Clinical outcomes according to baseline blood pressure in patients with a low ejection fraction in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program.
OBJECTIVE
This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (<or=0.40) in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) program.


BACKGROUND
Hypotension is a predictor of poor prognosis in heart failure, yet many treatments shown to reduce morbidity and mortality lower blood pressure. This paradox creates a dilemma for physicians and may explain why low BP is reported as a reason for under-use of these agents.


METHODS
The interaction between treatment and baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) was examined with patients divided into 6 SBP categories (<or=100, 101 to 110, 111 to 120, 121 to 130, 131 to 140 and >or=141 mm Hg) and 4 DBP categories (<or=60, 61 to 70, 71 to 80 and >or=81 mm Hg).


RESULTS
Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP.


CONCLUSIONS
In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.
Meredith
Peter A
PA
Faculty of Medicine, University of Glasgow, Glasgow, Scotland.
Ostergren
Jan
J
Anand
Inder
I
Puu
Margareta
M
Solomon
Scott D
SD
Michelson
Eric L
EL
Olofsson
Bertil
B
Granger
Christopher B
CB
Yusuf
Salim
S
Swedberg
Karl
K
Pfeffer
Marc A
MA
McMurray
John J V
JJ
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D003971:Diastole; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007022:Hypotension / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan