Mini review: The clinical avenues of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction

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Asim Ahmed Elnour
Adel Sadeq
Azza Ramadan
Abdalla Alamoodi
Alin Alkawarit
Asma Faisal Alshammari
Israa Yousif Elkhidir
Nouf Eid Alrashidi
Parisa kouhgard
Mariam Mohamed Al Qahtani
Semira Abdi Beshir
Khalid Awad Al-Kubaisi
Nadia Al Mazrouei
Maisoun Alkaabi
Afaf Ashoor


hydralazine-nitrate; heart failure with reduced ejection fraction (HFrEF), hydralazine, isosorbide dinitarte, randomized clinical trials, Vasodilator Heart Failure Trial I (V-HeFT I), the Vasodilator Heart Failure Trial II (V-HeFT II), New York Heart Association (NYHA)


Background: Combined hydralazine-nitrate has an avenue in the management of subjects with heart failure with reduced ejection fraction. Exploring the pharmacotherapy in this context will facilitate the clinical utility of the combined therapy. Objective: The main objective of this mini-review was to evaluate the role of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction. Methods: We conducted a literature search on Google scholar, MEDLINE, and PubMed to identify the randomized clinical trials on combined hydralazine-nitrate, in subjects with heart failure with reduced ejection fraction. 2760 articles were returned initially out of which 10 trials were conforming to the inclusion criteria. However, three trails were the focus for the current mini-review. Key findings: The current mini-review lends support to the use of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction (HFrEF). The combination may offer subjects who have remained symptomatic with HFrEF despite optimum dosing of standard therapy. Black subjects with HFrEF have proved to benefit from combined hydralazine-nitrate. The combination (e.g. small dose of hydralazine 12.5-25 mg twice a day and isosorbide mononitrate 10 mg twice a day) may provide alternative clinical utility in subjects with contraindications (renal artery stenosis, creatinine clearance less than 30 mL/minute, sustained hyperkalemia) to the use of ACEinh, ARBs, and/or ARNI. Subjects with HFrEF on combined hydralazine-nitrate should be assessed and monitored for systolic BP (keep >120 mmHg) and subjects with chronic kidney disease (keep eGFR > 30 mL/min/1.73 m2). Hydralazine-nitrate was inferior to ACEinh (higher all-cause mortality and cardiovascular mortality. Conclusion: The current minireview provides the key points to support the use of hydralazine-nitrate in subjects with heart failure with reduced ejection fraction..

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