Cozaar (Losartan) Lowered Risk Of Total Mortality In Patients With Diabetes By 39% Versus Atenolol

Treatment with losartan resulted in a 24 per cent reduction in the primary composite endpoint of cardiovascular death, stroke and heart attack. 

In a pre-specified subgroup of hypertensive patients with diabetes, Cozaar® (losartan) was significantly more effective in reducing the combined risk of cardiovascular death, heart attack and stroke, according to an analysis of the landmark LIFE trial. 

These results were presented Thursday at the joint International Society of Hypertension/ European Society of Hypertension meeting in Prague, Czech Republic. This finding is consistent with the beneficial effects of losartan in reducing the combined cardiovascular morbidity and mortality demonstrated in the overall LIFE study population.

"Patients with diabetes are an important patient group, as they have double the risk of cardiovascular disease, and this risk is further increased by hypertension," said Lars H. Lindholm, M.D., principal investigator of the diabetes subgroup analysis, and professor, Umeå University Hospital, Umeå, Sweden. "Losartan has now been shown to be superior in reducing the combined risk of cardiovascular disease and death in diabetic patients in the LIFE trial."

"The observation that losartan has much greater impact on reducing stroke and the death rate overall obliges us to rethink the way we treat patients with diabetes who have high blood pressure in Canada," said Dr. John Floras, President of the Canadian Hypertension Society, staff cardiologist and Director of Research, Toronto's University Health Network and Mount Sinai Hospital Division of cardiology.

Findings from the LIFE (Losartan Intervention For Endpoint reduction in hypertension) substudy in 1195 hypertensive patients with diabetes showed that treatment with losartan resulted in a 24 per cent reduction in the primary composite endpoint of cardiovascular death, stroke and heart attack compared to the beta-blocker atenolol (p=0.03). Blood pressure and pulse pressure reductions were similar with both therapies. In addition, losartan significantly reduced the risk of cardiovascular death by 37 per cent (p=0.03) and total mortality by 39 per cent (p=.002).

"A 39 per cent reduction in total mortality with losartan is an important observation given that the observed reduction is versus an established antihypertensive, atenolol. The LIFE study showed that it matters how we lower blood pressure," Dr. Lindholm said.

In comparison, in the 9,193-patient LIFE study as a whole, losartan significantly reduced the combined risk of cardiovascular death, heart attack and stroke -- the primary endpoint of the study -- in patients with hypertension and left ventricular hypertrophy (LVH) by 13 per cent compared to atenolol (p=0.021). In addition, losartan reduced the risk of stroke by 25 per cent (p=0.001). These results occurred even though blood pressure was reduced to a similar level in both the losartan and atenolol treatment groups.

"In another pre-specified subgroup of patients with isolated systolic hypertension, the findings on stroke with losartan versus atenolol were consistent with those seen in the overall study population," said Sverre Kjeldsen, M.D., Ph.D., a LIFE Steering Committee member, and adjunct professor of medicine, University of Michigan, and chief physician of Cardiology, Ullevaal University Hospital, Oslo, Norway. "The data on this important group of patients are scheduled for presentation later this year. It is widely accepted that elevated systolic blood pressure is an even stronger risk factor for cardiovascular events than diastolic blood pressure."

Diabetic study patients were 55-80 years old with previously treated or untreated hypertension and signs of LVH as measured by electrocardiogram (ECG). Patients were randomized to losartan or atenolol after one to two weeks of placebo if trough sitting blood pressures were 160 to 200 mmHg systolic and 95 to 115 mmHg diastolic. Mean follow-up time was 4.7 years with patients having regular visits and upward titration of medication to reach a blood pressure goal of less than 140/90 mmHg.

In the overall LIFE trial, the results of the primary endpoint were consistent across 23 of the 24 study subgroups examined. However, additional analyses of the treatment effect by ethnicity suggested that black patients treated with atenolol were at lower risk of experiencing cardiovascular death and disease compared to patients treated with losartan.

Did You Know?

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