Coronary artery disease is the single most important killer of Canadians. Despite major
advances in therapy, there is still a significant proportion of patients identified with the
disease who die of it because current treatment approaches cannot effectively palliate their
condition. A new treatment modality called therapeutic angiogenesis has appeared on the
clinical research scene during the last five years; this approach recreates the natural
processes of new blood vessel formation that is observed during growth and development in
every human being. It is an extremely potent and promising modality, but so far the results
of clinical trials in patients have been equivocal.
One reason for the limited efficacy observed thus far with therapeutic angiogenesis may rest
in that factors produced by the lining of the coronary arteries themselves are essential for
angiogenic substances to take effect in the heart muscle of patients with severe coronary
artery disease. These same patients, however, virtually all have, as a result of their
disease, marked dysfunction of their coronaries and therefore fail to produce these factors
in adequate quantities. This hypothesis has been verified with extensive animal data by the
investigators of this research, where a swine model of coronary disease was shown to severely
inhibit the action of angiogenic growth factors. If one wants angiogenesis to work, a means
of improving the function of the coronary lining of patients with severe ischemic heart
disease must be identified and its effects evaluated in order to allow for angiogenic
substances to exert their action towards successful revascularization of the heart muscle.
An amino acid called L-arginine has repeatedly been shown to markedly improve function of the
coronary artery lining in patients with ischemic heart disease when administered regularly
over a period of several months. This research will therefore test, in the form of a
randomized clinical trial, whether this concomitant approach can make angiogenesis effective
in patients with advanced coronary disease, by allowing for the action of growth factors to
take place in the heart. If this approach is successful, as is anticipated, angiogenesis will
constitute an effective modality for the treatment of coronary artery disease, not only in
patients with advanced, severe involvement unamenable to any other form of cardiac therapy
such as coronary artery bypass grafting, but even perhaps in all patients with coronary
artery disease in need of revascularization. The goal of this investigation towards the
making of a new, revolutionary, safe and efficacious modality for the treatment of the number
one killer disease of Canadians is in complete agreement with the primary objective of the
Heart and Stroke Foundation of Canada.