Drug Losartan Beneficial Throughout Five-Year Study Period
Aug 12, 2003
Physician-scientists at Weill Cornell Medical College and NewYork-Presbyterian Hospital have demonstrated that, among hypertensive patients with electrocardiographic evidence of a type of enlarged heart condition called left ventricular hypertrophy (LVH), the drug Losartan is more likely to reduce the severity of their condition than the drug Atenolol. Losartan's benefits were demonstrated throughout the five-year study period, irrespective of a number of factors, including the severity of the condition. LVH, a condition in which the heart's lower-left chamber (left ventricle) has grown thicker, is a risk factor associated with heart failure, myocardial infarction, and cardiovascular death.
The study, published in the August 12 issue of Circulation, and available online, confirms earlier findings of the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension multicenter study of 9,193 hypertensive patients. The research shows that Losartan-based therapy was more effective at reducing LVH than the beta-blocker Atenolol, according to two electrocardiographic-based measurement standards: Sokolow-Lyon voltage and Cornell voltage-duration (Lancet 2002).
The current double-blind and randomized study, which uses patient data from the LIFE study, additionally finds that (1) Losartan compares favorably at six months, and at one-year intervals through five years; (2) the drug is effective irrespective of the severity of LVH and hypertension, or changes in blood pressure due to treatment; and (3) the drug is effective irrespective of patient gender, age, ethnicity, and presence of diabetes.
"By the first six months of treatment, patients treated with Losartan had a nearly three times greater reduction in LVH than those treated with Atenolol. We now know that these benefits continue through five years, and irrespective of a variety of factors," said Dr. Peter M. Okin, the study's principal investigator; Professor of Medicine at Weill Cornell Medical College; and Attending Physician at NewYork-Presbyterian Hospital.
Additionally, the current study suggests that Losartan has a direct effect on reducing the degree of LVH, independent of the drug's effect on reducing blood pressure. "This is suggested by the finding that Losartan treatment resulted in greater regression of LVH than Atenolol—even though the two drugs produced almost identical reductions in both systolic and diastolic blood pressure," said Dr. Okin. "Further supporting this contention are the statistical analyses in which we adjusted for any possible differences between the treatment groups and still found a much greater reduction in LVH with Losartan. However, further study is required to assess this issue."
Left ventricular hypertrophy (LVH) is a response to an underlying cardiovascular condition, most commonly, high blood pressure. Other underlying conditions include valvular heart disease and coronary heart disease. The prevalence of LVH in patients with moderate-to-severe hypertension is approximately 20 to 25 percent.
The current study was co-authored by Dr. Richard B. Devereux, Professor of Medicine at Weill Cornell Medical College and Attending Physician at NewYork-Presbyterian Hospital. Dr. Devereux was also co-author of the original LIFE study published in Lancet.
Cornell product criteria were developed by Dr. Okin and others at NewYork Weill Cornell Medical Center, and have been demonstrated to be the most sensitive of standard ECG criteria for the detection of anatomic hypertrophy. Cornell product criteria were the predominant ECG criteria used to recruit patients in the LIFE study.
Losartan, an angiotensin receptor blocker (ARB), has been approved by the FDA for the treatment of hypertension and for reducing the risk of stroke in patients with hypertension. There has not yet been an application to the FDA to seek approval to treat and regress hypertrophy. Losartan is manufactured by Merck & Co. of New Jersey.
The study was funded by a grant from Merck & Co.