration of beta-blockers (adjusted HR 0.79 [0.65-0.93]). Significant predictors associated with improved survival included younger age, systolic blood pressure in the range 100-120 mmHg, absence of comorbidities including chronic renal failure and peripheral vascular disease, and care by a multidisciplinary specialist clinic.

This study, whilst predating angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor use, confirms the importance of achieving maximal tolerated doses of ACEi/ARB and beta-blocker therapy, to maximise associated prognostic benefits in a real-world population. Our findings also highlight the need for continued focus on up-titration of these therapies in the ambulatory setting, and the benefits of a multidisciplinary approach.