Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure

Abstract

Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).OBJECTIVE To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. DESIGN, SETTING, AND PARTICIPANTSRandomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019.INTERVENTIONS Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. MAIN OUTCOMES AND MEASURESThe primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. RESULTS Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, −3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%).CONCLUSIONS AND RELEVANCE Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

Time‐sensitive approach in the management of acute heart failure

“…[62][63][64] Therefore, vasodilating agents should be used cautiously in normotensive patients with the risk of hypotension. 61,62,65 Furthermore, natriuretic peptide agents reduce the blood pressure more than nitrates, making them unsuitable as first-line vasodilators for normotensive patients with AHF. 32,62,65 Systemic congestion…”

“…Previous studies reported that early administration of vasodilators, even in the pre‐hospital setting, is associated with a lower morality risk in patients with pulmonary congestion 11,49,59 . Hence, recent clinical practice guidelines for HF have pragmatically recommended vasodilators as the first‐line medical therapy for patients presenting with pulmonary congestion, 7–9 despite no confirming evidence on their long‐term benefits associated with reduced mortality other than improved haemodynamics and dyspnoea 21,22,60,61 . However, hypotension may occur as an adverse effect of vasodilating agents and has been previously associated with unfavourable effects on morbidity and mortality, thereby limiting the beneficial vasodilatory effects 62–64 .…”

“…The latest large-scale AHF trial with vasodilators, including an AHF population who had overlapping symptoms with pulmonary and systemic congestion, failed to show favourable effects of the experimental drugs (such as ularitide and serelaxin) with early initiation and dose titration on patient outcomes. 21,22,61 Thus, in this heterogeneous phenotype, clinicians should identify unique populations to guide the administration of individual therapies with the early treatment strategy. However, based on previous studies, stratification according to systolic blood pressure and natriuretic peptide levels is not enough to identify the population who could benefit from early intervention.…”

Mechanisms of Diuretic Resistance Study: design and rationale

“…[3][4][5][6] Contrary to significant advances in medical therapies for the treatment of chronic heart failure (HF), recent clinical trials of new ADHF therapeutics and treatment strategies have been negative. [7][8][9][10][11][12][13] Thus, loop diuretics remain the predominant therapy to treat fluid and sodium retention in ADHF and will remain so for the foreseeable future.…”

A Review on Current Scenario of Oral Cancer in India With Special Emphasis on Modern Detection Systems and Biomarkers

“…Ever-increasing burden of cancer becomes a major public health concern worldwide, posing a high impact on world health. Mortality due to cancer now exceeds the deaths caused by coronary heart diseases or all strokes [1]. International Agency of Research on Cancer (IARC) estimated 14.1 million new cancer incidences and 8.2 million cancer deaths worldwide in its online database GLOBOCAN 2012.…”