(Circulation. 2001;104:115.)
© 2001 American Heart Association, Inc.
Current Perspectives |
Angiogenesis Therapy
Amidst the Hype, the Neglected Potential for Serious Side Effects
From the Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington DC (S.E.E., R.K., S.F.) and Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass (H.F.D.).
Correspondence to Stephen E. Epstein, MD, Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, 110 Irving St NW, Suite 4B-1, Washington, DC 20010.
Key Words: angiogenesis • heart disease • cells • genes • growth substances
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Introduction |
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Although essentially unknown as a therapeutic concept as recently as a decade ago, it is difficult now to open a cardiology journal, attend a cardiology meeting, or scan a newspaper without being caught up in the excitement generated by the thought that angiogenesis therapy may soon have a major impact on the treatment of patients with atherosclerotic lesions obstructing arteries that supply the myocardium or legs. Potent therapeutic interventions, however, are rarely free of at least the potential for causing harmful effects. Angiogenesis therapy is no exception. Despite this and despite the fact that the only reasonably powered, randomized, double-blind clinical studies to date have failed to demonstrate primary end-point efficacy,1 thoughtful consideration of the serious side effects that might accompany any therapeutic benefit has been largely missing from scientific communications.
For the lay media, a switch from this unbounded enthusiasm
to profound skepticism occurred recently after a report of the tragic
death of a young man caused by injection of large amounts of an
adenoviral vector into the hepatic artery (unrelated to angiogenesis
therapy).2 For the scientific
community, however, there has been a general lack of in-depth
discussion of the potential dangers inherent in angiogenesis
interventions. Such a discussion is appropriate not only because of the
event cited above but also because considerable mechanistic data are
available that actually permit us to identify specific side effects
that we might anticipate as potential complications of angiogenesis
therapy. The following therefore is a discussion of potential
complications based predominantly on our
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