Chemical Market Reporter - RAMIPRIL.(American Home Products receives FDA approval)(Brief Article)
In the Heart Outcomes Prevention Evaluation (HOPE) study, 9,541 patients with cardiovascular disease or diabetes, plus one other cardiovascular risk factor, were randomly assigned to receive, in double-blind fashion, 400 IU/day of vitamin E (RRR-alpha-tocopheryl acetate) or placebo, and either an angiotensin-converting-enzyme inhibitor (ramipril) or placebo, for a mean of 4.5 years. Results of the study showed that ramipril was beneficial, but vitamin E was not.
Related Results
King and Dura give old drugs new life in the marketplace
Safety, efficacy shown for metoprolol, ramipril.(Clinical Rounds)
King Pharmaceuticals to license Skyepharma’s delivery technology.
Groundbreaking Discovery of the Benefits of Anti-hypertensives Beyond Blood P…
King Pharmaceuticals Announces ALTACE Tablets Launch
At the end of the study, 6,786 patients agreed to enter a continuation phase, in which all patients received ramipril, and 3,994 patients were randomly assigned to receive 400 IU/day of vitamin E or placebo for an additional 2.6 years, producing a total study duration of 7.1 years. At the end of the first part of the study, the incidences of heart failure events and hospitalizations for heart failure were higher in the vitamin E group than in the placebo group, but the differences were of only borderline statistical significance. The results from the continuation phase, when combined with the original results, did achieve statistical significance: heart failure events occurred in 14.7% of those using vitamin, compared with 12.6% of those using placebo (16.7% increase) and hospitalizations for heart failure occurred in 5.8% and 4.2% of patients, respectively (38.1% increase).
Comment: Vitamin E has a long and controversial history as a potential treatment for heart disease. While some large-scale clinical trials have found vitamin E to be beneficial, the majority of studies have found little or no effect of vitamin E. The HOPE trial is the first to suggest that vitamin E actually increases the risk of certain types of heart disease.
All of the studies of vitamin E supplementation for heart-disease prevention have used alpha-tocopherol, whereas the vitamin E in food contains four different isomers: alpha-, beta-, gamma-, and delta-tocopherol. An increasing body of evidence indicates that gamma-tocopherol has a strong cardioprotective effect. Moreover, supplementing with large doses of alpha-tocopherol results in a decline in serum concentrations of gamma-tocopherol. It is possible, therefore, that the positive effects of alpha-tocopherol are negated by a reduction in gamma-tocopherol levels. That possibility is supported by epidemiological studies indicating that vitamin E from food protects against heart disease, whereas vitamin E from supplements (e.g., alpha-tocopherol alone) does not. Future vitamin E studies should use “mixed tocopherols” that contain the four vitamin E isomers in proportions that are similar to those found in the diet.
Zoler ML. Supplemental vitamin E linked to heart failure. Fam Pract News 2003(October 1):28.
COPYRIGHT 2004 The Townsend Letter Group
COPYRIGHT 2004 Gale Group
