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Destiffening effect of valsartan and atenolol: influence of heart rate and blood pressure

Boutouyrie, Pierrea,b,c; Beaussier, Hélèneb,c,d; Achouba, Assyae; Laurent, Stéphanea,b,cfor the EXPLOR trialists

doi: 10.1097/HJH.0000000000000014
ORIGINAL PAPERS: Blood vessels

Objective: We investigated data in 373 patients from the EXPLOR trial to determine the influence of heart rate (HR) and blood pressure (BP) on aortic stiffness in response to beta-blockade or angiotensin 2 type 1 receptor antagonism, administered during 24 weeks.

Methods: Carotid–femoral pulse wave velocity (PWV) was measured with aplanation tonometry (Sphygmocor ) after 8 (W8) and 24 weeks (W24) of treatment by the single-pill combination valsartan–amlodipine (80/5 mg, then 160/10 mg) or an atenolol–amlodipine combination (50/5 mg, then 100/10 mg) in a prospective, randomized, parallel-groups multicenter trial with PROBE design. Drugs were up-titrated at W8. We analyzed the changes in PWV in relation with the changes in BP and HR, and major covariates, using mixed models in each treatment arm.

Results: The unadjusted reductions in mean BP and PWV were not significantly different between groups. HR was significantly reduced in the atenolol group, but not in the valsartan group. After adjustment on BP and HR, PWV significantly decreased with valsartan [−0.37 m/s (−0.70 to −0.08) at W8 and −0.43 (−0.76 to −0.10) m/s at W24], whereas no significant change was observed after atenolol [−0.16 m/s (−0.49 to 0.17) at W8 and −0.05 (−0.35 to 0.44) m/s at W24].

Conclusion: These findings suggest that the reduction in PWV observed after atenolol could be explained by changes in BP and HR, whereas in patients treated by valsartan, about half of the decrease in aortic stiffness was BP-independent.

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aUniversité Paris Descartes, Sorbonne Paris Cité


cAssistance Publique Hôpitaux de Paris, HEGP,

dgroupe hospitalier St Joseph, Paris

eNovartis Pharma, Rueil Malmaison, France

Correspondence to Pierre Boutouyrie, MD, PhD, INSERM U970, 56 rue Leblanc, 75015 Paris, France. Tel: +33 1 5609 3966; fax: +33 1 5609 3992; e-mail:

Abbreviations: ACE, angiotensin-converting enzyme; BP, blood pressure; HR, heart rate; MBP, mean blood pressure; PP, pulse pressure; PWV, pulse wave velocity; W8, week 8; W24, week 24

Received 25 February, 2012

Revised 30 September, 2013

Accepted 30 September, 2013

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