Lack of evidence for intravenous vasodilators in ED patients with acute heart failure: a systematic review

Abstract

There are nearly 700,000 annual US emergency department (ED) visits for acute heart failure (AHF). While blood pressure is elevated on most of these visits, acute therapy remains focused on preload and not afterload reduction. Data from recent prospective studies suggest AHF patients with concomitant acute hypertension benefit from intravenous (IV) vasodilators. To better understand the use of vasodilators for such patients, we conducted a systematic review of 1) currently available intravenous vasodilators for ED patients with AHF, or 2) intravenous vasodilators which are not yet available, but have completed Phase III clinical trials in AHF, and may be available for ED use in the future. We employed multi-term search queries to retrieve research involving nitroglycerin, nitroprusside, enalaprilat, hydralazine, relaxin and nesiritide. A total of 2001 unique citations were identified from three databases: PubMed, EMBASE, and CINAHL. Of these, 1966 were excluded based on established review criteria, leaving 35 published papers for inclusion. Our primary finding was that IV nitrovasodilators, when used in the treatment of AHF in ED and ED-like settings, do improve short-term symptoms and appear safe to administer. There is no data suggesting they impact mortality. Other commonly used vasodilators such as hydralazine and enalaprilat have very little published data about their safety and efficacy. Of note, few studies enrolled patients early in their course of treatment. Thus, to assess the specific impact of vasodilator therapy on both short- and long-term outcomes, future research efforts should focus on patient recruitment in the ED setting.

Rate pressure product and the components of heart rate and systolic blood pressure in hospitalized heart failure patients with preserved ejection fraction: Insights from ASCEND‐HF

“…The landmark Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study included 404 patients with HFpEF and showed reduced rates of HFpEF in patients on chlorthalidone and a reduced risk for HF hospitalization . Although there are several studies demonstrating improvement in symptoms with blood‐pressure reduction in acute HF patients with HTN, the impact of blood‐pressure control in the acute setting on clinical outcomes and in the HFpEF population in particular has not been well studied …”

Efficacy and Safety of Intravenous Urapidil for Older Hypertensive Patients with Acute Heart Failure: A Multicenter Randomized Controlled Trial

“…Indeed, clinical evidence has also revealed the therapeutic role of vasodilators in hypertensive patients with AHF 919. However, these results generally come from observational studies, and evidence-based therapy in AHF is lacking 420. Indeed, although previous pilot trials, mostly from case reports or case series,1421 have suggested intravenous urapidil as a potential therapeutic option in patients with hypertension and AHF, randomized controlled trials are limited.…”

“…Moreover, there is increasing evidence that the prevalence of AHF is substantial in older adult patients complicated with hypertension, although evidence-based treatment strategies are generally lacking 4. The development of novel pharmacologic agents for patients with both hypertension and AHF is urgently needed.…”

Temporal trends in nitrate utilization for acute heart failure in elderly emergency patients: A single-centre observational study

“…Furthermore, some studies reported an absence of benefit in patients treated with nitrates [23,24], whereas others reported a significant improvement in terms of mortality and severe outcome after nitrate utilization [16,25]. A systematic review concluded that prescription of nitrates is based more on a clinical dogma than on high-quality trials, and reliable data on survival benefit are lacking [26]. Despite the absence of many high-quality, generalizable, randomized trials, evidence of benefit of a treatment strategy including nitrates in AHF has still been reported (in the ALARM-HF study), with the use of a powerful statistical tool to match patients [25].…”