Metabolic modulators: Alternative drug therapy for heart disease

The Charter Bureau

Mang Edgar, a 56-year-old taxi driver from Mandaluyong, has been experiencing chest heaviness for the past six months, particularly while climbing the stairs to his third-floor apartment. His doctor informed him that he had narrowing of the blood vessels supplying his heart muscle (called coronary artery disease), resulting in chest pain and discomfort during physical exertion.

Mang Edgar was happy to hear from his doctor that heart bypass surgery was still unnecessary, and that his chest pain could be readily controlled with so-called hemodymamic anti-anginal drugs. These drugs either decrease the heart muscle’s pumping force (contractility) and speed (heart rate), thus, requiring less oxygen demand from the already impaired blood supply. They also increase the heart muscle’s blood supply by dilating the narrowed blood vessels.

After two weeks of taking these medicines, Mang Edgar informed his doctor that while his chest heaviness had indeed been relieved, he was now suffering from headaches and tiredness, and was unable to perform his marital duties for the first time in his life. His doctor then reduced the dose of his previous medications and added a new drug called a metabolic modulator. To Mang Edgar’s relief, the annoying side-effects of his previous medications disappeared, and he continued to be free of chest pains.

Difference

This experience highlights the growing impact of the metabolic class of drugs on the treatment of heart disease in the Philippines, where coronary artery disease is a leading killer. What makes these drugs different from the rest?

While conventional drugs that act directly on the heart and blood vessels work very well in many instances, they have their share of side-effects, as Mang Edgar’s case demonstrates. They also sometimes work less effectively than both patients and doctors would wish.

Newer, unconventional drugs like the metabolic modulators avoid these side-effects and are also used in combination with conventional drugs to improve efficacy and reduce side-effects. These metabolic modulators work by altering certain chemical processes in the heart muscle cells.

To generate energy and fuel its pumping action, the heart metabolizes, or "burns," two types of energy sources – glucose (from dietary carbohydrates) and fatty acids (from dietary fat). Burning these energy sources requires oxygen from the air we breathe, which of course is delivered to the heart muscle by the circulating blood. Should the oxygen supply be reduced by the narrowing of the arteries in coronary artery disease, the heart will be unable to "burn" glucose and fatty acids. Without any energy source, the heart’s pumping ability will decline and eventually fail, manifesting as chests heaviness and pain, difficulty of breathing, and in severe cases, loss of consciousness and even death.

The conventional definitive treatment for coronary artery disease involves increasing blood and oxygen supply either via bypass surgery or angioplasty (expanding the narrowed artery with a tiny balloon). These procedures are quite expensive and are beyond the reach of many Filipinos.

Side-effects

Medicines that either temporarily enlarge the narrowed artery or decrease the heart’s pumping action are also used, but these drugs do have their side-effects and are not always sufficient to keep the patients symptom-free.

An alternative or a supplement is the use of metabolic modulators, such as the drug trimetazidine (Vastarel). They act by optimizing the metabolism in the heart. Using fatty acids as an energy source requires the use of more oxygen than using glucose.

Trimetazidine and other metabolic modulators avoid "burning" fatty acids as the heart’s energy source. By inhibiting a key substance required for the breakdown of fatty acids (the enzyme designated as 3-KAT), trimetazidine shifts the heart toward the consumption of glucose instead, which requires significantly less oxygen, and in effect, requires less blood supply.

In cases of chronic stable angina, as in Mang Edgar’s case, this shift is very often sufficient to relieve chest pain, and allows the patient to resume normal physical activity.

Perhaps one of the most important features that explains the popularity of metabolic modulators, aside from their proven efficacy, is the rare occurrence of side-effects. Thus, with the development of unconventional, yet effective and well-tolerated drugs like trimetazidine (Vastarel), patients like Mang Edgar can remain symptom-free and enjoy a quality of life which conventional therapy may not be able to offer.

(The author is a former director of the Philippine Heart Center, a past president of the Philippine Heart Association, and currently, the vice president of the Philippine Society of Hypertension and a member of the scientific advisory board of CHARTER – Clinical Hypertension and Atherosclerosis Research on Therapies, Epidemiology and Risk-management – a non-stock, non-profit research foundation which evaluates the impact of risk factors and interventions on heart, lung and other diseases.)