Abstract
Background
Among patients with heart failure and reduced ejection fraction (HFrEF), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), β-blockers (BB) and mineralocorticoid receptor antagonist (MRA) are known as guideline-directed medical therapy to improve prognosis. However, low blood pressure (BP) and renal dysfunction are often challenges prevent clinical implementation, so we investigated the association of different combinations of GDMT treatments with all-cause mortality in HFrEF population with low BP and renal dysfunction.
Methods
This study initially included 51, 060 HF patients from the Swedish Heart Failure Registry, and finally 1464 HFrEF patients with low BP (systolic BP ≦ 100 mmHg) and renal dysfunction (estimated glomerular filtration rate (eGFR) ≦ 60 ml/min/1.73m2) were ultimately enrolled. Patients were receiving oral medication for HF at study enrollment, and divided into four groups (group 1–4: ACEI/ARB + BB + MRA, ACEI/ARB + BB, ACEI/ARB + MRA or ACEI/ARB only, and other). The outcome is time to all-cause mortality.
Results
Among the study patients, 485 (33.1%), 672 (45.9%), 109 (7.4%) and 198 (13.5%) patients were in group 1–4. Patients in group 1 were younger, had highest hemoglobin, and most with EF < 30%. During a median of 1.33 years follow-up, 937 (64%) patients died. After adjustment for age, gender, LVEF, eGFR, hemoglobin when compared with the group 1, the hazard ratio for all-cause mortality in group 2 was 1.04 (0.89–1.21) (p = 0.62), group 3 1.40 (1.09–1.79) (p = 0.009), and group 4 1.71 (1.39–2.09) (p < 0.001).
Conclusions
In real-world HFrEF patients with low BP and renal dysfunction, full medication of guideline-directed medical therapy is associated with improved survival. The benefit was larger close to the index date and decreased with follow-up time.
Graphic abstract
Similar content being viewed by others
References
Sayago-Silva I, García-López F, Segovia-Cubero J (2013) Epidemiology of heart failure in Spain over the last 20 years. Rev Esp Cardiol 66:649–656
Ferreira JP, Girerd N, Pellicori P et al (2016) Gault formulas for predicting cardiovascular mortality in population-based, cardiovascular risk, heart failure and post-myocardial infarction cohorts: the heart “OMics” in AGEing (HOMAGE) and the high-risk myocardial infarction database initiatives. BMC Med 14(1):181
Hillege HL, Girbes AR, de Kam PJ et al (2000) Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation 102:203–210
Damman K, Valente MA, Voors AA et al (2014) Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J 35:455–469
Ponikowski P, Voors AA, Anker SD et al (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 37:2129–2200
Greene SJ, Butler J, Albert NM et al (2018) Medical Therapy for heart failure with reduced ejection fraction. the CHAMP-Hf Registry. J Am Coll Cardiol 72:351–366
Parwani P, Ryan J (2012) Heart failure patients with low blood pressure: how should we manage neurohormonal blocking drugs? Circ Heart Fail 5(6):819
Jonsson A, Edner M, Alehagen U, Dahlstrom U (2010) Heart failure registry: a valuable tool for improving the management of patients with heart failure. Eur J Heart Fail 12:25–31
Stevens PE, Levin A, KDIGO Chronic Kidney Disease Guideline Development Work Group Members (2013) Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 158:825–830
Lee DS, Ghosh N, Floras JS et al (2009) Association of blood pressure at hospital discharge with mortality in patients diagnosed with heart failure. Circ Heart Fail 2:616–623
Royston P, Parmar MK (2002) Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects. Stat Med 21:2175–2197
Dewar R, Khan I (2015) A new SAS macro for flexible parametric survival modelling: applications to clinical trials and surveillance data. Comput Methods Programs Biomed 1:855–866
McAlister FA, Ezekowitz J, Tonelli M, Armstrong PW (2004) Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study. Circulation 109:1004–1009
Heywood JT, Fonarow GC, Costanzo MR et al (2007) High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail 13:422–430
Smith GL, Lichtman JH, Bracken MB et al (2006) Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol 47:1987–1996
Go AS, Yang J, Ackerson LM et al (2006) Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the anemia in chronic heart failure: outcomes and resource utilization (ANCHOR) study. Circulation 113:2713–2723
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351(13):1296–1305
Ahmed A, Kiefe CI, Allman RM, Sims RV, DeLong JF (2002) Survival benefits of angiotensin-converting enzyme inhibitors in older heart failure patients with perceived contraindications. J Am Geriatr Soc 50:1659–1666
Gheorghiade M, Abraham WT, Albert NM et al (2006) Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. JAMA 296:2217–2226
Tavazzi L, Maggioni AP, Lucci D et al (2006) Nationwide survey on acute heart failure in cardiology ward services in Italy. Eur Heart J 27:1207–1215
Ambrosy AP, Vaduganathan M, Mentz RJ et al (2013) Clinical profile and prognostic value of low systolic blood pressure in patients hospitalized for heart failure with reduced ejection fraction: insights from the efficacy of vasopressin antagonism in heart failure: outcome study with tolvaptan (EVEREST) trial. Am Heart J 165:216–225
Gheorghiade M, Vaduganathan M, Ambrosy A et al (2013) Current management and future directions for the treatment of patients hospitalized for heart failure with low blood pressure. Heart Fail Rev 18:107–122
Komajda M, Böhm M, Borer JS et al (2014) Efficacy and safety of ivabradine in patients with chronic systolic heart failure according to blood pressure level in SHIFT. Eur J Heart Fail 16:810–816
Böhm M, Young R, Jhund PS et al (2017) Systolic blood pressure, cardiovascular outcomes and efficacy and safety of sacubitril/valsartan (LCZ696) in patients with chronic heart failure and reduced ejection fraction: results from PARADIGM-HF. Eur Heart J 38:1132–1143
Metra M, Torp-Pedersen C, Swedberg K et al (2005) Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial. Eur Heart J 26:2259–2268
Funding
The Swedish Heart Failure Registry is funded by the Swedish Federal Government through the Swedish Association of local authorities and regions. No funding agency had any role in the design and conduct of the study, in the collection, management, analysis or interpretation of the data, or in the preparation, or approval of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
None.
Rights and permissions
About this article
Cite this article
Chen, X., Cui, X., Thunström, E. et al. Guideline-directed medical therapy in real-world heart failure patients with low blood pressure and renal dysfunction. Clin Res Cardiol 110, 1051–1062 (2021). https://doi.org/10.1007/s00392-020-01790-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00392-020-01790-y