Elsevier

International Journal of Cardiology

Volume 386, 1 September 2023, Pages 59-64
International Journal of Cardiology

Hypotension at heart failure discharge: Should it be a limiting factor for drug titration?

https://doi.org/10.1016/j.ijcard.2023.05.007Get rights and content

Highlights

  • Hypotensive patients were traditionally excluded from pivotal trials in HFrEF.

  • Quadruple neurohormonal blockade titration is usually limited by low blood pressure.

  • This is a real-life HFrEF cohort where the intensity of treatment vs blood pressure is analysed.

  • Intensify treatment to maximum tolerated dose reduces mortality and hospitalizations.

  • Intensify treatment despite systolic blood pressure < 100 mmHg reduces mortality by 30%.

Abstract

Background

Medical treatment in Heart Failure (HF) with reduced ejection fraction (HFrEF; LVEF ≤40%) has shifted towards quadruple therapy. Maximum tolerated dose is the goal, yet no hypotension's cut-off point has been specified. In this work, we analyze the impact of intensive drug titration in clinical events, focusing on low blood pressure (BP) patients at hospital discharge.

Methods and results

Retrospective analysis of 713 patients with HFrEF discharged after an acute HF event (mean LVEF 30 ± 5%). Mean SBP was 112.4 ± 16.5 mmHg and 50.6% were discharged on triple therapy. We considered hypotension as a Systolic blood pressure (SBP) <100 mmHg (21.7% of patients, mean SBP was 112.4 ± 16.5 mmHg) and codified the intensity of drug therapy in 5 stages from untreated to very high therapy intensity. The impact of the intensity of treatment was analysed with a propensity score and increasing the intensity was associated in the whole cohort with a reduction of the composite outcome of all-cause mortality and HF readmission, (HR 0.69; CI95% 0.57–0.85, p < 0.001) and benefit in mortality was maintained for SBP < 100 mmHg (HR 0.42; CI95% 0.22–0.82; p = 0.011). Moreover, therapy intensity was clearly associated with lower risk of HF-hospitalization and death after the additional regression, considering SBP as a covariate, in the whole cohort (HR 0.70; CI95% 0.57–0.85; p < 0.001).

Conclusions

In this retrospective cohort analysis, patients with HFrEF and an acute-HF admission, intensive drug dose titration was related to better outcomes, even in patients with low blood pressure at hospital discharge. Therefore, hypotension is not a contraindication for NHB uptitration.

Introduction

Heart Failure (HF) is a major global health problem with significant morbidity and mortality. HF prevalence is 2.6% of individuals aged 45 or older and HF with reduced ejection fraction (HFrEF, EF ≤ 40% [1]) represent 52.4% of this figure [2]. HFrEF is a complex syndrome in which 4 drugs are the basis of the foundational therapy to modify/improve its long-term prognosis [1,3,4]: 1) Angiotensin-converting enzyme inhibitors (ACEi), Angiotensin II receptor blockers (ARB), or preferably angiotensin receptor–neprilysin inhibitors (ARNi), 2) Beta-blockers (BB), 3) Mineralocorticoid receptor antagonists (MRA), and 4) Sodium glucose cotransporter 2 inhibitors (SGLT2i).

Hypotension and hyperkalemia are the most frequent reasons for treatment discontinuation or up-titration failure [5,6] and low blood pressure is the most common reason for discharge on lower dose or no ACEi/ARB/BB, [[7], [8], [9], [10]] although suboptimal target doses have been also reported among patients with normal blood pressure (BP) [11]. While high BP increase cardiovascular events in the follow-up [12,13], low BP has also been related with tissue hypoperfusion and worse prognosis [[14], [15], [16]]. In fact, low blood pressure at hospital admission is a strong predictor of in-hospital mortality in HF [11,[17], [18], [19]]. Whether current practice guidelines recommend drug initiation and titration without cutoffs for blood pressure, thus suggesting it should be adapted to each patient considering their tolerance to blood pressure levels, the evidence of this based on pivotal trials is scarce, as patients with SBP under 90 mmHg or (more commonly) under 100 mmHg were excluded [20,21].

For this reason, it could be considered that the current recommendations for up-titrating HF medicines and the management of low BP in HF patients are weak [6,22]. Those toolkits require defining more precisely algorithms based on evidence medicine, since HF specialists need to know whether the aggressive up-titration management must be handled despite excessive BP control [23].

Our objective was to determine if high intensity medical treatment decreases hospitalizations due to HF and mortality even when patients are discharged with low blood pressure.

Section snippets

Patient population

Retrospective observational cohort study which included all consecutive patients with a diagnosis of HFrEF, discharged from the specialized heart failure unit of the Cardiology Department of the Complexo Hospitalario Universitario de Vigo (Vigo, Spain) between January 2010 and December 2020 (CardioCHUVI-IC registry).

Follow-up

The ascertainment of HF related events and death during follow-up was carried out until December 2021. Due to the assumption that therapy at discharge may be modified later in the

Patient characteristics

907 patients with HFrEF were found. After removal of missing and incomplete records, 713 patients were followed-up during a median-time of 3.58 years (interquartile range 1.60–6.21 years). Most of the patients were male with a mean age of 69 years-old, being 45.3% of them older than 75 years-old. LVEF was low, with a mean of 30 ± 5%, and they had CKD in 16.5% of cases. Mean SBP at discharge was 112.4 ± 16.5 mmHg (21.7% with SBP < 100 mmHg), and 50.6% were discharged on triple therapy: 81.9% on

Discussion

The present study is intended to analyze whether highly intensive treatment despite low SBP after the acute phase of HF is superior to a more conservative approach with less aggressive dosing titration of neurohormonal blockade.

In this real life cohort of patients with HFrEF, followed by HF specialists, our main findings were as follows: (1) Increasing NHB was clearly related to a reduction of 31% in the main composite outcome (death of all cause or HF readmission) in the whole cohort, even in

Ethics

This study complies with the Declaration of Helsinki. Hospital Alvaro Cunqueiro ethics committee has approved the research protocol (CardioCHUVI-IC). Finally, informed consent has been obtained from the subjects or their guardians.

Funding

No funding.

Disclosures

No relevant relationships with industry.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

None.

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  • Authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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