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Losartan More Effective Than Atenolol in Preventing Morbidity and Mortality in Low-Risk Hypertensive Patients

Losartan appears to be more effective than atenolol in preventing cardiovascular morbidity and death - especially fatal and non-fatal stroke - in patients with hypertension but without clinically evident vascular disease. Furthermore, the effect appears to be independent of blood pressure reduction.

Previous data from the Losartan Intervention for Endpoint reduction in hypertension (LIFE) trial indicates that losartan-based treatment improves cardiovascular outcomes more than atenolol-based treatment in patients with hypertension and left ventricular hypertrophy.

In the current analysis, Richard B. Devereux, MD, with the Weill Medical College of Cornell University, New York, United States and LIFE trial collaborators determined the effects of losartan versus atenolol in lower-risk participants.

The subgroup of lower-risk participants included 6,886 men and women, mean age 66 years, with essential hypertension (average sitting blood pressure, 174/98 mm Hg). Patients had electrocardiogram-defined left ventricular hypertrophy but did not have clinically evident vascular disease and were randomised to receive once-daily double-blind treatment with losartan or atenolol.

Both losartan and atenolol reduced blood pressure to the same extent. The primary composite end point (a composite of the first occurrence of cardiovascular death, stroke, or clinically evident myocardial infarction) occurred in 282 losartan-treated patients (17.5 per 1000 patient-years) and 355 atenolol-treated patients (21.8 per 1000 patient-years; relative risk, 0.81, p=0.008).

Cardiovascular death occurred in 103 losartan-treated patients and 132 atenolol-treated patients (relative risk, 0.80; p=0.092), stroke (nonfatal and fatal) occurred in 125 losartan-treated patients and 193 atenolol-treated patients (relative risk, 0.66; p<0.001), and myocardial infarction (nonfatal and fatal) occurred in 110 losartan-treated patients and 100 atenolol-treated patients (relative risk, 1.14 [CI, 0.87 to 1.49]; p>0.2). In addition, incident diabetes occurred less often in patients treated with losartan (n = 173) compared to patients treated with atenolol (n = 254) (relative risk, 0.69; p<0.001).

According to the researchers, "the reduction of cardiovascular events with losartan relative to atenolol might be directly related to specific drug-mediated interruption of vasculotoxic effects of angiotensin II, independent of treatment-induced lowering of arterial pressure."

"This clinical benefit in primary prevention of cardiovascular morbidity and mortality in hypertensive patients without clinically evident vascular disease with losartan therapy suggests that its application will improve outcome for hypertensive patients," Dr. Devereux and colleagues conclude.

The manufacturers of losartan, Merck & Co., Inc., supported the study.
Ann Intern Med 2003;139:169-177. "Effects of Losartan or Atenolol in Hypertensive Patients without Clinically Evident Vascular Disease: A Substudy of the LIFE Randomized Trial"

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