Item #6

Diabetic Hypertensives Benefit More From Losartan Than Atenolol

Losartan, the angiotensin-II type-1 receptor antagonist, appears more efficacious than the beta-blocker atenolol among hypertensive diabetics.

"The general message to the practicing physician is that hypertensive diabetic patients with LVH benefit more from losartan than atenolol," declares Dr Lars Hjalmar Lindholm, Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden. He is lead author of the European and North American collaborators in this study as part of the ongoing Losartan Intervention For Endpoint reduction (LIFE) study.

Diabetes mellitus doubles the risk of cardiovascular disease, even in patients with hypertension who are already at high risk because of their high blood pressure. A combination of hypertension and diabetes accounts for a large proportion of cardiovascular morbidity and mortality, the clinicians point out.

Frequency of diabetes mellitus is increasing rapidly worldwide, yet it is still not clear what is the most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes.

The LIFE study, although designed as a trial in patients with hypertension and LVH, was also a correctly randomized study with respect to the pre-specified subgroup of patients with diabetes.

Dr Lindholm and colleagues found that losartan reduced the risk of cardiovascular death, stroke, and myocardial infarction by around 25 percent, the risk of cardiovascular death by 37 percent, and reduced the risk of death from all causes by nearly 40 percent-- 63 in the losartan group and 104 in the atenolol group.

Systolic blood pressure during the trial was not associated with any change in risk of the primary composite endpoint. "Thus, the greater cardiovascular protective effect of losartan than atenolol could result from more pronounced blockade of the detrimental effects of angiotensin II," the clinicians declared.

Losartan was more effective than atenolol in reversing LVH, the clinicians concluded. This is probable because of more complete protection against angiotensin II with losartan, whether generated by the circulating renin-angiotensin system or other mechanisms, especially since angiotensin II is a myocardial growth factor and an independent risk factor for cardiovascular disease. Lancet 2002; 359: 1004-10. Summary:  In those with diabetes, when taking Losartan there was a
*   40% decrease in heart failure
*   39% decrease in death
*   37% decrease in cardiovascular mortality (mostly stroke) compared to those treated with atenolol and had diabetes.

There were similar, but not as spectacular, improvements in those who did not have diabetes.  To date, all evidence suggests that the beneficial effects of ACE inhibitors can be duplicated with ARBs like Losartan.

All patients taking Losartan had significantly decreased adverse effects (side effects).  The class of ARBs seems now to be clearly reasonable to treat hypertension in the face of diabetes, rather than the ACE inhibitors.

Losartan has one unique feature not shared by the other ARBs - it is uricosuric.  This means that uric acid, the material that causes gout, goes out of the kidney at a greater rate, preventing gout.  All patients had significantly decreased blood levels of uric acid.  Not a bad thing when you consider that other drugs, such as thiazides that increase uric acid, might be used in these patients too.

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FACT:  

Since 1980, deaths related to diabetes increased 40 percent while government funding for diabetes research at NIH dropped 20 percent

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