ABC | Volume 115, Nº2, August 2020

Viewpoint Pharmacological Treatment of Hypertension: From the Golden Trio to the Octet Audes Diógenes Magalhães Feitosa, 1 Marco Mota-Gomes, 2 Oswaldo Passarelli Júnior, 3 Weimar Kunz Sebba Barroso , 4 R oberto Dischinger Miranda, 5 Eduardo Costa Duarte Barbosa, 6 A ndrea A. Brandão, 7 Wilson Nadruz 8 Unidade de Hipertensão e Cardiologia Preventiva, PROCAPE, Universidade de Pernambuco, 1 Recife, PE – Brazil Centro Universitário CESMAC, 2 Maceió, AL - Brazil Instituto Dante Pazzanese de Cardiologia, 3 São Paulo, SP – Brazil Universidade Federal de Goiás - Liga de Hipertensão, Goiânia, 4 GO - Brazil Universidade Federal de São Paulo - Escola Paulista de Medicina, 5 São Paulo, SP - Brazil Liga de Hipertensão de Porto Alegre, 6 Porto Alegre, RS – Brazil Universidade do Estado do Rio de Janeiro, 7 Rio de Janeiro, RJ - Brazil Universidade Estadual de Campinas, 8 Campinas, SP – Brazil The treatment of hypertension comprises numerous pharmacological options, which may hinder patient management standardization, thus contributing to therapeutic failure. 1 However, in more recent years, several studies and guidelines from diverse hypertension and cardiology societies have suggested preferential pharmacological classes to treat hypertension. 2-6 Based on this evidence, the present report aims to propose a simple and practical pharmacological treatment algorithm that can be applied to patients ranging from stage 1 to refractory hypertension cases (Figure 1). Hypertension treatment combines lifestyle changes (including salt intake reduction, weight control, physical activity performance , alcohol intake moderation, and smoking cessation), discontinuation of substances that may increase blood pressure (BP), and sequential addition of antihypertensive medications. 2-4,7,8 According to current hypertension guidelines, antihypertensive classes that should be preferentially initiated for the treatment of hypertensive patients include the so-called golden trio : 9 a renin-angiotensin system inhibitor (RASI) (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker), a calcium- channel blocker (CCB) or a thiazide-type/thiazide-like diuretic (THIAZ). 2-4 In most hypertensive patients, treatment initiation usually includes the combination of two pharmacological classes, an approach that aims to optimize BP control efficiency and predictability. Conversely, monotherapy has been recommended for stage 1 hypertensive patients with low cardiovascular risk, pre-hypertensive patients and frail elderly patients. 2,4 The usual preferred dual combinations comprise a RASI plus a CCB or a RASI plus a THIAZ, 4 although in patients with high cardiovascular risk the combination of RASI plus CCB seems to be superior to the combination of RASI plus THIAZ in reducing adverse cardiovascular events. 10 If BP control is not achieved with two pharmacological classes, the use of three drugs should be instituted, preferentially comprising the golden trio components. When these three drugs are used, but BP control is not achieved and hydrochlorothiazide is the prescribed THIAZ, this latter drug should be substituted by a long-acting THIAZ (chlortalidone or indapamide). 1,11 In addition, a loop diuretic, such as furosemide, should replace the THIAZ if glomerular filtration rate is <30 mL/min. 11 Beta-blockers ( β B), which were considered a preferential initial class for hypertension treatment in the past, 12,13 have not been recommended as a first-choice class to treat hypertension according to more recent guidelines. Therefore, β B have been indicated as monotherapy or in combination with other classes when there are specific indications, such as angina, post-myocardial infarction, heart failure, arrhythmia or heart rate control. 2-4 The inadequate control of BP with the use of three drug classes should be confirmed by ambulatory or home BP monitoring, after excluding causes of pseudo-resistant hypertension (mainly poor medication adherence and inadequate dosage). 1,11,14 Patients with uncontrolled BP using maximal dosages of three or more antihypertensive classes, including RASI, CCB and THIAZ, and in which pseudo- resistance was ruled out, are considered as having resistant hypertension, whereas those who have controlled BP while taking four antihypertensive classes, including RASI, CCB and THIAZ, are considered as having controlled resistant hypertension. Patients with uncontrolled BP using maximal dosages of five or more antihypertensive classes, including a long-acting THIAZ and spironolactone, are considered as having refractory hypertension. It is noteworthy that patients with resistant or refractory hypertension should undergo further investigation of end-organ damage and investigation/ treatment of secondary causes of hypertension. Growing evidence has suggested that, in the absence of BP control with optimized and concomitant use of RASI, CCB and THIAZ, the fourth antihypertensive class to be instituted should be an aldosterone antagonist, particularly low-dose spironolactone (25-50 mg/day), as demonstrated in several studies and meta-analyses. 5,15-17 However, spironolactone may not be tolerated by some patients, due to its anti-androgenic Mailing Address: Wilson Nadruz • UNICAMP - Cidade Universitária Zeferino Vaz. Postal Code 13083-872, Campinas, SP - Brazil E-mail: wilnj@fcm.unicamp.br Manuscript received November 06, 2019, revised manuscript January 22, 2020, accepted March 09, 2020 Keywords Hypertension; Antihypertensive Agents; Drug Therapy; Life Style; Exercise; Weight Loss; Medication Adherence. DOI: https://doi.org/10.36660/abc.20190780 270