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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

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

doi: 10.1097/HJH.0000000000000380

Background: Randomized controlled trials (RCTs) of blood pressure (BP) lowering lend themselves to be meta-analyzed to help providing evidence-based recommendations for hypertension treatment.

Objectives: To investigate whether relative or absolute risk reductions increase at increasing levels of baseline cardiovascular risk and whether BP-lowering treatment should be addressed to patients in risk categories promising larger absolute treatment benefits.

Methods: Sixty-eight RCTs of intentional and nonintentional BP lowering were classified in four strata of increasing average 10-year incidence of cardiovascular death in the placebo or less active treatment group: low-to-moderate risk (<5%; 23 RCTs, 81 675 individuals), high risk (5% to <10%; 11 RCTs, 46 162 individuals), very high risk (10% to <20%; 19 RCTs, 91 152 individuals), and very very high risk (≥20%; 16 RCTs, 26 881 individuals). Risk ratios and 95% confidence intervals (CIs; random-effects model) standardized to 10/5 mmHg SBP/DBP reduction, absolute risk reduction, and residual risk of seven major fatal/nonfatal outcomes were calculated. Relative and absolute risk reductions in the cardiovascular risk strata were compared by the trend analysis, residual risk by calculating odds ratio (OR) relative to low-to-moderate risk.

Results: Relative reductions of all outcomes did not differ in the risk strata, but absolute reductions significantly increased with increasing cardiovascular risk (P for trend <0.001 except for CHD): a 10/5 mmHg SBP/DBP reduction reduced the incidence of major cardiovascular events by 7 (95% CI 3–10), 30 (9–50), 56 (35–76), and 87 (62–112) events every 1000 patients treated 5 years, with increasing cardiovascular risk. However, also residual risk significantly (P < 0.001) increased with increasing cardiovascular risk [up to an OR 9.43 (8.60–10.35) for cardiovascular death]. The increase in residual risk with increasing level of cardiovascular risk persisted when RCTs with average initial age at least 65 years were excluded, and mean ages at the different cardiovascular risk levels were comparable.

Conclusion: BP-lowering treatment induces greater absolute risk reductions the higher the cardiovascular risk level, but a higher risk level is also associated with higher absolute residual risk, independent of age. Whereas reserving antihypertensive treatment to high-risk hypertensive patients maximizes the cost–benefit ratio, only treatment of low-to-moderate risk hypertensive patients may prevent the increasing number of treatment failures when treatment is initiated at higher risk.

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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; HF, heart failure; NNT, number needed to treat; OR, odds ratio; RCT, randomized controlled trial; RR, risk ratio

Received 7 July, 2014

Revised 6 August, 2014

Accepted 7 August, 2014

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