Mohamed Farag1, Thato Mabote2, Ahmad Shoaib2, Jufen Zhang2, Ashraf F Nabhan3, Andrew L Clark2, John G Cleland4. 1. Department of Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull HU16 5JQ, UK. Electronic address: mohamedfarag@nhs.net. 2. Department of Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull HU16 5JQ, UK. 3. Postgraduate Medical School, Ain Shams University, Cairo, Egypt. 4. National Heart & Lung Institute, Imperial College, London, UK.
Abstract
BACKGROUND: Hydralazine (H) and nitrates (Ns), when combined, reduced morbidity and mortality in some trials of chronic heart failure (CHF). It is unclear whether either agent used alone provides similar benefits. We aimed to evaluate the effects of H and/or N in patients with CHF. METHODS: A systematic review of randomised trials assessing the effects of H and N in CHF. For meta-analysis, only the endpoints of all-cause mortality and cardiovascular mortality were considered. RESULTS: In seven trials evaluating H&N in 2626 patients, combination therapy reduced all-cause mortality (OR 0.72; 95% CI 0.55-0.95; p=0.02), and cardiovascular mortality (OR 0.75; 95% CI 0.57-0.99; p=0.04) compared to placebo. However, when compared to angiotensin converting enzyme inhibitors (ACEIs), combination therapy was associated with higher all-cause mortality (OR 1.35; 95% CI 1.03-1.76; p=0.03), and cardiovascular mortality (OR 1.37; 95% CI 1.04-1.81; p=0.03). For N alone, ten trials including 375 patients reported all-cause mortality and showed a trend to harm (13 deaths in those assigned to nitrates and 7 to placebo; OR 2.13; 95% CI 0.88-5.13; p=0.09). For H alone, three trials showed no difference in all-cause mortality compared to placebo (OR 0.96; 95% CI 0.37-2.47; p=0.93), and two trials suggested inferiority to ACEI (OR 2.28; 95% CI 1.03-5.04; p=0.04). CONCLUSIONS: Compared to placebo, H&N reduces mortality in patients with CHF. Whether race or background therapy influences benefit is uncertain, but on direct comparison H&N appears inferior to ACEI. There is little evidence to support the use of either drug alone in CHF.
BACKGROUND:Hydralazine (H) and nitrates (Ns), when combined, reduced morbidity and mortality in some trials of chronic heart failure (CHF). It is unclear whether either agent used alone provides similar benefits. We aimed to evaluate the effects of H and/or N in patients with CHF. METHODS: A systematic review of randomised trials assessing the effects of H and N in CHF. For meta-analysis, only the endpoints of all-cause mortality and cardiovascular mortality were considered. RESULTS: In seven trials evaluating H&N in 2626 patients, combination therapy reduced all-cause mortality (OR 0.72; 95% CI 0.55-0.95; p=0.02), and cardiovascular mortality (OR 0.75; 95% CI 0.57-0.99; p=0.04) compared to placebo. However, when compared to angiotensin converting enzyme inhibitors (ACEIs), combination therapy was associated with higher all-cause mortality (OR 1.35; 95% CI 1.03-1.76; p=0.03), and cardiovascular mortality (OR 1.37; 95% CI 1.04-1.81; p=0.03). For N alone, ten trials including 375 patients reported all-cause mortality and showed a trend to harm (13 deaths in those assigned to nitrates and 7 to placebo; OR 2.13; 95% CI 0.88-5.13; p=0.09). For H alone, three trials showed no difference in all-cause mortality compared to placebo (OR 0.96; 95% CI 0.37-2.47; p=0.93), and two trials suggested inferiority to ACEI (OR 2.28; 95% CI 1.03-5.04; p=0.04). CONCLUSIONS: Compared to placebo, H&N reduces mortality in patients with CHF. Whether race or background therapy influences benefit is uncertain, but on direct comparison H&N appears inferior to ACEI. There is little evidence to support the use of either drug alone in CHF.