PMID- 12016625
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20020731
LR  - 20191106
IS  - 1071-9164 (Print)
IS  - 1071-9164 (Linking)
VI  - 8
IP  - 2
DP  - 2002 Apr
TI  - Comment--Val-HeFT and angiotensin-receptor blockers in perspective: A tale of the 
      blind man and the elephant.
PG  - 56-8
AB  - BACKGROUND: The role of angiotensin-receptor blockers (ARBs) in the therapy of 
      chronic heart failure (CHF) has not been clarified. There are no large 
      placebo-controlled trials with these agents. The second Evaluation of Losartan in 
      the Elderly trial (ELITE-II) compared the ARB losartan with captopril in 3,152 
      patients >/=60 years old with New York Heart Association (NYHA) class II-IV and 
      left ventricular ejection fraction </=40% and did not establish the efficacy of 
      the ARB or its equivalent to angiotensin-converting enzyme inhibitor. The 
      Valsartan Heart Failure Trial was designed to determine whether addition of 
      valsartan improved the outcomes of patients receiving standard therapy for heart 
      failure, which in most cases included an ACE inhibitor. METHODS AND RESULTS: A 
      total of 5,010 patients with NYHA class II-IV CHF and ejection fraction <40% were 
      assigned to receive 160 mg valsartan or placebo twice daily. The 2 coprimary end 
      points were all-cause mortality and the composite of mortality and morbidity, 
      defined as the incidence of hospitalization for heart failure, resuscitated 
      sudden death, or receipt of intravenous inotropic or vasodilator therapy for at 
      least 4 hours (with hospitalizations accounting for 94% of the nonfatal end 
      points). Mortality was similar in the 2 groups, but the combined mortality and 
      morbidity end point was 13.2% lower with valsartan (relative risk, 0.87; 95% 
      confidence interval, 0.77-0.97; P.009), primarily because of a reduction in the 
      number of patients hospitalized for CHF (13.8% v 18.2%). There were improvements 
      in several secondary end points, including ejection fraction, signs and symptoms 
      of CHF, and quality of life with valsartan. Of note is that analyses of subgroups 
      defined according to background therapy at baseline showed highly significant 
      interactions. For instance, the small subgroup of 366 patients (7%) who were not 
      receiving ACE inhibitors had a 33% reduction in mortality and a 44% decrease in 
      mortality and morbidity, whereas the morbidity and mortality benefit of valsartan 
      observed in the overall trial was no longer significant in patients receiving 
      background ACE inhibitor therapy (relative risk, 0.90; P.10). The larger subgroup 
      of patients receiving both an ACE inhibitor and a beta-blocker at baseline had a 
      statistically significant 42% increase in mortality with valsartan (P.009) and a 
      trend toward an increase in the mortality and morbidity composite (P.10). 
      CONCLUSIONS: When added to standard therapy, valsartan has no overall effect on 
      mortality and produces a modest (13.2%) reduction in morbidity and mortality. 
      However, this benefit is much larger in patients not receiving concomitant ACE 
      inhibitor therapy and statistically not significant in those who are taking ACE 
      inhibitors. Somewhat troublesome is the finding of significant increase in 
      mortality with valsartan in patients receiving both ACE inhibitor and 
      beta-blocker therapy.
FAU - Konstam, Marvin A
AU  - Konstam MA
AD  - Boston, Massachusetts, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Card Fail
JT  - Journal of cardiac failure
JID - 9442138
ORI - N Engl J Med. 2001 Dec 6;345(23):1667-75. PMID: 11759645
EDAT- 2002/05/23 10:00
MHDA- 2002/05/23 10:01
CRDT- 2002/05/23 10:00
PHST- 2002/05/23 10:00 [pubmed]
PHST- 2002/05/23 10:01 [medline]
PHST- 2002/05/23 10:00 [entrez]
AID - S1071916402464950 [pii]
AID - 10.1054/jcaf.2002.32950 [doi]
PST - ppublish
SO  - J Card Fail. 2002 Apr;8(2):56-8. doi: 10.1054/jcaf.2002.32950.