Preference and practice of Indian physicians towards the use of vasodilator di-hydralazine in the management of resistant hypertension
Keywords:RH, Di-hydralazine, Hydrazinophthalazine, Physician survey
Background: The treatment modalities of resistant hypertension (RH) remain a clinical challenge, often requiring secondary/add-on drugs with first-line therapy to control blood pressure (BP). This study was conducted to explore and understand the preferences and practices of Indian physicians towards the use of vasodilator (especially di-hydralazine) in the management of RH.
Methods: This was a cross-sectional, observational, web-based physician survey. The study included cardiologist, nephrologist and consultant physicians from different geographical regions of India. A web-based physician survey questionnaire (PSQ) was created in google forms and the link was circulated to the physicians. Responses obtained were analysed.
Results: A total of 457 physicians participated in this survey. In majority of the physicians, vasodilators were the treatment choice as secondary or add-on drugs with first line therapy to control BP in RH; especially hydralazine/di-hydralazine preferred the most. Majority of the physicians preferred to combine vasodilator with beta blocker and diuretic in patients with uncontrolled and RH. Cardiac failure, followed by chronic kidney disease (CKD), diabetes, dyslipidaemia, hypertensive emergency and angina were the common patient profile in RH in which majority physicians prescribed vasodilator (di-hydralazine). Majority of the physicians rated vasodilator di-hydralazine as “good-very good” in terms of efficacy, safety, tolerability, patient compliance and patient satisfaction in RH.
Conclusions: Overall, vasodilators (hydrazinophthalazine derivatives) are preferred as add-on drugs along with first-line drugs in RH. Physician’s opinion towards the use of di-hydralazine was positive. Di-hydralazine may be preferred as an add-on therapeutic option to control BP in RH, however randomized clinical trials are needed for recommendation in cardio-renal medicine.
Carey RM, Colhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR et al. Resistant hypertension: detection, evaluation and management: a scientific statement form the American Heart Association. Hypertension. 2018;72:e53-90.
Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;15;380(9859):2224-60.
Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365(9455):217-23.
Anchala R, Kannuri NK, Pant H, Khan H, Franco OH, Angelantonio E, et al. Hypertension in India: a systematic review and meta-analysis of prevalence, awareness, and control of hypertension. J Hypertens. 2014;32:1170-7.
Gupta R, Sharma KK, Soni S, Gupta N, Khedar RS. Resistant Hypertension in Clinical Practice in India: Jaipur Heart Watch. J Assoc Physicians Ind. 2019;67:14-7.
Bharatia RK, Chitale M, Saxena GN, Kumar RG, Chikkalingaiah, Trailokya A et al. Management practices in patients with uncontrolled hypertension. J Assoc Physicians Ind. 2016;64:14-21.
Zeisberg EM, Zeisberg M. A Rationale for Epigenetic Repurposing of Hydralazine in Chronic Heart and Kidney Failure. J Clin Epigenet. 2016;2:1.
Herman LL, Tivakaran VS. Hydralazine. In: StatPearls. Treasure Island (FL): Stat Pearls Publishing; 2020.
Mc Comb MN, Chao JY, Ng TM. Direct Vasodilators and Sympatholytic Agents. J Cardiovasc Pharmacol Ther. 2016;21(1):3-19.
Jacobs M. Mechanism of action of hydralazine on vascular smooth-muscle. Biochem Pharmacol. 1984;33(18):2915-9.
Ablad B. Site of action of hydralazine and dihydralazine in man. Acta Pharmacol Toxicol (Copenh) 1959;16:113-28.
Wilkinson EL, Backman H, Hecht HH. Cardiovascular and renal adjustments to a hypotensive agent (l'hydrazinophthalazine: Ciba BA-5968: apresoline) J Clin Invest. 1952;31:872-9.
Druey J, Marxer A. Hypotensive hydrazinophthalazines and related compounds. J Med Pharm Chem. 1959;1:1-21.
Rey E, Le Lorier J, Burgess E, Lange IR, Leduc L. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ. 1997;157:1245-54.
Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183:S1-22.
Brown MA, Hague WM, Higgins J, Lowe S, Mc Cowan L, Oats J et al. The detection, investigation and management of hypertension in pregnancy: executive summary. Aust N Z J Obstet Gynaecol. 2000;40:133-8.
Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327(7421):955-60.
ACOG Committee Opinion No. 767: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. Obstet Gynecol. 2019;133(2):e174-e80.
Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986;314(24):1547-52.
Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F et al. A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991;325(5):303-10.
Elkayam U, Bitar F. Effects of nitrates and hydralazine in heart failure: clinical evidence before the african american heart failure trial. Am J Cardiol. 2005;96(7B):37i-43.
Ziesche S, Cobb FR, Cohn JN, Johnson G, Tristani F. Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation. 1993;87(6):VI56-64.
Ku E, Lee BJ, Wei J, Weir MR. Hypertension in CKD: Core Curriculum 2019. Am J Kidney Dis. 2019;74(1):120-31.
Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int Suppl. 2012;2(5):337-414.
Wilkinson EL, Backman H, Hecht HH. Cardiovascular and renal adjustments to a hypotensive agent (l'hydrazinophthalazine: Ciba BA-5968: apresoline). J Clin Invest. 1952;31(10):872-9.
Woods JW, Blythe WB, Huffines WD. Management of malignant hypertension complicated by renal insufficiency. A follow-up study. N Engl J Med. 1974;291(1):10-4.
Pierpont GL, Brown DC, Franciosa JA, Cohn JN. Effect of hydralazine on renal failure in patients with congestive heart failure. Circulation 1980;61(2):323-7.