ABC | Volume 114, Nº3, March 2020

Statement Brazilian Position Statement on Resistant Hypertension – 2020 Arq Bras Cardiol. 2020; 114(3):576-596 Chart 1 – Classification of resistant hypertension Number of antihypertensive agents Controlled resistant hypertension N Uncontrolled resistant hypertension 6 5 4 3 Resistant hypertension 2 1 < 140/90 Blood pressure (mmHg) ≥ 140/90 Normotension Hypertension 1. Definition and Epidemiology Coordinator: Heitor Moreno Júnior. Authors: Juan Carlos Yugar-Toledo, Heitor Moreno Júnior, Miguel Gus, Guido Bernardo Aranha Rosito, and Luiz César Nazário Scala. 1.1. Definition/New Concepts Resistant hypertension (RHTN) is defined as blood pressure (BP) persistently above the recommended target values despite the use of three antihypertensive agents of different classes, including one blocker of the renin- angiotensin system (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]), one long- acting calcium channel blocker (CCB), and one long-acting thiazide diuretic (TZD) at maximum recommended and tolerated doses, administered with appropriate frequency and doses and with proven adherence. Other drugs may be added if the above ones fail (aldosterone antagonists, beta-blockers, and α -methyldopa). Experts disagree on issues related to dose/potency, although the main discussion occurs around the use of chlorthalidone or hydrochlorothiazide as the main TZD. 1 The definition above includes a subgroup of patients with RHTN whose BP is controlled with four or more antihypertensive medications, known as controlled RHTN (C-RHTN). 2,3 A proposal to classify the disease into C-RHTN and uncontrolled RHTN (UC-RHTN), 4 including refractory RHTN (Ref-RHTN), an extreme UC-RHTN phenotype involving use of five or more antihypertensive agents, 5 has gained space in the literature. 6,7 Thus, UC-RHTN is defined by BP levels that remain above the desired level (140/90 mmHg) despite the concomitant use of four or more antihypertensive agents of different classes and a fourth drug, which is generally a mineralocorticoid receptor antagonist or a central sympathetic inhibitor (Chart 1). 1.2. Control of Hypertension in Brazil and Worldwide An analysis of 135 population studies with 1 million individuals indicated that 31.1% of the adult population is hypertensive (95% CI; 30 to 32%), with an estimated rate of 28.5 and 31.5% in countries with the highest and lowest socioeconomic status, respectively. BP control varies according to socioeconomic status, reaching 28.4% in more developed countries and only 7.7% in those with a lower degree of development. 8 In Brazil, the control rate varied from 10.4 to 35.2% in populations studied in three regions of the country. 9 A study conducted in 291 centers in all five Brazilian regions including 2,810 patients evaluated the control rates of hypertension according to risk profile and target BP. For patients with lower risk and target levels < 140/90 mmHg, the control rate was 61.7%, while for those with high risk and target levels < 130/80 mmHg, the corresponding value was 41.8%. 10 1.3. Incidence and Prevalence of Resistant Hypertension The prevalence of RHTN among individuals with hypertension is estimated at 10 to 20% worldwide, resulting in approximately 200 million individuals with RHTN. 11 This variability is mainly due to differences in RHTN criteria and characteristics of the studied populations. The National Health and Nutrition Examination Survey (NHANES) reported a prevalence of RHTN of about 9% in individuals with hypertension, corresponding to 12.8% of the individuals using antihypertensive agents in the US. 12 Still, the actual prevalence of RHTN is unknown. A meta-analysis by Achelrod et al. 11 evaluating populations of individuals with treated hypertension found a prevalence of 13.72% (95% CI; 11.19 to 16.24%), according to 20 observational studies, and 16.32% (95% CI; 10.68 to 21.95%), according to four randomized controlled trials. 11 In Brazil, a multicenter study (ReHOT) including ambulatory BP monitoring (ABPM) showed a prevalence of RHTN of 11.7%. 13 Daugherty et al. 14 analyzed the incidence of RHTN in 205,750 patients with hypertension who initiated antihypertensive treatment between 2002 and 2006. The authors found a rate of 1.9% at 1.5 years of follow-up (0.7 per 100 patients per year), leading to a 1.47 higher cardiovascular (CV) risk at 3.8 years. 14 1.4. Factors Related to Resistant Hypertension RHTN is more prevalent in elderly, obese, and African descent individuals, as well as in patients with left ventricular hypertrophy (LVH), diabetes mellitus, chronic nephropathy, metabolic syndrome, increased alcohol and/or salt intake, and sedentary lifestyle. 1,15-17 Aspects related to RHTN include the following: 1) diagnostic factors – inadequate BP measurement technique, white-coat effect; 1,15 2) causal factors – increased salt sensitivity, volume expansion due to excessive salt intake or chronic kidney disease (CKD), use of nonsteroidal antiinflammatory drugs, anabolic steroids, oral contraceptives, sympathomimetic agents (nasal decongestants, appetite suppressants, cocaine), chemotherapeutic agents, antidepressants, erythropoietin, immunosuppressants, alcohol; 1,15 3) secondary causes of hypertension, including primary hyperaldosteronism, obstructive sleep apnea (OSA), CKD, renal artery stenosis, thyroid diseases; 15 4) therapeutic factors – medications that are either inappropriate or are used 580