Synergistic effect of combined HMG-CoA reductase inhibitor and angiotensin-II receptor blocker therapy in patients with chronic heart failure: the HF-COSTAR trial.
BACKGROUND
It is known that HMG-CoA reductase inhibitors (statins) may have a therapeutic benefit in patients with heart failure (HF). However, no studies have yet evaluated the possible interaction of statins and angiotensin-II receptor blockers (ARBs) on left ventricular (LV) function in patients with HF. We hypothesized that statins might alter the effect of ARBs on cardiac function in patients with HF.


RESULTS
We prospectively randomized patients with chronic HF who received the ARB, losartan (LOS group), or the statin, simvastatin (SIM), in combination with LOS (SIM+LOS group) at our hospitals and assessed before and after treatment for 6 months. Although no significant improvement of HF symptoms as evaluated by the New York Heart Association (NYHA) classification was observed in the LOS group, HF symptoms in the SIM+LOS group significantly improved. The percent increase of LV ejection fraction after treatment in the SIM+LOS group was significantly larger than in the LOS group. Furthermore, the plasma brain natriuretic peptide level was significantly lower after treatment in the SIM+LOS group than in the LOS group.


CONCLUSIONS
Combined statin and ARB therapy significantly improves both symptoms and LV function over time in patients with HF. Thus, the combination of an ARB with a statin may be a useful therapeutic strategy for HF.
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Yasuhiro
Y
Maejima
Kiyoshi
K
Nobori
Yuichi
Y
Ono
Susumu
S
Adachi
Jun-Ichi
J
Suzuki
Kenzo
K
Hirao
Mitsuaki
M
Isobe
Hiroshi
H
Ito
D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology
D057911:Angiotensin Receptor Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D019808:Losartan