Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.
BACKGROUND
Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension. Left ventricular hypertrophy (LVH) is a strong independent indicator of risk of cardiovascular morbidity and death. We aimed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and, consequently, reduces cardiovascular morbidity and death.


METHODS
We did a double-masked, randomised, parallel-group trial in 9193 participants aged 55-80 years with essential hypertension (sitting blood pressure 160-200/95-115 mm Hg) and LVH ascertained by electrocardiography (ECG). We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event (death, myocardial infarction, or stroke). We used Cox regression analysis to compare regimens.


RESULTS
Blood pressure fell by 30.2/16.6 (SD 18.5/10.1) and 29.1/16.8 mm Hg (19.2/10.1) in the losartan and atenolol groups, respectively. The primary composite endpoint occurred in 508 losartan (23.8 per 1000 patient-years) and 588 atenolol patients (27.9 per 1000 patient-years; relative risk 0.87, 95% CI 0.77-0.98, p=0.021). 204 losartan and 234 atenolol patients died from cardiovascular disease (0.89, 0.73-1.07, p=0.206); 232 and 309, respectively, had fatal or non-fatal stroke (0.75, 0.63-0.89, p=0.001); and myocardial infarction (non-fatal and fatal) occurred in 198 and 188, respectively (1.07, 0.88-1.31, p=0.491). New-onset diabetes was less frequent with losartan. Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated. Losartan seems to confer benefits beyond reduction in blood pressure.
Dahlöf
Björn
B
Sahlgrenska University Hospital/Ostra, Gothenburg, Swede. bdahlof@scandinaviancri.se
Devereux
Richard B
RB
Kjeldsen
Sverre E
SE
Julius
Stevo
S
Beevers
Gareth
G
de Faire
Ulf
U
Fyhrquist
Frej
F
Ibsen
Hans
H
Kristiansson
Krister
K
Lederballe-Pedersen
Ole
O
Lindholm
Lars H
LH
Nieminen
Markku S
MS
Omvik
Per
P
Oparil
Suzanne
S
Wedel
Hans
H
D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D048909:Diabetes Complications; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001262:Atenolol; D019808:Losartan