Cardiovascular morbidity and mortality in hypertensive patients with lower versus higher risk: a LIFE substudy.
We hypothesized that losartan was superior to atenolol in reducing cardiovascular events in a lower-risk group (LRG) versus a higher-risk group (HRG) of patients in a Losartan Intervention For Endpoint reduction (LIFE) substudy, independently of blood pressure (BP) reduction. In a post hoc analysis, we designated 4282 patients as LRG on the basis of: (1) no previous cardiovascular disease (coronary, cerebral, peripheral vascular disease); (2) no diabetes; (3) no isolated systolic hypertension; and (4) inclusion of the lowest 3 quartiles of electrocardiographically documented left ventricular hypertrophy. The HRG consisted of 4911 remaining patients who did not qualify for the LRG. In the LRG, losartan was superior to atenolol in reducing stroke: hazard ratio (HR), 0.72 (95% confidence interval [CI], 0.53 to 0.98); new-onset diabetes (HR, 0.74 [95% CI, 0.58 to 0.93]; and new-onset atrial fibrillation: HR, 0.69 (95% CI, 0.51 to 0.92), all P<0.05 but not composite end points or cardiovascular mortality (both P=NS). In the HRG, losartan was superior to atenolol in reducing composite end points: HR, 0.82 (95% CI, 0.71 to 0.94), P<0.01; cardiovascular mortality: HR, 0.77 (95% CI, 0.62 to 0.95), P<0.05; stroke: HR, 0.75 (95% CI, 0.61 to 0.92), P<0.01; new-onset diabetes: HR, 0.76 (95% CI, 0.60 to 0.96), P<0.05; and new-onset atrial fibrillation: HR, 0.71 (95% CI, 0.58 to 88), P<0.05. Test for interaction of treatment with LRG versus HRG was not significant for composite end point, stroke, or atrial fibrillation, but was for cardiovascular mortality (P=0.018). Achieved systolic BP reduction favored losartan over atenolol by -1.8 mm Hg in LRG (P=NS) and -0.7 mm Hg (P=0.001) in HRG, but no significant differences occurred in diastolic or mean BP in either group. In conclusion, losartan compared with atenolol reduces the risk of stroke, new-onset diabetes, and new-onset atrial fibrillation in the LRG and the HRG.
Franklin
Stanley S
SS
Heart Disease Prevention Program, University of California, Irvine, CA 92697, USA. ssfranklinmd@earthlink.net
Wachtell
Kristian
K
Papademetriou
Vasilios
V
Olsen
Michael H
MH
Devereux
Richard B
RB
Fyhrquist
Frej
F
Ibsen
Hans
H
Kjeldsen
Sverre E
SE
Dahlöf
Björn
B
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001262:Atenolol / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000150:complications* / Q000401:mortality*; D003920:Diabetes Mellitus / Q000517:prevention & control; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000517:prevention & control
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001262:Atenolol; D019808:Losartan