American Heart Journal
Volume 158, Issue 1 , Page e13, July 2009

Response

Merck Research Laboratories, Rahway, NJ

Article Outline

 

The study cited by Masterjohn provides indirect evidence that several factors, possibly including cholesteryl ester transfer protien (CETP) may mediate vitamin E exchange in vitro.1 However, prior investigations indicate a specific role for phospholipid transfer protein and not CETP in facilitating the transfer of vitamin E between plasma lipoproteins both in vivo and in vitro.2, 3, 4 To the best of our knowledge, there are no clinical data indicating a definitive role for CETP in vitamin E exchange. Nevertheless, it is not clear whether alterations in vitamin E exchange would have downstream effects on atherosclerosis. Several large, randomized clinical trials have failed to show a cardiovascular benefit of vitamin E supplementation.5

Treatment with torcetrapib was associated with an increase in blood pressure, alterations in serum electrolytes, and an increase in circulating aldosterone levels.6 These effects appear to be compound-specific and unrelated to the mechanism of CETP inhibition.7, 8 It is reassuring that no alterations in blood pressure, serum electrolytes, and aldosterone levels were observed in the phase II study with anacetrapib.9 A study to assess long-term efficacy and safety of anacetrapib in patients with coronary heart disease is currently in progress (clinical trials.gov NCT00685776). The safety information provided by this trial will determine whether or not to initiate a phase III outcome trial with anacetrapib. Ultimately, it is only by conducting such an outcome trial that the true efficacy and safety of anacetrapib will emerge.

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References 

  1. Hacquebard M, Vandenbranden M, Malaisse WJ, et al. Vitamin E transfer from lipid emulsions to plasma lipoproteins: mediation by multiple mechanisms. Lipids. 2008;43:663–671
  2. Granot E, Tamir I, Deckelbaum RJ. Neutral lipid transfer protein does not regulate alpha-tocopherol transfer between human plasma lipoproteins. Lipids. 1988;23:17–21
  3. Desrumaux C, Deckert V, Athias A, et al. Plasma phospholipid transfer protein prevents vascular endothelium dysfunction by delivering alpha-tocopherol to endothelial cells. FASEB J. 1999;13:883–892
  4. Jiang XC, Tall AR, Qin S, et al. Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E. J Biol Chem. 2002;277:31850–31856
  5. Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297:842–857
  6. Barter PJ, Caulfield M, Eriksson M, et al. for the ILLUMINATE Investigators Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–2122
  7. Krishna R, Anderson MS, Bergman AJ, et al. Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies. Lancet. 2007;370:1907–1914
  8. Forrest MJ, Bloomfield D, Briscoe RJ, et al. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol. 2008;154:1465–1473
  9. Bloomfield D, Carlson GL, Sapre A, et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J. 2009;157:352–360

PII: S0002-8703(09)00359-7

doi:10.1016/j.ahj.2009.05.005

Refers to article:

  • Effect of cholesteryl ester transfer protein inhibitor on vitamin E transport should be studied

    Christopher Masterjohn
    American Heart Journal July 2009 (Vol. 158, Issue 1, Page e11)

American Heart Journal
Volume 158, Issue 1 , Page e13, July 2009

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