Stroke reduction in hypertensive adults with cardiac hypertrophy randomized to losartan versus atenolol: the Losartan Intervention For Endpoint reduction in hypertension study.
The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the beta-blocker atenolol. We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates. Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy, random allocation to losartan-based treatment lowered the risk of fatal (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43 to 0.96; P=0.032) and atherothrombotic stroke (HR, 0.72; 95% CI, 0.59 to 0.88; P=0.001) compared with atenolol-based therapy. Although comparable risk reductions occurred for hemorrhagic and embolic stroke, these were not statistically significant. The number of neurological deficits per stroke was similar, but there were fewer strokes in the losartan group for nearly every level of stroke severity. Effects were consistent in all clinical subgroups except for those defined by age and ethnicity. The benefits of losartan on all strokes were independent of baseline and time-varying risk factors, including blood pressure. The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant, declining to 25, 24, and 9 for patients with cerebrovascular disease, isolated systolic hypertension, and atrial fibrillation, respectively. In conclusion, substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk.
Kizer
Jorge R
JR
Weill Medical College of Cornell University, New York, NY, USA. jok2007@med.cornell.edu
Dahlöf
Björn
B
Kjeldsen
Sverre E
SE
Julius
Stevo
S
Beevers
Gareth
G
de Faire
Ulf
U
Fyhrquist
Frej
F
Ibsen
Hans
H
Kristianson
Krister
K
Lederballe-Pedersen
Ole
O
Lindholm
Lars H
LH
Nieminen
Markku S
MS
Omvik
Per
P
Oparil
Suzanne
S
Wedel
Hans
H
Wachtell
Kristian
K
Edelman
Jonathan M
JM
Snapinn
Steven M
SM
Harris
Katherine E
KE
Devereux
Richard B
RB
D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications; D015897:Comorbidity; D048909:Diabetes Complications; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000150:complications*; D015994:Incidence; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001262:Atenolol; D019808:Losartan