Effect of valsartan on the incidence of diabetes and cardiovascular events.
BACKGROUND
It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance.


METHODS
In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization.


RESULTS
The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85).


CONCLUSIONS
Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)
John J
JJ
McMurray
Rury R
RR
Holman
Steven M
SM
Haffner
M Angelyn
MA
Bethel
Björn
B
Holzhauer
Tsushung A
TA
Hua
Yuri
Y
Belenkov
Mitradev
M
Boolell
John B
JB
Buse
Brendan M
BM
Buckley
Antonio R
AR
Chacra
Fu-Tien
FT
Chiang
Bernard
B
Charbonnel
Chun-Chung
CC
Chow
Melanie J
MJ
Davies
Prakash
P
Deedwania
Peter
P
Diem
Daniel
D
Einhorn
Vivian
V
Fonseca
Gregory R
GR
Fulcher
Zbigniew
Z
Gaciong
Sonia
S
Gaztambide
Thomas
T
Giles
Edward
E
Horton
Hasan
H
Ilkova
Trond
T
Jenssen
Steven E
SE
Kahn
Henry
H
Krum
Markku
M
Laakso
Lawrence A
LA
Leiter
Naomi S
NS
Levitt
Viacheslav
V
Mareev
Felipe
F
Martinez
Chantal
C
Masson
Theodore
T
Mazzone
Eduardo
E
Meaney
Richard
R
Nesto
Changyu
C
Pan
Rudolf
R
Prager
Sotirios A
SA
Raptis
Guy E H M
GE
Rutten
Herbert
H
Sandstroem
Frank
F
Schaper
Andre
A
Scheen
Ole
O
Schmitz
Isaac
I
Sinay
Vladimir
V
Soska
Steen
S
Stender
Gyula
G
Tamás
Gianni
G
Tognoni
Jaako
J
Tuomilehto
Alberto S
AS
Villamil
Juraj
J
Vozár
Robert M
RM
Califf
D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D003510:Cyclohexanes / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000517:prevention & control*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000178:diet therapy / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012307:Risk Factors; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D013777:Tetrazoles; D000077715:Nateglinide; D010649:Phenylalanine; D000068756:Valsartan; D014633:Valine