Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC byDk6xBzmdw4vqkQCLXVKHx S0066-782X2016004800025 10.5935/abc.20160155 Diretrizes 7th Brazilian Guideline of Arterial Hypertension: Chapter 5 - Therapeutic Decision and Targets Malachias MVB Andrea Araujo Brandão AA Kaiser S Moreira O Filho 09 2016 107 3 Suppl 3 25 29 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction

The therapeutic management of elevated BP includes non-pharmacological measures and the use of antihypertensive drugs to reduce BP, protect target organs and prevent CV and renal outcomes.1-3 Non-pharmacological measures have proven efficient to reduce BP, although limited by medium- and long-term lack of adherence to treatment. A systematic review4 of studies with a minimum duration of 12-24 months, combining dietary interventions and moderate-to-high-intensity physical activity in patients using or not medications, has revealed a reduction in SBP and DBP for < 12 months of -4.47 (-7.91 to -1.04) mm Hg and -1.10 (-2.39 to 0.19) mm Hg, respectively. For 12 to 24 months, the reductions were -2.29 (-3.81 to -0.76) mm Hg and -1.00 (-3.22 to 1.22) mm Hg in SBP and DBP, respectively. The direct impact of those measures on the risk of CV outcomes is uncertain, the studies are small and short, and the effects on other RF could contribute to CV protection.

On the other hand, results of randomized placebo-controlled clinical trials on the use of antihypertensive drugs for hypertensive individuals have clearly shown a significant reduction in CV mortality, stroke, MI and HF. It is worth noting that most of those studies have assessed individuals aged ≥ 55 years, at high CV risk and for a follow-up period of 3 to 6 years, hindering, thus, the extrapolation of those benefits for long-term treatment and patients with other characteristics.

The therapeutic decision should be based not only on BP levels, but consider the presence of RF, TOD and/or established CVD.

Treatment decision making Approach to stages 2 and 3 and/or high-risk hypertensives

Individuals with BP ≥ 160/100 mm Hg and/or high CV risk, even if stage 1, should begin immediately drug treatment associated with non-pharmacological therapy.5-9 Studies on antihypertensive drugs, most of which performed with patients with that profile, have shown efficacy in BP reduction and CV protection.5-8 Non-pharmacological therapy alone cannot reduce BP sufficiently to meet the recommended BP target,4 despite being an effective adjuvant treatment to control BP and other CVRF often present. Although the absolute benefit of therapy is higher in stages 2 and 3, it also increases the residual risk because of the frequent presence and influence of other RF and already installed TOD, neutralizing part of that benefit. This reinforces the importance of approaching CV risk globally.7-9

Approach to stage 1 hypertensives at low and intermediate risk

The last international guidelines2,3 point to a gap in the evidence favoring the impact of antihypertensive therapy on the outcome reduction of stage 1 hypertensives at low-to-intermediate risk. A meta-analysis10 of four randomized studies with a minimum duration of 1 year has included 8,912 individuals with SBP of 140-159 mm Hg and/or DBP of 90-99 mm Hg. As compared to placebo, the treatment for 5 years has not reduced total mortality, CAD, stroke or CV events, having even increased by five times the chance of adverse events. Another meta-analysis6 by the Blood Pressure Lowering Treatment Trialists' Collaboration , selecting ten randomized studies on treatment vs placebo for stage 1 hypertensives, has shown a reduction in the risk for stroke, total mortality and CVD, but had included individuals on antihypertensive therapy and/or individuals with DM. When such patients were excluded, the results lost statistical power. Later, the analysis of six studies on stage 1 SAH, involving 16,036 individuals, excluding those with DM and those on baseline antihypertensive therapy, has shown significant reductions in the risk of stroke (36%), CAD (12%), CV death (22%) and total mortality (18%). An analysis restricted to stage 1 SAH and low to intermediate risk of events (up to 5% in 10 years) has shown a reduction in the risk of those same outcomes, apparently strengthening those findings. However, the absolute benefit increased as the global CV risk increased.7-9

Recently, the HOPE-3 Study has contributed to that subject.11 In a significant population sample of 12,705 individuals at intermediate CV risk (38% hypertensive), the treatment combining candesartan and hydrochlorothiazide (16 mg/day and 12.5 mg/day, respectively) has shown a 27%-reduction in the risk of composite primary outcome (mortality, stroke and non-fatal AMI) in patients with initial SBP > 143.5 mm Hg (upper tertile). Those with lower SBP, in the first and second tertiles, however, showed no reduction in CV outcomes, and, on the contrary, the risk for the study's primary outcome tended to increase, although not significantly, in individuals of the first tertile of SBP.

The result of the HOPE-3 Study supports a recent meta-analysis on hypotensive therapy stratified by CV risk, in which a BP reduction of 4.6/3 mm Hg from baseline systolic levels around 155 mm Hg has determined an 18% reduction in the risk of outcomes.12

Thus, for stage 1 hypertensives at intermediate or low CV risk, non-pharmacological therapy should be attempted13,14 for 3 and 6 months, respectively (GR: I; LE: B), after which, the lack of BP control determines the beginning of pharmacological therapy. It is mandatory, however, to follow those individuals up with periodical assessment of adherence to the non-pharmacological measures. Once the lack of adherence or worsening of BP levels is detected, pharmacological therapy should be started. It is worth noting that the intervention in stage 1 hypertensives at low risk can prevent progression of the CV risk. Currently, the wide availability of antihypertensive drugs favors a safe and well-tolerated treatment.

 Approach to BP levels of 130-139/85-89 mm Hg

Several meta-analyses with individuals with PH have shown a greater risk of progression to SAH and of CV events in that group after adjusting for other RF.15-20 Interventions in individuals with those BP levels are justified by the finding that half of the burden attributed to BP occurs in those with SBP between 130 and 150 mm Hg.21 It is worth noting, in that BP range, the expressive number of individuals with CVD, kidney disease, DM, metabolic syndrome and multiple CVRF.21 Non-pharmacological measures are recommended for that BP range. Prospective, observational studies of lifestyle intervention have shown lower risk of developing AH in those adopting a healthy lifestyle.13,22-24 (GR: I; LE: A).

Drug treatment can be considered for prehypertensive individuals with BP of 130-139/85-89 mm Hg and previous history of CVD25 (GR: IIb; LE: B) or individuals at high CV risk with no CVD26 (GR: IIb, LE: B), but there is no evidence of benefit for those at intermediate risk.11 Studies of renin-angiotensin-aldosterone system (RAAS) blockers for individuals with BP of 130-139/85-89 mm Hg at high CV risk have shown a reduction in the incidence of AH.27,28 There is no consistent evidence of the benefit of antihypertensive therapy to CV outcomes in that group. Thus, the decision to institute pharmacological therapy should be customized.

 Approach to hypertensive elderly

The most common mechanism of AH in the elderly is wall stiffness of the large arteries, leading to a predominant increase in SBP, and maintenance or decrease in DBP. There is no study assessing the impact of antihypertensive therapy in this group with baseline SBP between 140 and 159 mm Hg. Because of the inclusion criteria of the major studies, the BP level at entrance in the study was ≥ 160 mm Hg, clearly showing the advantage of the intervention from that level onward. Lower thresholds have not been tested, leaving a gap of evidence. Presumably, the benefits demonstrated on TOD for the general population should not differ from those of the elderly population. Studies conducted with individuals aged ≥ 80 years have shown favorable results of the use of antihypertensive drugs for those with BP ≥ 160 mm Hg, especially to prevent stroke and HF.29,30 Thus, antihypertensive pharmacological therapy in the elderly should begin from SBP levels ≥ 140 mm Hg onward, as long as well tolerated and considering the individual's general conditions.31 (GR: IIb; LE: B).

In very old individuals (aged ≥ 80 years), the threshold to begin pharmacological therapy increases to SBP ≥ 160 mm Hg.29,30 (GR: I; LE: A).

 Approach to youngsters with isolated systolic hypertension

The ISH is frequent among healthy male youngsters aged < 30 years and can be associated with normal central BP. In such cases, the treatment yields no significant benefits,32 and non-pharmacological measures should be adopted, with TOD monitoring. When managing ISH, pharmacological therapy should begin immediately if the CV risk is high. If DBP elevation occurs, the same criteria for the treatment of the general population should be adopted.

Tables 1 and 2 show the grades of recommendation and levels of evidence for beginning the treatment.

Recommendations to begin antihypertensive therapy: lifestyle interventions and pharmacological therapy
Situation Population (casual measure) Recommendation Class Level of evidence
Beginning of lifestyle interventions All hypertension stages and BP of 135-139/85-89 mm Hg At the time of diagnosis I A
Beginning of pharmacological therapy Stage 2 and 3 hypertensives At the time of diagnosis I A
Stage 1 hypertensives and high CV risk At the time of diagnosis I B
Elderly hypertensivesaged < 80 years SBP ≥140 mmHg IIa B
Elderly hypertensivesaged ≥ 80 years SBP ≥160 mmHg IIa B
Stage 1 hypertensives and intermediate or low CV risk Wait 3-6 months for the effect of lifestyle interventions IIa B
Individuals with BP of 130-139/85-89 mm Hg and preexisting CVD or high CV risk At the time of diagnosis IIb B
Individuals with BP of 130-139/85-89 mm Hg and no preexisting CVD and low or intermediate CV risk Not recommended III -

BP: blood pressure; SBP: systolic blood pressure; CV: cardiovascular; CVD: cardiovascular disease.

 Blood pressure targets to be met according to individual characteristics
Category Target recommended Class Level of evidence
Stage 1 and 2 hypertensives with intermediate or low CV risk and stage 3 AH < 140/90 mm Hg I A
Stage 1 and 2 hypertensives with high CV risk < 130/80 mm Hg* I A**

CV: cardiovascular; AH: arterial hypertension.

For patients with CAD, BP should not be < 120/70 mm Hg, particularly those with DBP < 60 mm Hg, because of the risk of coronary hypoperfusion, myocardial damage and CV events.

For diabetic patients, the class of recommendation is IIb, level of evidence B.

 BP targets

Recent international guidelines2,3 have recommended more conservative BP targets for the elderly and those at high CV risk, such as diabetic individuals, mainly because of the lack of evidence supporting recommendations for different types of patients. However, meta-analyses7,9 and the SPRINT Study31 have suggested reviewing those recommendations. A meta-analysis7 of 32 controlled and randomized studies with 104,359 individuals with different initial BP levels (stages 1 to 3) has compared the impact of the BP levels obtained (SBP: < 150 mm Hg, < 140 mm Hg and < 130 mm Hg; and DBP: < 90 mm Hg and < 80 mm Hg) on total and CV mortality and CV outcomes (stroke, CAD and HF). The BP reduction to 140-149 mm Hg (mean, 143.3 mm Hg) as compared to > 150 mm Hg has shown a significant decrease in the risk of total and CV mortality, stroke, CAD and HF. The comparison of the SBP levels obtained of 30-139 mm Hg (mean, 137.2 mm Hg) with values > 140 mm Hg has shown reductions in the risk of total and CV mortality, stroke, CAD, but not of HF. In addition, the comparison of the SBP levels achieved of 120-129 mm Hg (mean, 126.8 mm Hg) with those > 130 mm Hg has revealed a reduction in the risk of total mortality and stroke. The same analysis carried out for DBP revealed that DBP of 80-89 mm Hg (mean, 86.6 mm Hg) as compared to > 90 mm Hg reduced the risk of total and CV mortality, stroke, CAD and HF, while DBP of 70-79 mm Hg (mean, 78.5 mm Hg) as compared to > 80 mm Hg reduced the risk of only stroke. Thus, the BP target < 140/90 mm Hg has unequivocal benefits in reducing the risk of CV mortality and outcomes, and the BP target < 130/80 mm Hg is safe and provides more protection against stroke.

The randomized, controlled clinical trial SPRINT31 has included 9,361 individuals > 50 years, with SBP of 130-180 mm Hg and high CV risk (risk ≥ 15% within 10 years by the Framingham score, CVD, kidney disease or ≥ 75 years), excluding those with DM, polycystic kidney disease or previous stroke. The study population was randomized for more intense (< 120 mm Hg) and less intense (< 140 mmHg) SBP reduction. The composite primary outcome was the occurrence of AMI or other acute coronary syndrome, stroke, HF and CV death. In the first year, the BP levels achieved were 121.4/68.7 mm Hg and 136.2/76.3 mm Hg, respectively. The early interruption of the study in 3.26 years was due to the benefit demonstrated in the more intense SBP treatment arm, with a 25% reduction in the risk of the study's primary outcome as compared to that of the less intense SBP treatment arm (1.65%/year vs 2.19%/year, HR = 0.75; 95% confidence interval: 0.64-0.89; p < 0.001). In addition, the more intense treatment group had a 27% reduction (HR = 0.73; 95% confidence interval: 0.60-0.90; p = 0.003) in the risk of total mortality. The benefit was demonstrated in pre-specified subgroups. The incidence of adverse events, mainly hypotension, syncope, electrolyte disorders and acute kidney injury, was higher in the group with more intense BP reduction. In individuals ≥ 75 years, the occurrence of adverse events was similar to that in the entire population studied. Despite the greater rate of severe adverse events, the CV benefits and the benefits on mortality overlapped the risks of adverse events.

There is a major controversy regarding diabetic patients. The ACCORD study,33 including 4,733 diabetic patients, also randomized for SBP reduction < 120 mm Hg and < 140 mm Hg, could not reduce significantly the risk of the study's primary outcome (HR = 0.88; 95% confidence interval: 0.73-1.06; p = 0.20), and, thus, does not support the recommendations for stricter BP targets in that group of patients. In the ACCORD study,33 the SBP means achieved in the first year of treatment were 119.3 mm Hg and 133.5 mm Hg for the arms of greater and smaller SBP reductions, respectively. In addition, it is worth noting that, even with a small number of events, the more intense treatment arm reduced the risk of stroke by 41% (HR = 0.59; 95% confidence interval: 0.39-0.89; p = 0.01) and had a low incidence of adverse events.

Several differences in the conception of the SPRINT31 and ACCORD33 studies indicate the need for caution when interpreting their apparently different conclusions: the number of patients recruited in the ACCORD study was almost half that of the SPRINT study and with a lower mean age. The SPRINT study included older individuals (28% ≥ 75 years) and with CKD. The 2X2 factorial design of the ACCORD study, simultaneously assessing the effect of glycemic control, might have contributed to reduce the statistical power of the population sample, because, in later analyses, the sample restriction to individuals with strict BP control regardless of their serum glucose levels has revealed a 26% risk reduction, in accordance with the SPRINT data.31 Therefore, the findings suggest that the divergence in the results of the two studies could have been due to differences in study design, interactions between treatments, or to chance. However, specific changes in arteriolar function and blood flow in DM could have influenced the difference between the results of the two studies. Regarding DBP, the HOT study34 has shown, in diabetic patients, a 51% reduction in the risk of major CV outcomes in the treatment arm aimed at reaching DBP < 80 mm Hg (actual mean achieved: 81 mm Hg) as compared to the treatment arm aimed at reaching DBP < 90 mm Hg.

Based on the results of clinical trials and systematic reviews cited, this guideline chose to recommend a BP target lower than 130/80 mm Hg for patients at high CV risk. Exceptions apply to two situations: 1) for diabetic patients - so far considered as at high risk - that PB target was not supported by the results of the ACCORD study, therefore, the recommendation was defined as GR: IIb; LE: B; 2) for patients with CAD, recent records and cohort studies have shown an increase in fatal and non-fatal CV events,35 in addition to an increase in troponin36 when BP levels were < 120/70 mm Hg, especially DBP < 60 mm Hg.36 Thus, for those patients, BP target should be within a narrower safe range (< 130/80 mm Hg, but not < 120/70 mm Hg).

The BP target of stage 3 hypertensive individuals, despite their high CV risk, should be < 140/90 mm Hg,7 because there is no scientific evidence supporting greater BP reductions. (GR: I; LE: A).

For elderly hypertensives ≥ 80 years, there is no evidence of benefits deriving from BP levels < 140 mm Hg, in addition to the increased likelihood of adverse effects. The HYVET Study supports the recommendation of BP target < 150/90 mm Hg with a reduction in the risk for stroke and HF.30 The presence of ISH requires care regarding the excessive reduction in DBP, which should be maintained over 60 mm Hg or even over 65 mm Hg in the presence of CAD.34 (GR: IIb; LE: B). In the SPRINT Study, the elderly aged ≥ 75 years allocated to the more intense BP treatment arm (mean SBP achieved, 123.4 mm Hg) as compared to the group of standard SBP reduction (mean BP achieved, 134.8 mm Hg) had a 24% reduction in the risk of the study's primary outcome, regardless of the degree of fragility, and no increase in the number of adverse events in relation to the rest of the study population.37 Thus, the BP targets for the elderly should be defined in the same way they are for other adults; however, BP reduction should be performed carefully and considering the presence of comorbidities and the use of multiple medications.

Table 1 shows the major recommendations for BP targets.

Hypertensives without proper BP control should undergo monthly medical assessments, aimed at reaching the BP target recommended as soon as possible by using sequential therapeutic adjustments. Whenever possible, BP control should be confirmed with outside-the-office BP measurements, by use of either 24-hour ABPM or HBPM. In the elderly and those with significant BP elevations, BP levels should be reduced carefully and progressively, on a case-by-case basis, depending on the patient's general conditions, presence of comorbidities and of concomitant medication.

 References 1 Sociedade Brasileira de Cardiologia; Sociedade Brasileira de Hipertensão; Sociedade Brasileira de Nefrologia. [VI Brazilian Guidelines on Hypertension]. Arq Bras Cardiol. 2010;95(1 Suppl):1-51. Erratum in: Arq Bras Cardiol. 2010;95(4):553. Sociedade Brasileira de Cardiologia Sociedade Brasileira de Hipertensão Sociedade Brasileira de Nefrologia VI Brazilian Guidelines on Hypertension nullErratum in Arq Bras Cardiol. 2010;95(4):553. Arq Bras Cardiol 2010 95 1 Suppl 1 51 2 Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-357. Mancia G Fagard R Narkiewicz K Redon J Zanchetti A Böhm M Task Force Members 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J Hypertens 2013 31 7 1281 1357 3 James PA, Oparil S, Carter BL, Cushman WC, Dennison_Himmelfard C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-20. James PA Oparil S Carter BL Cushman WC Dennison_Himmelfard C Handler J 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) JAMA 2014 311 5 507 520 4 Lin JS, O'Connor EA, Evans CV, Senger CA, Rowland MG, Groom HC. Behavioral counseling to promote a healthy lifestyle for cardiovascular disease prevention in persons with cardiovascular risk factors: an updated systematic evidence review for the US Preventive Services Task Force. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014. Lin JS O'Connor EA Evans CV Senger CA Rowland MG Groom HC Behavioral counseling to promote a healthy lifestyle for cardiovascular disease prevention in persons with cardiovascular risk factors: an updated systematic evidence review for the US Preventive Services Task Force Rockville (MD) Agency for Healthcare Research and Quality (US) 2014 5 Collins R, MacMahon S. Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease. Br Med Bull. 1994;50(2):272-98. Collins R MacMahon S Blood pressure, antihypertensive drug treatment and the risks of stroke and of coronary heart disease Br Med Bull 1994 50 2 272 298 6 Sundstrom J, Arima H, Jackson R, Turnbull, Rahimi K, Chalmers J, et al. Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis. Ann Intern Med. 2015;162(3):184-91. Sundstrom J Arima H Jackson R Turnbull Rahimi K Chalmers J Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis Ann Intern Med 2015 162 3 184 191 7 Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 2. Effects at different baseline and achieved blood pressure levels--overview and meta-analyses of randomized trials. J Hypertens. 2014;32(12):2296-304. Thomopoulos C Parati G Zanchetti A Effects of blood pressure lowering on outcome incidence in hypertension. 2. Effects at different baseline and achieved blood pressure levels--overview and meta-analyses of randomized trials J Hypertens 2014 32 12 2296 2304 8 Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 3. Effects in patients at different levels of cardiovascular risk-overview and meta-analyses of randomized trials. J Hypertens. 2014;32(12):2305-14. Thomopoulos C Parati G Zanchetti A Effects of blood pressure lowering on outcome incidence in hypertension. 3. Effects in patients at different levels of cardiovascular risk-overview and meta-analyses of randomized trials J Hypertens 2014 32 12 2305 2314 9 Zanchetti A, Thomopoulos C, Parati G. Randomized controlled trials of blood pressure lowering in hypertension: a critical reappraisal. Circ Res. 2015;116(6):1058-73. Zanchetti A Thomopoulos C Parati G Randomized controlled trials of blood pressure lowering in hypertension: a critical reappraisal Circ Res 2015 116 6 1058 1073 10 Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev. 2012 Aug 15;(8):CD006742. Diao D Wright JM Cundiff DK Gueyffier F Pharmacotherapy for mild hypertension Cochrane Database Syst Rev 2012 8 15 8 CD006742 CD006742 11 Lonn EM, Bosch J, Lopez-Jaramillo P, Zhu J, Liu L, Pais P, et al. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2009-20. Lonn EM Bosch J Lopez-Jaramillo P Zhu J Liu L Pais P Blood-pressure lowering in intermediate-risk persons without cardiovascular disease N Engl J Med 2016 374 21 2009 2020 12 Sundstrom J, Arima H, Woodward M, JAckson R, Karnmali K, lloyd-Jones D, et al. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 2014;384(9943):591-8. Sundstrom J Arima H Woodward M JAckson R Karnmali K lloyd-Jones D Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data Lancet 2014 384 9943 591 598 13 Elmer PJ, Obarzanek E, Vollmer WM, Simons-Morton D, Stevens VJ, Young DR, et al. Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial. Ann Intern Med. 2006;144(7):485-95. Elmer PJ Obarzanek E Vollmer WM Simons-Morton D Stevens VJ Young DR Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial Ann Intern Med 2006 144 7 485 495 14 Frisoli TM, Schmieder RE, Grodzicki T, Messerli FH. Beyond salt: lifestyle modifications and blood pressure. Eur Heart J. 2011;32(24):3081-7. Frisoli TM Schmieder RE Grodzicki T Messerli FH Beyond salt: lifestyle modifications and blood pressure Eur Heart J 2011 32 24 3081 3087 15 Egan BM, Stevens-Fabry S. Prehypertension--prevalence, health risks, and management strategies. Nat Rev Cardiol. 2015;12(5):289-300. Egan BM Stevens-Fabry S Prehypertension--prevalence, health risks, and management strategies Nat Rev Cardiol 2015 12 5 289 300 16 Huang Y, Wang S, Cai X, Mai W, Hu Y, TAng H, et al. Prehypertension and incidence of cardiovascular disease: a meta-analysis. BMC Med. 2013;11:177. Huang Y Wang S Cai X Mai W Hu Y TAng H Prehypertension and incidence of cardiovascular disease: a meta-analysis BMC Med 2013 11 177 177 17 Guo X, Zhang X, Guo L, Li Z, Zheng L, Yu S, et al. Association between pre-hypertension and cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Curr Hypertens Rep. 2013;15(6):703-16. Guo X Zhang X Guo L Li Z Zheng L Yu S Association between pre-hypertension and cardiovascular outcomes: a systematic review and meta-analysis of prospective studies Curr Hypertens Rep 2013 15 6 703 716 18 Guo X, Zhang X, Zheng L, Guo L, Li Z, Yu S, et al. Prehypertension is not associated with all-cause mortality: a systematic review and meta-analysis of prospective studies. PloS One. 2013;8(4):e61796. Guo X Zhang X Zheng L Guo L Li Z Yu S Prehypertension is not associated with all-cause mortality: a systematic review and meta-analysis of prospective studies PloS One 2013 8 4 e61796 19 Huang Y, Su L, Cai X, Mai W, Wang S, Hu Y, et al. Association of all-cause and cardiovascular mortality with prehypertension: a meta-analysis. Am Heart J. 2014;167(2):160-8. e1. Huang Y Su L Cai X Mai W Wang S Hu Y Association of all-cause and cardiovascular mortality with prehypertension: a meta-analysis Am Heart J 2014 167 2 160 168 e1 20 Huang Y, Cai X, Li Y, Su L, Mai W, Wang S, et al. Prehypertension and the risk of stroke: a meta-analysis. Neurology 2014;82(13):1153-61. Huang Y Cai X Li Y Su L Mai W Wang S Prehypertension and the risk of stroke: a meta-analysis Neurology 2014 82 13 1153 1161 21 Rodgers A, Ezzati M, Vander Hoorn S, Lopez AD, Lin RB, Murray CJ; Comparative Risk Assessment Collaborating Group. Distribution of major health risks: findings from the Global Burden of Disease study. PLoS Med. 2004;1(1):e27. Rodgers A Ezzati M Vander Hoorn S Lopez AD Lin RB Murray CJ Comparative Risk Assessment Collaborating Group Distribution of major health risks: findings from the Global Burden of Disease study PLoS Med 2004 1 1 e27 22 Forman JP, Stampfer MJ, Curhan GC. Diet and lifestyle risk factors associated with incident hypertension in women. JAMA. 2009;302(4):401-11. Forman JP Stampfer MJ Curhan GC Diet and lifestyle risk factors associated with incident hypertension in women JAMA 2009 302 4 401 411 23 Whelton PK, Appel LJ, Espeland MA, Applegate WB, Sttinger WH Jr, Kostis JB, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group. JAMA. 1998;279(11):839-46. Whelton PK Appel LJ Espeland MA Applegate WB Sttinger WH Jr Kostis JB Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group JAMA 1998 279 11 839 846 24 Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group. Arch Intern Med. 1997;157(6):657-67. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II The Trials of Hypertension Prevention Collaborative Research Group Arch Intern Med 1997 157 6 657 667 25 Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA. Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA. 2011;305(9):913-22. Thompson AM Hu T Eshelbrenner CL Reynolds K He J Bazzano LA Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis JAMA 2011 305 9 913 922 26 Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145-53. Yusuf S Sleight P Pogue J Bosch J Davies R Dagenais G Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators N Engl J Med 2000 342 3 145 153 27 Julius S, Nesbitt S, Egan B, Kaciroti N, Schork MA, Grozinski M, et al. Trial of preventing hypertension: design and 2-year progress report. Hypertension. 2004;44(2):146-51. Julius S Nesbitt S Egan B Kaciroti N Schork MA Grozinski M Trial of preventing hypertension: design and 2-year progress report Hypertension 2004 44 2 146 151 28 Luders S, Schrader J, Berger J, Unger T, Zidek W, Böhm M, et al; PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure: a prospective, randomized, controlled prevention trial of the German Hypertension League. J Hypertens. 2008;26(7):1487-96. Luders S Schrader J Berger J Unger T Zidek W Böhm M PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure: a prospective, randomized, controlled prevention trial of the German Hypertension League J Hypertens 2008 26 7 1487 1496 29 Gueyffier F, Bulpitt C, Boissel JP, Schron E, Ekbom T, Fagard R, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet. 1999;353(9155):793-6. Gueyffier F Bulpitt C Boissel JP Schron E Ekbom T Fagard R Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group Lancet 1999 353 9155 793 796 30 Beckett NS, Peters R, Fletcher AE, Stalssen JA, Liu L, Dumitrascu D, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887-98. Beckett NS Peters R Fletcher AE Stalssen JA Liu L Dumitrascu D Treatment of hypertension in patients 80 years of age or older N Engl J Med 2008 358 18 1887 1898 31 Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al; SPRINT Research Group. A Randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-16. Wright JT Jr Williamson JD Whelton PK Snyder JK Sink KM Rocco MV SPRINT Research Group A Randomized trial of intensive versus standard blood-pressure control N Engl J Med 2015 373 22 2103 2116 32 O'Rourke MF, Adji A. Guidelines on guidelines: focus on isolated systolic hypertension in youth. J Hypertens. 2013;31(4):649-54. O'Rourke MF Adji A Guidelines on guidelines: focus on isolated systolic hypertension in youth J Hypertens 2013 31 4 649 654 33 Margolis KL, O'Connor PJ, Morgan TM, Buse JB, Cohen RM, Cushman WC, et al. Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial. Diabetes Care, 2014;37(6):1721-8. Margolis KL O'Connor PJ Morgan TM Buse JB Cohen RM Cushman WC Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial Diabetes Care 2014 37 6 1721 1728 34 Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT StudyGroup. Lancet. 1998;351(9118):1755-62. Hansson L Zanchetti A Carruthers SG Dahlöf B Elmfeldt D Julius S Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT StudyGroup Lancet 1998 351 9118 1755 1762 7ª Diretriz Brasileira de Hipertensão Arterial: Capítulo 5 - Decisão e Metas Terapêuticas Malachias MVB Andrea Araujo Brandão AA Kaiser S Moreira O Filho Introdução

A abordagem terapêutica da PA elevada inclui medidas não medicamentosas e o uso de fármacos anti-hipertensivos, a fim de reduzir a PA, proteger órgãos-alvo, prevenir desfechos CV e renais.1-3 Medidas não medicamentosas têm se mostrado eficazes na redução da PA, apesar de limitadas pela perda de adesão a médio e longo prazo. Revisão sistemática4 de estudos com duração mínima de 12 a 24 meses, combinando intervenções dietéticas e atividade física de média a alta intensidade, em pacientes usando ou não medicações revelou redução da PAS e da PAD por período < 12 meses de -4,47 (-7,91 a -1,04) mmHg e de -1,10 (-2,39 a 0,19) mmHg, respectivamente. Para períodos de 12 a 24 meses, as reduções observadas foram de -2,29 (-3,81 a -0,76) mmHg e de -1,00 (-3,22 a 1,22) mmHg, respectivamente para PAS e PAD. O impacto direto dessas medidas sobre o risco de desfechos CV é incerto, os estudos são pequenos e breves e os efeitos sobre outros FR poderiam contribuir para a proteção CV.

Por outro lado, resultados de estudos clínicos controlados e randomizados com uso de fármacos anti-hipertensivos placebo-controlados em hipertensos demonstraram claramente redução significativa de mortalidade CV, AVE, infarto do miocárdio e IC. Cabe destacar que a maioria desses estudos avaliou indivíduos com idade ≥ 55 anos, de alto risco CV e tempo de seguimento de 3 a 6 anos, limitando, portanto, a extrapolação desses benefícios para o tratamento de longo prazo e em pacientes com outras características.

A decisão terapêutica deve basear-se não apenas no nível da PA, mas considerar também a presença de FR, LOA e/ou DCV estabelecida.

Decisão de Tratamento Abordagem de hipertensos estágios 2 e 3 e/ou de alto risco

Indivíduos com PA ≥ 160/100 mmHg e/ou portadores de risco CV estimado alto, mesmo no estágio 1, devem iniciar de imediato o tratamento medicamentoso associado à terapia não medicamentosa.5-9 Estudos com fármacos anti-hipertensivos, a maioria realizada com esse perfil de pacientes, demonstraram eficácia na redução da PA e proteção CV.5-8 Admite-se que a terapia não farmacológica isoladamente não possa promover reduções da PA suficientes para alcance da meta pressórica recomendada,4 apesar de constituir efetivo adjuvante no controle da PA e de outros FRCV frequentemente presentes. Embora o benefício absoluto da terapia seja maior nos estágios 2 e 3, também aumenta o risco residual devido à frequente presença e influência de outros FR e LOA já instalada, neutralizando parte desse benefício. Essa observação reforça a importância de se abordar o risco CV de forma global.7-9

Abordagem de hipertensos estágio 1 de risco baixo e moderado

As últimas diretrizes internacionais2,3 apontaram uma lacuna no rol de evidências em favor do impacto da terapia anti-hipertensiva sobre a redução de desfechos em hipertensos estágio 1 de risco baixo e moderado. Meta-análise10 de quatro estudos randomizados com duração de ao menos 1 ano incluiu 8912 indivíduos com PAS 140-159 mmHg e/ou PAD 90-99 mmHg. Em comparação a placebo, após 5 anos, o tratamento não reduziu mortalidade total, DAC, AVE ou eventos CV e ainda aumentou em cerca de cinco vezes a chance de eventos adversos. Outra meta-análise6 do grupo Blood Pressure Lowering Treatment Trialists' Collaboration selecionou 10 estudos randomizados de tratamento vs placebo em hipertensos estágio 1 e demonstrou benefícios na redução do risco de AVE, mortalidade total e DCV, mas incluiu na avaliação indivíduos em uso de terapia anti-hipertensiva e/ou diabéticos. Com a exclusão desses pacientes, os resultados perderam poder estatístico. Posteriormente, a análise de seis estudos com HAS estágio 1, envolvendo 16.036 indivíduos, excluindo diabéticos e uso basal de terapia anti-hipertensiva, mostrou reduções significativas no risco de AVE (36%), DAC (12%), morte CV (22%) e mortalidade total (18%). Uma análise restrita a HAS estágio 1 e risco baixo a moderado de eventos (até 5% em 10 anos) demonstrou benefícios na redução do risco desses mesmos desfechos, aparentemente conferindo robustez a esses achados. Já o benefício absoluto foi tanto maior quanto maior o risco CV global.7-9

Recentemente, o estudo HOPE 3 trouxe contribuição para esse tema.11 Numa expressiva amostra populacional de 12.705 indivíduos de risco CV moderado (38% hipertensos), o tratamento com a combinação de 16 mg/dia de candesartana e 12,5 mg/dia de hidroclorotiazida mostrou que pacientes com PAS inicial acima de 143,5 mmHg (tercil superior) apresentaram redução de 27% no risco do desfecho primário composto (mortalidade, AVE e IAM não fatais). Já naqueles com PAS mais baixa, situados no primeiro e segundo tercis, não se observou redução de desfechos CV e, pelo contrário, o risco do desfecho primário do estudo tendeu a aumentar nos integrantes do tercil inferior de PAS, porém de modo não significativo.

O resultado do HOPE-3 suporta recente meta-análise de terapia hipotensora estratificada segundo o risco CV, onde a redução de 4,6/3 mmHg na PA a partir de cifras basais sistólicas em torno de 155 mmHg proporcionou redução de 18% no risco de desfechos.12

Assim, em hipertensos estágio 1 e moderado ou baixo risco CV, a terapia não farmacológica deve ser tentada13,14 por 3 e 6 meses, respectivamente (GR: I; NE: B), findos os quais, a falta de controle da PA condicionará o início de terapia farmacológica. Faz-se imperativo, contudo, acompanhar esses indivíduos com avaliação periódica da adesão às medidas não farmacológicas. Constatada a falta de adesão ou a piora dos valores pressóricos, dever-se-á iniciar precocemente a terapia farmacológica. Vale destacar que a intervenção em hipertensos de baixo risco no estágio 1 pode prevenir a progressão para um risco CV mais elevado. Atualmente, a farta disponibilidade de fármacos anti-hipertensivos favorece o tratamento seguro e bem tolerado.

 Abordagem para níveis de PA de 130-139/85-89 mmHg

Há várias meta-análises em portadores de PH mostrando maior risco de progressão para HAS e de eventos CV nesse grupo, após ajuste para os demais FR.15-20 Como justificativa para intervenções em pessoas com esses níveis pressóricos, destaca-se a constatação de que metade do ônus atribuível à PA ocorre naqueles com cifras sistólicas entre 130 e 150 mmHg.21 Importante notar, nessa faixa de PA, a existência de expressivo contingente de portadores de DCV, doença renal, DM, síndrome metabólica e de múltiplos FRCV.21 Recomendam-se medidas não medicamentosas para essa faixa pressórica. Estudos prospectivos, observacionais e de intervenção sobre estilo de vida, demonstraram menor risco de desenvolvimento de HA nos que adotavam hábitos de vida saudável.13,22-24 (GR: I; NE: A).

O tratamento medicamentoso pode ser considerado nos pré-hipertensos com PA de 130-139/85-89 mmHg e história prévia de DCV25 (GR: IIb; NE: B) ou naqueles com risco CV alto, sem DCV26 (GR: IIb, NE: B), mas não há evidências de benefício naqueles com risco moderado.11 Estudos com bloqueadores do sistema renina-angiotensina-aldosterona (SRAA) em indivíduos com PA de 130-139/85-89mmHg de alto risco CV mostraram redução da incidência de HA.27,28 Não há evidências consistentes do benefício da terapia anti-hipertensiva sobre desfechos CV nesse grupo. Portanto, a decisão de instituir terapia farmacológica deve ser individualizada.

 Abordagem de Hipertensos Idosos

O mecanismo mais comum da HA no idoso é o enrijecimento da parede arterial dos grandes vasos, levando a aumento predominante da PAS, com manutenção ou queda da PAD. Não há estudos avaliando o impacto da terapia anti-hipertensiva nesse grupo com PAS basal entre 140 e 159 mmHg. Talvez em função de critérios de inclusão dos principais estudos, o valor da PA para entrada no estudo foi ≥ 160 mmHg, com clara demonstração de vantagem da intervenção a partir desse limiar. Limiares mais baixos não foram testados, deixando um hiato de evidência. Presumivelmente, os benefícios demonstrados sobre LOA na população geral não deveriam ser diferentes daqueles na população idosa. Em indivíduos ≥ 80 anos, realizaram-se estudos com fármacos anti-hipertensivos naqueles com PA ≥ 160 mmHg, com demonstração de resultados favoráveis, em especial na prevenção de AVE e IC.29,30 Assim, recomenda-se o início da terapia farmacológica anti-hipertensiva em idosos a partir de níveis de PAS ≥ 140 mmHg, desde que bem tolerado e avaliando-se as condições gerais do indivíduo.31 (GR: IIb; NE: B).

Nos muito idosos, ou seja, naqueles com idade ≥ 80 anos, o limite para início da terapia farmacológica aumenta para uma PAS ≥ 160 mmHg.29,30 (GR: I; NE: A).

 Abordagem de Jovens com Hipertensão Sistólica Isolada

A HSI é frequente em jovens saudáveis do sexo masculino com menos de 30 anos e pode estar associada à pressão central normal. Nesses casos, o tratamento não teria benefícios significativos,32 sendo recomendada a adoção de medidas não medicamentosas, com monitorização de LOA. O tratamento da HSI deve ter início imediato de terapia farmacológica caso seu risco CV seja alto. No caso de elevação da PAD, adotam-se os mesmos critérios de tratamento da população em geral.

As Tabelas 1 e 2 apresentam as recomendações e níveis de evidências para o início de tratamento.

Recomendações para início de terapia anti-hipertensiva: Intervenções no estilo de vida e terapia farmacológica
Situação Abrangência (medida casual) Recomendação Classe Nível de evidência
Início de intervenções no estilo de vida Todos os estágios de hipertensão e PA 135- 139/85-89 mmHg Ao diagnóstico I A
Início de terapia farmacológica Hipertensos estágio 2 e 3 Ao diagnóstico I A
Hipertensos estágio 1 e alto risco CV Ao diagnóstico I B
Hipertensos idosos com idade até 79 anos PAS ≥140 mmHg IIa B
Hipertensos idosos com idade ≥ 80 anos PAS ≥160 mmHg IIa B
Hipertensos estágio 1 e risco CV moderado ou baixo Aguardar 3 a 6 meses pelo efeito de intervenções no estilo de vida IIa B
Indivíduos com PA 130-139/85-89 mmHg e DCV preexistente ou alto risco CV Ao diagnóstico IIb B
Indivíduos com PA 130-139/85-89 mmHg sem DCV pré-existente e risco CV baixo ou moderado Não recomendado III -

PA: pressão arterial; PAS: pressão arterial sistólica; CV: cardiovascular; DCV: doença cardiovascular.

 Metas a serem atingidas em conformidade com as características individuais
Categoria Meta recomendada Classe Nível de Evidência
Hipertensos estágios 1 e 2, com risco CV baixo e moderado e HA estágio 3 < 140/90 mmHg I A
Hipertensos estágios 1 e 2 com risco CV alto < 130/80 mmHg* I A**

CV: cardiovascular; HA: hipertensão arterial.

Para pacientes com doenças coronarianas, a PA não deve ficar < 120/70 mmHg, particularmente com a diastólica abaixo de 60 mmHg pelo risco de hipoperfusão coronariana, lesão miocárdica e eventos cardiovasculares.

Para diabéticos, a classe de recomendação é IIB, nível de evidência B.

 Metas Pressóricas

Diretrizes internacionais2,3 recentes têm preconizado metas pressóricas mais conservadoras para idosos e aqueles com alto risco CV, incluindo diabéticos, principalmente pela falta de evidências que suportem recomendações em diferentes perfis de pacientes. Entretanto, meta-análises7,9 e o estudo SPRINT31 sugerem a revisão dessas recomendações. Meta-análise7 de 32 estudos controlados e randomizados com 104.359 indivíduos com diferentes níveis iniciais de PA (estágios 1 a 3) comparou o impacto de valores de PAS alcançados < 150 mmHg, < 140 mmHg e < 130 mmHg e de PAD < 90 mmHg e < 80 mmHg sobre mortalidade (total e CV) e desfechos CV (AVE, DAC e IC). A redução da PA a 140-149 mmHg (média 143,3 mmHg), comparada a > 150 mmHg, mostrou redução significativa do risco de mortalidade total e CV, AVE, DAC e IC. A comparação de valores atingidos de PAS de 130-139 mmHg (média 137,2 mmHg) com cifras > 140 mmHg, mostrou reduções do risco de mortalidade total e CV, AVE, DAC, mas não de IC; e a comparação de valores alcançados de PAS de 120-129 mmHg (média 126,8 mmHg) com > 130mmHg se acompanhou de redução do risco de mortalidade total e AVE. A mesma análise feita para PAD revelou que PAD de 80-89 mmHg (média 86,6 mmHg) comparada com > 90 mmHg resultava em redução do risco de mortalidade total e CV, AVE, DAC e IC, enquanto PAD de 70-79 mmHg (média 78,5 mmHg) comparada a > 80 mmHg acompanhava-se de redução do risco apenas de AVE. Assim sendo, a meta de PA <140/90 mmHg mostra benefícios inequívocos na redução de risco de mortalidade e desfechos CV, e a meta < 130/80 mmHg é segura e agrega maior proteção para o AVE.

O ensaio clínico, randomizado, controlado SPRINT31 incluiu 9.361 indivíduos > 50 anos, com PAS de 130-180 mmHg e de alto risco CV (risco ≥ 15% em 10 anos pelo escore de Framingham, DCV, doença renal ou ≥ 75 anos) exceto diabéticos, indivíduos com doença renal policística ou com AVE prévio. A população do estudo foi randomizada para redução mais intensa (< 120 mmHg) e menos intensa (< 140 mmHg) da PAS. O desfecho primário composto foi a ocorrência de IAM ou outras síndromes coronarianas agudas, AVE, IC e morte CV. No primeiro ano, a PA atingida foi de 121,4/68,7 mmHg e 136,2/76,3 mmHg, respectivamente. A interrupção precoce do estudo em 3,26 anos deveu-se ao benefício demonstrado no braço de tratamento mais intenso da PAS, com redução de 25% no risco do desfecho primário do estudo comparado àquele com redução menos intensa da PA (1,65%/ano vs 2,19%/ano, HR = 0,75; intervalo de confiança 95%: 0,64-0,89; p < 0,001). Ademais, no grupo de tratamento mais intenso, houve redução de 27% (HR = 0,73; intervalo de confiança 95%: 0,60-0,90; p = 0,003) no risco de mortalidade total. O benefício foi demonstrado nos subgrupos pré-especificados. Houve maior incidência de eventos adversos no grupo de redução mais intensa da PA, principalmente hipotensão, síncope, distúrbios eletrolíticos e injúria renal aguda. Em indivíduos ≥ 75 anos, a magnitude da ocorrência de eventos adversos foi semelhante à da população total estudada. Apesar da maior taxa de eventos adversos sérios, admite-se que os benefícios CV e sobre mortalidade se sobrepuseram aos riscos de eventos adversos.

A principal controvérsia diz respeito aos pacientes diabéticos, já que o estudo ACCORD,33 que incluiu 4733 pacientes diabéticos, randomizados também para redução de PAS < 120 mmHg e < 140 mmHg, não foi capaz de reduzir significativamente o risco do desfecho primário do estudo (HR = 0,88; intervalo de confiança 95%: 0,73-1,06; p = 0,20) e, portanto, não apoia recomendações de metas mais intensas da PA nesse grupo de pacientes. No ACCORD,33 as médias de PAS alcançadas no primeiro ano de tratamento foram 119,3 mmHg e 133,5mmHg para os braços de redução mais e menos intensa da PAS, respectivamente. Além disso, vale destacar que, mesmo com número pequeno de eventos, o braço de tratamento mais intenso reduziu o risco de AVE em 41% (HR 0,59; intervalo de confiança 95%: 0,39-0,89; p = 0,01) e apresentou baixa incidência de eventos adversos.

Várias diferenças na concepção dos estudos SPRINT31 e ACCORD33 indicam a necessidade de prudência ao interpretar as conclusões aparentemente díspares de ambos: o estudo ACCORD recrutou quase a metade de pacientes em relação ao SPRINT e com menor média etária. O SPRINT incluiu indivíduos mais idosos (28% ≥ 75 anos) e com DRC. O desenho fatorial 2X2 no estudo ACCORD, avaliando simultaneamente o efeito do controle glicêmico, possivelmente contribuiu para reduzir o poder estatístico da amostra populacional, tanto que, em análises posteriores, a restrição da amostra aos indivíduos com controle intenso da PA independentemente dos níveis glicêmicos revelou redução no risco de 26%, em linha com os dados do SPRINT.31 Portanto, os achados sugerem que a divergência entre os resultados dos dois estudos pode ter de fato decorrido de diferenças no desenho, interações entre tratamentos, ou mesmo de efeito do acaso. Entretanto, não se pode afastar que alterações específicas da função arteriolar e fluxo sanguíneo no DM possam ter influenciado a diferença entre os resultados dos dois estudos. Em relação à PAD, o estudo HOT34 demonstrou, em diabéticos, redução de 51% no risco de desfechos CV maiores no braço de tratamento destinado a alcançar PAD < 80 mmHg (média real alcançada: 81 mmHg) quando comparado ao braço de tratamento destinado a alcançar uma PAD < 90 mmHg.

Frente aos resultados de estudos clínicos e revisões sistemáticas anteriormente citados, esta diretriz optou por recomendar meta pressórica inferior a 130/80 mmHg para pacientes de alto risco CV. Ficam as ressalvas, contudo, para duas situações: 1) em diabéticos - até o presente momento encarados como de alto risco - essa meta não foi solidamente demonstrada pelos resultados do estudo ACCORD, razão pela qual o estágio de evidência da recomendação foi definido como GR: IIb; NE: B. 2) em pacientes com DAC, registros e estudos de coorte recentes mostraram um aumento de eventos CV fatais e não fatais,35 bem como aumento da troponina36 quando a pressão ficou < 120/70, particularmente com a PAD < 60mmHg.36 Dessa forma, para esses pacientes, a meta deve ficar numa faixa mais estreita de segurança (< 130/80 mmHg, mas não < 120/70 mmHg).

Hipertensos com PA no estágio 3, embora de alto risco CV, deverão ter como meta pressórica a PA < 140/90 mmHg,7 pois não há evidências científicas que suportem reduções mais intensas da PA. (GR: I; NE: A).

Para hipertensos idosos ≥ 80 anos, não há evidência de benefícios proporcionados por cifras < 140 mmHg, além de aumentar a possibilidade de efeitos adversos. O estudo HYVET suporta a recomendação de uma meta pressórica < 150/90 mmHg com redução do risco de AVE e IC.30 A presença de HSI impõe cuidado com a redução exagerada da PAD, que deverá ser prudentemente mantida acima de 60 mmHg ou mesmo 65 mmHg na presença de DAC.34 (GR: IIb ; NE:B). Em idosos com 75 anos ou mais do estudo SPRINT, aqueles alocados para o braço de tratamento mais intensivo da PA (média de PAS alcançada 123,4 mmHg) comparados ao grupo de redução padrão de PAS (média de PA alcançada 134,8 mmHg) apresentaram redução do risco do desfecho primário do estudo de 24%, independente do grau de fragilidade e sem aumento do número de eventos adversos em relação ao restante da população do estudo37. Assim, as metas de PA em idosos devem ser definidas da mesma forma que para os demais adultos, recomendando-se, no entanto, que a redução da PA seja feita de forma cautelosa e considerando-se a presença de comorbidades e de uso de múltiplos medicamentos.

As principais recomendações para as metas pressóricas são descritas na Tabela 1.

Para hipertensos sem controle adequado da PA, recomendam-se avaliações médicas mensais, com o objetivo de alcançar a meta pressórica recomendada o mais breve possível mediante ajustes terapêuticos sequenciais. Sempre que possível, o controle pressórico deve ser confirmado com medições de PA obtidas fora do consultório, seja pela MAPA de 24 horas ou por medidas residenciais da PA. Em idosos e naqueles com elevações muito significativas da PA, convém reduzir os níveis pressóricos de forma mais cautelosa, progressiva, cabendo um julgamento caso a caso, conforme as condições gerais do paciente, a presença de comorbidades e de medicação concomitante.