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37.29 HFrEF pharmacological treatment: hydralazine and isosorbide dinitrate
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Published:July 2018
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Abstract
The use of hydralazine and isosorbide dinitrate in combination with renin–angiotensin blockade and evidence-based beta-blocker therapy is an accepted therapy for heart failure with reduced ejection fraction (HFrEF). However, differing assessments of the evidence base and the strength of recommendation are noted between the heart failure guideline writing committees in America and Europe, so much so that this may the largest digression of opinion between the two august groups. Three randomized clinical trials in the United States provide the cornerstone evidence for use of hydralazine and nitrates in selected patients with HFrEF. The explanation of the potential mechanism of action for combination hydralazine and nitrate therapy in certain HFrEF populations has shifted from a haemodynamic to a neurohormonal model based on better understanding of the role of nitric oxide and oxidative stress imbalances in the pathogenesis of HFrEF. The differing professional interpretations of the data and the unique cohort studied most avidly (i.e. those of African descent), have resulted in unusually low use of this regimen despite evident salutary benefits. Moreover, the available preparation requires thrice-daily dosing and important side effects limit its tolerability. The future of hydralazine and isosorbide dinitrate use in patients with HFrEF will be informed by ongoing research allowing for more precise alignment of treatment and response. Even more so, further research to explore how best to modulate nitric oxide in cardiovascular disease including the application of pharmacogenomics may expose new therapeutic directions in the treatment of heart failure.
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