Hydralazine and nitrates alone or combined for the management of chronic heart failure: A systematic review
Section snippets
Background
The therapy of chronic heart failure (CHF) has advanced dramatically over the last 20–30 years [1]. Good medical treatment with angiotensin converting enzyme inhibitors (ACEIs), beta adrenoceptor antagonists (BB) and mineralocorticoid receptor antagonists (MRAs), now approximately doubles life expectancy [2]. However, mortality rates remain high, particularly in the first year after a hospitalisation for heart failure [3]. ACEIs were initially thought to mediate their benefit, at least in part,
Methods
The study was designed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) Statement [7]. Inclusion criteria were as follows: randomised controlled trial comparing H or N, or a combination, versus placebo, or no therapy, or an active comparator, whether parallel or multiple arms (i.e. other arms with different class, route, and dosage) were used. The studies included were all for patients with CHF. Observational studies, studies in acute heart failure,
Hydralazine and nitrate combination
Seven studies of H&N combination were identified including 2626 patients [Table 1]. Four studies compared the combination to placebo, one study compared the combination to either placebo or captopril, and two studies compared the combination to enalapril. The majority of patients were men (58% AAOS) and had left ventricular systolic dysfunction (LVSD). The aetiology of heart failure was IHD in about 37% of patients. Common adverse effects reported in these trials are shown in Table 2.
Discussion
This is the first comprehensive systematic review and meta-analysis appraising the use of H or N, alone and in combination, for patients with CHF. It highlights the surprising lack of data on the effects of nitrates alone in heart failure despite their widespread use in clinical practice. The paucity of data on hydralazine is less surprising since this agent is rarely used. There is a substantial body of evidence to support the use of the combination of H+ISDN as an alternative to ACEI in the
Conclusions
H&N in combination confer a survival benefit in patients with CHF when compared to placebo, particularly in men, patients of AAOS, and with advanced heart failure due to LVSD. It is unclear whether background therapy has an important influence on observed benefit. Combination therapy may have a favourable effect on symptoms, exercise tolerance, ventricular function, and hospitalisation rate. There is little evidence to support the use of either H or N alone in CHF, although nitrates are
Statement of authorship
The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Contributors
MF and TM did the literature search. All the authors analysed the data, interpreted the findings, drafted the manuscript, and approved the manuscript submitted.
Authors' disclosures
None.
Funding
None.
Conflict of interest
None.
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2020, Journal for Nurse PractitionersCitation Excerpt :Farag et al15 concluded that ACEI are more effective at lowering all-cause mortality (P = .03) and cardiovascular mortality (95% P = .03) than hydralazine and nitrates combination. Nitrate therapy alone had no effect on all-cause mortality.15 While hydralazine therapy alone demonstrated a greater improvement in LVEF vs calcium channel blockers, it did not reduce all-cause mortality compared with placebo (P = .93).
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2017, Kidney InternationalCitation Excerpt :In this regard, hydralazine currently is undergoing clinical testing for cardiovascular efficacy and myocardial fibrosis in dialysis-dependent end-stage renal disease (ClinicalTrials.gov identifier: NCT02228408). In light of renewed interest in hydralazine for treatment of chronic heart failure (either in situations in which use of RAAS inhibitors is prohibited or as add-on therapy to existing RAAS-inhibitor regimens),34,35 it is attractive to speculate that low-dose hydralazine also may have similar efficacy in renoprotective regimens as in the heart.28,46,47 In summary, our studies show that low-dose hydralazine pre-empts AKI-to-CKD progression when treatment is initiated before ischemia-reperfusion injury (simulating the clinical situation of initiating treatment before surgical procedures in patients with a high risk of developing AKI).