Evidence-based drug therapy in the management of heart failure

2000

Circulation, 2001

ESC Heart Failure, 2019

Aims Clinical trials of new heart failure (HF) therapies administer guideline-directed medical therapy (GDMT) as background pharmacologic treatment (BPT). In the ANTHEM-HF Pilot Study, addition of autonomic regulation therapy to GDMT significantly improved left ventricular function, New York Heart Association (NYHA) class, 6 min walk distance, and quality of life in patients with HF with reduced ejection fraction (HFrEF). A post hoc analysis was performed to compare BPT in ANTHEM-HF with two other trials of novel HF therapies: the PARADIGM-HF study of sacubitril-valsartan and the SHIFT study of ivadrabine. All three studies evaluated patients with HFrEF, and the recommendations for use of GDMT were similar. A left ventricular ejection fraction ≤40% was required for entry into ANTHEM-HF and PARADIGM-HF and ≤35% for SHIFT. NYHA 2 or 3 symptoms were required for entry into ANTHEM-HF, and patients with predominantly NYHA 2 or 3 symptoms were enrolled in PARADIGM-HF and SHIFT. Methods and results Data on BPT were obtained from peer-reviewed publications and the public domain. Pearson's χ 2 test was used to evaluate differences in proportions, and Student's unpaired t-test was used to evaluate differences in mean values. The minimum period of stable GDMT required before randomization was longer in ANTHEM-HF: 3 months vs. 1 month in PARADIGM-HF and SHIFT, respectively. When compared with PARADIGM-HF and SHIFT, more patients in ANTHEM-HF received beta-blockers (100% vs. 93% and 89%, P < 0.04 and P < 0.007) and mineralocorticoid receptor antagonists (75% vs. 55% and 61%, P < 0.002 and P < 0.03). More patients in PARADIGM-HF received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker than in ANTHEM-HF or SHIFT (100% vs. 85%, P < 0.0001, and 100% vs. 91%, P < 0.001), which was related to PARADIGM's design. When beta-blocker doses in ANTHEM-HF and SHIFT were compared, significantly fewer patients in ANTHEM-HF received doses ≥100% of target (10% vs. 23%, P < 0.02), and fewer patients tended to receive doses ≥50% of target (17% vs. 26%, P = 0.11). When ANTHEM-HF and PARADIGM-HF were compared, more patients in ANTHEM-HF tended to receive doses ≥100% of target (10% vs. 7%, P = 0.36), and fewer patients tended to receive doses ≥50% of target (17% vs. 20%, P = 0.56). Conclusions Background treatment with GDMT in ANTHEM-HF compared favourably with that in two other contemporary trials of new HF therapies. The minimum period of stable GDMT required before randomization was longer, and GDMT remained unchanged for the study's duration. These findings serve to further support the potential role of autonomic regulation therapy as an adjunct to GDMT for patients with HFrEF.

The Journal of Heart and Lung Transplantation, 2002

British Journal of Clinical Pharmacology, 2011

European Journal of Internal Medicine

Background: Knowledge on the association between heart failure (HF) etiologies, precipitant causes and clinical outcomes may help in ascertaining patient's risk and in selecting tailored therapeutic strategies. Methods: The prognostic value of both HF etiologies and precipitants for worsening HF were analyzed using the index cohort of BIOSTAT-CHF. The studied HF etiologies were: a) ischemic HF; b) dilated cardiomyopathy; c) hypertensive HF; d) valvular HF; and e) other/unknown. The precipitating factors for worsening HF were: a) atrial fibrillation; b) non-adherence; c) renal failure; d) acute coronary syndrome; e) hypertension; and f) Infection. The primary outcome was the composite of all-cause death or HF hospitalization. Results: Among 2465 patients included in the study, 45% (N = =1102) had ischemic HF, 23% (N = =563) dilated cardiomyopathy, 15% (N = =379) other/unknown, 10% (N = =237) hypertensive and 7% (N = =184) valvular HF. Patients with ischemic HF had the worst prognosis, whereas patients with dilated cardiomyopathy had the best prognosis. From the precipitating factors for worsening HF, renal failure was the one independently associated with worse prognosis (adjusted HR (95%CI) = =1.48 (1.04-2.09), p < 0.001). We found no interaction between HF etiologies and precipitating factors for worsening HF with regard to the study outcomes (p interaction > 0.10 for all). Treatment up-titration benefited patients regardless of their underlying etiology or precipitating cause (p interaction > 0.10 for all). Conclusions: In BIOSTAT-CHF, patients with HF of an ischemic etiology, and those with worsening HF precipitated by renal failure (irrespective of the underlying HF etiology), had the highest rates of death and HF hospitalization, but still benefited equally from treatment up-titration.

Journal of Cardiac Failure, 2008

Most common etiology of death on CPS was refractory cardiac dysfunction (41.3%) and with short-term survival was neurological/pulmonary dysfunction (53.6%). Six patients were bridged to LVAD. Conclusion: More than half of resuscitated patients weaned from CPS had LTS. Rapid initiation of CPS may permit long-term survival for some in-patients with cardiovascular collapse when initial advanced resuscitation fails. Strategies to improve end-organ function on CPS could lead to greater LTS.

Revista Portuguesa de Cardiologia, 2019

The PARADIGM-HF population may be very different from real-world heart failure patients'' Resposta à Carta ao Editor «A população do PARADIGM-HF pode ser muito diferente do mundo real dos doentes com insuficiência cardíaca» To the Editor: As highlighted by our analysis, 1 the epidemiological study in Lima 2 pertinently quoted by Walter Calderón, and another two large registries, 3,4 patients from randomized trials are frequently different from those found in our daily practice. However, the results of the PARADIGM-HF trial are changing and will continue to change the way we treat patients with heart failure and reduced ejection fraction. Recently, the TRANSITION trial demonstrated the safety of sacubitril/valsartan when initiated prior to discharge from hospitalization for heart failure, achieving similar titration rates (62% vs. 68%), 5 and PIONEER-HF showed that in-hospital initiation of sacubitril/valsartan further reduced NT-proBNP values (ratio of NT-proBNP at week 4 and 8 to baseline value: 0.53 vs. 0.75). 6 Concluding, different pieces of an intricate puzzle are coming together, contributing to the widespread adoption of neuromodulation in patients with heart failure and reduced ejection fraction.

European Journal of Heart Failure, 2013

This editorial refers to 'The epidemiology of heart failure, based on data for 2.1 million inhabitants in Sweden', by R. Zarrinkoub et al., published in this issue on pages 995 -1002.

Congestive Heart Failure, 2006