Pulsatile hemodynamic effects of candesartan in patients with chronic heart failure: the CHARM Program.
BACKGROUND
Abnormal large artery function and increased pulsatile load are exacerbated by excess angiotensin-II acting through the AT1 receptor and contribute to the pathogenesis and progression of chronic heart failure (CHF).


OBJECTIVE
To evaluate effects of the AT1 receptor blocker candesartan (N = 30) or placebo (N = 34) on pulsatile hemodynamics in participants with CHF in the CHARM program.


RESULTS
Noninvasive hemodynamics were assessed following 6 and 14 months of treatment and averaged. Using calibrated tonometry and aortic outflow Doppler, characteristic impedance was calculated as the ratio of the change in carotid pressure and aortic flow in early systole. Total arterial compliance was calculated by the diastolic area method. Brachial blood pressure, cardiac output and peripheral resistance did not differ between groups. Lower central pulse pressure in the candesartan group (57+/-20 vs. 67+/-17 mmHg, P = 0.043) was accompanied by lower characteristic impedance (200+/-78 vs. 240+/-74 dyne s/cm5, P = 0.039) and higher total arterial compliance (1.87+/-0.70 vs. 1.47+/-0.48 ml/mmHg, P = 0.008). Similar favorable differences were seen when analyses were stratified for ejection fraction (< or = 0.40 vs. >0.40) and baseline angiotensin converting enzyme inhibitor use.


CONCLUSIONS
Candesartan has a favorable effect on large artery function in patients with chronic heart failure.
Mitchell
Gary F
GF
Cardiovascular Engineering, Inc., 327 Fiske Street, Holliston, MA 01746, USA. GaryFMitchell@mindspring.com
Arnold
J Malcolm O
JM
Dunlap
Mark E
ME
O'Brien
Terrence X
TX
Marchiori
Gordon
G
Warner
Elaine
E
Granger
Christopher B
CB
Desai
Shashank S
SS
Pfeffer
Marc A
MA
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D002200:Capillary Resistance / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D003187:Compliance / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011673:Pulsatile Flow / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan