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Causes and impact on survival of underuse of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in heart failure

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Abstract

Guidelines recommend angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) for treatment of heart failure with reduced ejection fraction (HFrEF), but these medications are underprescribed in clinical practice. We reviewed the records of HF patients receiving a first visit in a tertiary outpatient clinic from January 1st 2004 to May 31st 2015, and selected those with a serum creatinine concentration (sCr) available at both the first and last visit and < 3.5 mg/dL at baseline, and a left ventricular ejection fraction (LVEF) < 50% at the first visit. Of 570 eligible patients, 92 (16.1%) never received ACEi/ARB. Compared to ACEi/ARB users, never-users were older, more often women, had higher sCr and lower systolic blood pressure, were less commonly on beta-blocker, and had more frequently anemia. Current or prior cancer also tended to be more common in ACEi/ARB never-users. ACEi/ARB users displayed an improvement in LVEF by ≥ 10% of the baseline value more often than ACEi/ARB never-users (33.7% vs. 20.7%, respectively, P = 0.01), whereas no difference in percent variation of sCr levels was found between the two groups (8.2% vs. 3.1%, respectively; P = 0.13). Over a median follow-up of 56 months (range 1–137 months), 215 (37.7%) patients died. After multiple adjustments, ACEi/ARB never-use was associated with an almost twofold increased risk of all-cause mortality (HR 1.97, 95%CI 1.39–2.80). ACEi/ARB underuse in HFrEF is a standing issue with dramatic prognostic consequences. Efforts are needed to eliminate perceived contraindications to these drugs and ensure their implementation in real-life cardiology.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Genova, Genoa, Italy

    Edoardo Bertero, Roberta Miceli, Alessandra Lorenzoni, Manrico Balbi, Giorgio Ghigliotti, Claudio Brunelli, Francesca Viazzi, Roberto Pontremoli, Marco Canepa & Pietro Ameri

  2. Comprehensive Heart Failure Center, University Clinic Würzburg, Würzburg, Germany

    Edoardo Bertero

  3. Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Roberta Miceli, Alessandra Lorenzoni, Manrico Balbi, Giorgio Ghigliotti, Francesco Chiarella, Claudio Brunelli, Marco Canepa & Pietro Ameri

  4. Nephrology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Francesca Viazzi

  5. Internal Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Roberto Pontremoli

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  1. Edoardo Bertero
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Correspondence to Marco Canepa or Pietro Ameri.

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Bertero, E., Miceli, R., Lorenzoni, A. et al. Causes and impact on survival of underuse of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in heart failure. Intern Emerg Med 14, 1083–1090 (2019). https://doi.org/10.1007/s11739-019-02060-0

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