Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study.
The beta-blocker atenolol is less effective than angiotensin-receptor blockers and calcium-channel blockers for reducing central blood pressure (BP). The trial was designed to determine whether the advantages of angiotensin-receptor blockers over atenolol remained significant when both were combined with the calcium-channel blocker amlodipine. A prospective, randomized, blinded endpoint (PROBE design) parallel group, multicenter trial including 393 patients with essential hypertension resistant to 4 weeks of 5 mg of amlodipine was set out. Central systolic BP, augmentation index (AIx; either rough or adjusted on heart rate), and carotid-to-femoral pulse wave velocity were measured with applanation tonometry (SphygmoCor) at inclusion and after 8 and 24 weeks of active treatment with an amlodipine-valsartan combination (5/80 mg and then 10/160 mg) or an amlodipine-atenolol combination (5/50 mg and then 10/100 mg). From baseline to week 24, central systolic BP decreased significantly more in the amlodipine-valsartan group (-13.70+/-1.15 mm Hg; P<0.0001) than in the amlodipine-atenolol group (-9.70+/-1.10 mm Hg; P<0.0001; difference: -4.00 mm Hg [95% CI: -7.10 to -0.90]; P=0.013), despite similar changes in brachial systolic BP. The difference in rough AIx reduction was -6.5% (95% CI: -8.3 to -4.7; P<0.0001) in favor of amlodipine-valsartan. AIx adjusted on heart rate was significantly reduced in favor of amlodipine-valsartan (-2.8% [95% CI: -4.92 to -0.68]; P<0.01). Heart rate decreased significantly more with amlodipine-atenolol (difference: -11 bpm [95% CI: -14 to -8 bpm]; P<0.001). Pulse wave velocity decreased by 0.95 m/s in both groups with no significant difference. Differences in central systolic BP and rough AIx remained significant after adjustment to the changes in heart rate. The amlodipine-valsartan combination decreased central (systolic and pulse) pressure and AIx more than the amlodipine-atenolol combination.
Boutouyrie
Pierre
P
Department of Pharmacology, INSERM U970, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France. pierre.boutouyrie@egp.aphp.fr
Achouba
Assya
A
Trunet
Patrick
P
Laurent
Stéphane
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001262:Atenolol / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011336:Probability; D011446:Prospective Studies; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013599:Systole / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan; D055815:Young Adult
D000959:Antihypertensive Agents; D013777:Tetrazoles; D017311:Amlodipine; D001262:Atenolol; D000068756:Valsartan; D014633:Valine