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Effects of blood pressure-lowering treatment on cardiovascular outcomes and mortality: 13 – benefits and adverse events in older and younger patients with hypertension overview, meta-analyses and meta-regression analyses of randomized trials

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

doi: 10.1097/HJH.0000000000001787

Background: There is overwhelming evidence that blood pressure (BP)-lowering treatment can reduce cardiovascular outcomes also in the elderly, but some important aspects influencing medical practice are controversial as sufficient evidence has not been provided by single randomized controlled trials (RCTs), whereas evidence may result from a systematic search and meta-analysis of all available data.

Objectives: The following clinically relevant issues concerning the effects of BP lowering in older and younger individuals have been investigated: differences in benefits; the oldest and the youngest age range for which evidence of BP-lowering effects is available; the SBP level at which BP-lowering treatment should be initiated; the SBP and DBP levels treatment should be aimed at; differences in treatment burdens and harms.

Methods: A database we previously identified of 72 BP-lowering RCTs in 260 210 patients was searched for separately reported data on older and younger individuals [cutoffs of 65 (primary analyses), 70, 75, 80, 60 and 55 years). The data were further stratified according to the levels of baseline (untreated) BP, and of on-treatment achieved SBP or DBP. Seven fatal and nonfatal outcomes were considered for benefits. Burdens and harms were investigated as permanent treatment discontinuations for adverse events, and hypotension/syncope. Risk ratios and absolute risk changes were calculated by a random effects model. Effects at older and younger ages were compared by heterogeneity test.

Results: Thirty-two RCTs provided data on 96 549 patients older than 65 years, and 31 RCTs on 114 009 patients younger than 65 years. All cardiovascular outcomes were significantly reduced by treatment both in older and younger individuals, without significant age-dependent differences in relative risk reduction but with significantly higher absolute risk reductions in older individuals. The extreme age ranges for which evidence of significant benefits of treatment were available was greater than 80 and less than 55 years. Only one RCT provided data on benefits of BP-lowering at age greater than 65 when treatment was initiated at SBP values in the grade 1 range, but more consistent evidence was provided when age was greater than 60 years. Both in patients older and younger than 65 years, significant reductions of cardiovascular outcomes were found at on-treatment SBP less than 140 mmHg and DBP less than 80 mmHg. There was no evidence that treatment discontinuations for adverse events or hypotension/syncope were more frequent at age greater than 65.

Conclusion: Antihypertensive treatment should be recommended to all individuals with elevated BP, independent of age. The prudent recommendation to initiate treatment at SBP values 140–159 mmHg is supported at older age defined as greater than 60 years. SBP and DBP values lower than 140 mmHg and, respectively, 80 mmHg can be aimed at with incremental benefits without disproportionate burdens until age 80 years, above which available evidence is for benefits at on-treatment SBP 140–149 mmHg.

aDepartment of Cardiology, Helena Venizelou Hospital, Athens, Greece

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

cDepartment of Medicine and Surgery, University of Milan Bicocca

dIstituto Auxologico Italiano IRCCS, Scientific Direction

eCentro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy

Correspondence to Professor Gianfranco Parati, MD, Department of Medicine and Surgery, University of Milan Bicocca, Via L. Ariosto, 13, I-20145 Milan, Italy. Tel +39 2 619112890; fax: +39 2 619112901; e-mail:

Abbreviations: AE, discontinuation for adverse event; BP, blood pressure; CHD, coronary heart disease; CI, confidence interval; NNT, number needed to treat; RCT, randomized controlled trial; RR, risk ratio

Received 21 February, 2018

Revised 6 April, 2018

Accepted 15 April, 2018

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