Efficacy of losartan and carvedilol on central hemodynamics in hypertensives: a prospective, randomized, open, blinded end point, multicenter study

Abstract

Renin-angiotensin system (RAS) blockers have shown clinical outcomes superior to those of the beta (β)-blocker atenolol, despite similar reductions in the peripheral blood pressure (BP), perhaps because of different impacts on central hemodynamics. However, few comparative studies of RAS blockers and newer vasodilating β-blockers have been performed. We compared the central hemodynamic effects of losartan and carvedilol in a prospective, randomized, open, blinded end point study. Of the 201 hypertensive patients enrolled, 182 (49.6±9.9 years, losartan group=88 and carvedilol group=94) were analyzed. Carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), AIx corrected for a heart rate (HR) of 75 beats per minute (AIx@HR75) and central BP were measured noninvasively at baseline and after a 24-week treatment regimen with losartan or carvedilol. After 24 weeks, there were no between-group differences in the brachial BP, cfPWV, AIx@HR75 or central BP changes, except for a more favorable AIx effect with losartan. The changes in all measured metabolic and inflammatory parameters were also not significantly different between the two groups, except for uric acid. Losartan and carvedilol showed generally comparable effects on central hemodynamic indices, metabolic profile, inflammatory parameters and peripheral arterial pressure with a 24-week treatment.

Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure

“…Se excluyeron cuatro estudios porque solo comunicaban los cambios agudos de PA inducidos por el tratamiento, [27][28][29][30] 5 debido a valores incompletos de PA central basales o después del tratamiento, 12,16,25,31,32 3 debido a los criterios de inclusión, 33-35 2 por duplicar otras publicaciones, 36,37 2 por ausencia de un grupo control 38,39 y 1 porque la determinación de PA se efectuó con un dispositivo no validado. 40 En total, se incluyeron 20 estudios en el análisis cuantitativo, cuyas principales características se comunican en la Tabla 1 y la Tabla S1 del Suplemento de datos solo en línea.…”

“…Four studies were excluded for reporting only acute treatment-induced BP changes, [27][28][29][30] 5 because of incomplete central BP values at baseline or after treatment, 12,16,25,31,32 3 because of the inclusion criteria, 33-35 2 for duplicating other publications, 36,37 2 for the absence of a control group, 38,39 and 1 because central BP assessment was performed with a nonvalidated device. 40 Overall, 20 studies were included in the study for quantitative analysis, and the main characteristics are reported in Table 1 and Table S1 in the online-only Data Supplement.…”

“…Five studies had a crossover longitudinal design 21,23,[46][47][48] and reported multiple comparisons between β-blockers and other antihypertensive drugs. Among the 15 parallel group studies, 7 studies [17][18][19]21,22,24,26 compared VBB with NVBB (n=186 for nonvasodilating β-blockers, n=209 for VBB); 2 studies 49,50 compared each 2 NVBB (atenolol versus bisoprolol); in 5 trials, β-blockers (3 NVBB 51-53 and 2 VBB 40,54 ) were compared against other antihypertensive classes; and in 1 case, a NVBB was tested against placebo. 55 Other antihypertensive drug classes were concomitantly administered in 5 studies (amlodipine, 51 hydrochlorothiazide, 23,53 lisinopril, 46 and lisinopril or losartan 22 ), whereas an add-on treatment approach with prespecified or unspecified other antihypertensive drug classes was allowed in 7 cases.…”

Carvedilol binding to β2-adrenergic receptors inhibits CFTR-dependent anion secretion in airway epithelial cells

“…Carvedilol has been shown to inhibit agonist binding at ␤ 1 -and ␤ 2 -ARs and also to block norepinephrine binding to ␣ 1 -ARs to reduce vasoconstriction (25,30,37). As a result, the hemodynamic effects of carvedilol are similar to those of renin-angiotensin system blockers and significantly greater than those of conven-tional ␤-AR antagonists such as atenolol (15,17). Furthermore, carvedilol has been shown to function as an inverse agonist by blocking G protein activation while stimulating ␤-arrestinassociated signaling pathways (14).…”

Clinical relevance of central blood pressure - a critical review

“…Clinical evidence also suggests that these agents are more potent than conventional beta-blockers in reducing central systolic pressure [65,66,67], with recent studies suggesting that nebivolol is as effi cacious as ACEis, ARBs and aliskiren in this respect [56,57]. Likewise, among hypertensive patients, carvedilol and losartan reduce central pressure to a similar extent [68]. It can be assumed that a reduction of wave refl ections associated with the vasodilating properties of the newer beta-blockers may partly explain their benefi cial eff ects on central pressure.…”