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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

Thomopoulos, Costasa; Parati, Gianfrancob,c; Zanchetti, Albertod,e

doi: 10.1097/HJH.0000000000000379

Background: Relevant clinical questions not approached by randomized controlled trials (RCTs) of blood pressure (BP)-lowering treatment can be explored by meta-analyses stratified by clinical criteria.

Objectives: Investigating whether all grades of hypertension benefit from BP-lowering treatment and which are the target BP levels to maximize outcome reduction.

Methods: Of the 68 RCTs of intentional and nonintentional BP-lowering, those without baseline antihypertensive drugs were stratified by the average baseline SBP and DBP (hypertension grades 1, 2, and 3). RCTs with or without baseline treatment were considered for investigating the effects of mean achieved SBP/DBP across three SBP cutoffs and two DBP cutoffs. Risk ratios (RR) and 95% confidence interval (CI) (random-effects model), standardized to 10/5 mmHg SBP/DBP reduction, and absolute risk reductions of seven fatal and nonfatal outcomes were calculated. Differences between relative and absolute risk reductions in the different strata of baseline or achieved SBP/DBP were evaluated by trend or heterogeneity analyses.

Results: In 32 RCTs (104 359 individuals), significant outcome reductions were found independently of the hypertension grade, with no trend toward risk ratio changes with increasing baseline BP. A secondary analysis limited to RCTs on grade 1 hypertension at low-to-moderate risk showed significant outcome reductions [risk ratio: stroke 0.33 (0.11–0.98), coronary events 0.68 (0.48–0.95), and death 0.53 (0.35–0.80)]. In 32 RCTs (128 232 individuals), relative and absolute outcome reductions were significant for the SBP differences across 150 and 140 mmHg cutoffs. Below 130 mmHg, only stroke and all-cause death were significantly reduced. Absolute outcome reduction showed a significant trend to decrease, the lower the SBP cutoff considered. In 29 RCTs (107 665 individuals), outcomes were significantly reduced across DBP cutoffs of 90 and 80 mmHg. After excluding RCTs with baseline DBP less than 90 mmHg, only stroke reduction was significant at achieved DBP less than 80 mmHg.

Conclusion: Meta-analyses favor BP-lowering treatment even in grade 1 hypertension at low-to-moderate risk, and lowering SBP/DBP to less than 140/90 mmHg. Achieving less than 130/80 mmHg appears safe, but only adds further reduction in stroke.

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aDepartment of Cardiology, Helena Venizelou Hospital, Athens, Greece

bDepartment of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano IRCCS

cDepartment of Health Sciences, University of Milan Bicocca

dScientific Direction, Istituto Auxologico Italiano IRCCS

eCentro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Milan, Italy

Correspondence to Alberto Zanchetti, Professor, Direzione Scientifica, Istituto Auxologico Italiano, Via L. Ariosto, 13, I-20145, Milan, Italy. Tel: +39 2 619112237; fax: +39 2 619112901; e-mail:

Abbreviations: BP, blood pressure; CHD, coronary heart disease; CI, confidence interval; ESC, European Society of Cardiology; ESH, European Society of Hypertension; HF, heart failure; JNC, Joint National Committee; NICE, National Institute for Health and Clinical Excellence; NNT, number needed to treat; RCT, randomized controlled trial; RR, risk ratio

Received 7 July, 2014

Revised 6 August, 2014

Accepted 7 August, 2014

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© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins