Physicians' Academy for Cardiovascular Education

Worse survival when using lower than recommended doses of ACEi/ARBs or beta-blockers in heart failure

Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study

Literature - Ouwerkerk W, Voors AA, Anker SD, et al. - European Heart Journal 2017; published online ahead of print


Based on relevant randomized studies, ESC guidelines for the treatment of heart failure (HF) recommend up-titration to maximum tolerated doses of beta-blockers and ACE-inhibitors (ACEi) or ARBs, if ACEis are not tolerated [1,2]. However, in daily clinical practice, many patients do not achieve the recommended doses, due to various reasons including low blood pressure and/or heart rate (HR), renal dysfunction, and electrolyte disturbances, or due to inadequate prescription adherence [3,4].

The BIOSTAT-CHF [5] is a European project designed to determine profiles of HF patients who do or do not respond to recommended therapies. In current analysis, the predictors, reasons and clinical outcomes of patients who did not reach recommended treatment doses of ACEi/ARBs and beta-blockers, were evaluated.

For this purpose, data of more than 2.500 patients with new-onset or worsening HF were studied. The diagnosis was confirmed either by LVEF ≤40% or by BNP values >400 pg/ml and/or NT-proBNP plasma levels >2000 pg/ml. Further eligibility criteria were furosemide ≥40 mg/day or equivalent at the time of inclusion as well as either no previous treatment with ACEi/ARBs and beta-blockers or low-dose (≤50% of target) of these drugs at time of inclusion. ACEi/ARBs and beta-blockers were up-titrated within 3 months and only patients who reached the end of the 3 months up-titration period were included in this analysis.

Main results


In the BIOSTAT-CHF study, reaching less than 50% of the recommended dose of ACEi/ARBs and beta-blockers was associated with worse survival. Patients who did not reach the recommended ACEi/ARBs or beta-blocker doses because of intolerance had worse survival compared to patients who did not reach their therapeutic targets because of other reasons. These findings support the adherence with the ESC guidelines on HF therapy, according to which maximum tolerated doses of ACEi/ARBs and beta-blockers are recommended.


Show references

Find this article online at Eur heart J

Share this page with your colleagues and friends: