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.)
McMurray
John J
JJ
Holman
Rury R
RR
Haffner
Steven M
SM
Bethel
M Angelyn
MA
Holzhauer
Björn
B
Hua
Tsushung A
TA
Belenkov
Yuri
Y
Boolell
Mitradev
M
Buse
John B
JB
Buckley
Brendan M
BM
Chacra
Antonio R
AR
Chiang
Fu-Tien
FT
Charbonnel
Bernard
B
Chow
Chun-Chung
CC
Davies
Melanie J
MJ
Deedwania
Prakash
P
Diem
Peter
P
Einhorn
Daniel
D
Fonseca
Vivian
V
Fulcher
Gregory R
GR
Gaciong
Zbigniew
Z
Gaztambide
Sonia
S
Giles
Thomas
T
Horton
Edward
E
Ilkova
Hasan
H
Jenssen
Trond
T
Kahn
Steven E
SE
Krum
Henry
H
Laakso
Markku
M
Leiter
Lawrence A
LA
Levitt
Naomi S
NS
Mareev
Viacheslav
V
Martinez
Felipe
F
Masson
Chantal
C
Mazzone
Theodore
T
Meaney
Eduardo
E
Nesto
Richard
R
Pan
Changyu
C
Prager
Rudolf
R
Raptis
Sotirios A
SA
Rutten
Guy E H M
GE
Sandstroem
Herbert
H
Schaper
Frank
F
Scheen
Andre
A
Schmitz
Ole
O
Sinay
Isaac
I
Soska
Vladimir
V
Stender
Steen
S
Tamás
Gyula
G
Tognoni
Gianni
G
Tuomilehto
Jaako
J
Villamil
Alberto S
AS
Vozár
Juraj
J
Califf
Robert M
RM
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