An important option in coronary artery disease

Despite advances in the treatment of heart ailments, questions still bother experts on the outcome of various treatment interventions. Why is the annual death among post-bypass cases with high blood pressure, diabetes, obesity and high cholesterol levels higher compared to those patients without these risk factors? Why is the frequency of significant occlusive coronary artery disease almost only 50 percent among patients with typical chest discomfort (angina), and/or positive treadmill exercise test?

Blood is distributed to cells and tissues via a microcirculation that accounts for 90 percent of heart muscle blood flow. Imagine that the heart circulation network of blood vessels is similar to a road network consisting of national highways leading to provincial roads to single-lane barrio passages terminating in driveways to each house. The damaged asphalt road simulates the innermost layer of the blood vessels (endothelium).

Segmental narrowing of blood vessels supplying the heart muscle has been perceived to be the cause of heart attacks or angina. To bypass the blocked segment, an overpass is created (heart bypass graft surgery) or tunnels are established (balloon angioplasty with stent). However, in most cases, despite these interventions, heart attack cannot be prevented since blood clots can completely block even minimally narrowed blood vessels due to endothelial damage (imagine potholes and humps causing traffic jams). Furthermore, mere restoration of blood flow at the larger blood vessels may still leave smaller ones blocked.

This microvascular circulation abnormalities affect cell nourishment. With endothelial damage smallest blood vessels (capillaries) deprived of adequate blood flow depend on fatty acids (derived from fats) for food. However, conversion of fatty acids to energy for the cells require more oxygen than energy derived from glucose. Thus despite surgical or invasive interventional procedures, unless cell uptake of glucose accompanies blood flow restoration, a functional heart muscle may not be achieved.

As supply is diminished, inadequate blood flow may be balanced with demand if demand is reduced. Rest or reduced activity can provide symptom relief. A beta-blocker medication reduces demand to provide angina relief. However, new onset diabetes and asthmatic attacks can develop following beta-blocker use.

Another drug, nitrates (isosorbide or nitroglycerine tablet or patch), relaxes blood vessel wall to increase acutely the narrowed vessel, thus relieving angina. However, chronic intake of nitrates, particularly after a previous heart attack, can produce "nitrate tolerance" or a resistance to the nitrate benefit. In fact, a Japanese study showed increased sudden death or repeat heart attacks following chronic nitrate use among patients with previous heart attacks.

In a situation where oxygen supply is already compromised by the diminished blood supply, an agent that facilitates cells to derive energy from glucose more than from fatty acids, thus needing less oxygen, provide improved quality of life, improved cell survival after a heart attack, increased glucose uptake of cells is currently available in a twice daily dose of 35 mg trimetazidine (TMZ). Given before and after revascularization procedures, TMZ on positron emission tomography scan (PET) to indicate cell glucose uptake and dobutamine stress echo also demonstrates improved heart muscle function. Our local study that was subsequently confirmed by a multi-center larger patient study in Europe showed improved cell survival with reduced mortality after a heart attack.

A paradigm shift in CAD management is the use of TMZ to relieve angina, improve survival after a heart attack among those ineligible for thrombolysis (clot-dissolving treatment), improved heart muscle function after surgical intervention. More importantly, TMZ has no side effects, does not produce new onset diabetes unlike beta-blockers, nor produce tolerance unlike nitrates that can lead to adverse events. Anginal relief is likewise similar to other anti-anginal agents.