Treatment strategies to avoid heart attack complications

(Conclusion)

Standard of care in heart attack patients includes administration of agents which prevent platelet activation and aggregation (such as aspirin and clopidogrel) and which slow down further clot formation (such as heparins).

Antiplatelets and anticoagulants assist the body’s innate clot lysis system and more importantly decrease the chance of dying from a heart attack or suffering a second one. Cholesterol-lowering agents, particularly the statins, likewise help reduce cholesterol deposits in the blood vessel wall, thus damping the major trigger for blood clots and preventing further heart attacks.

Another proven treatment in AMI patients are beta-blockers which slow heart rate, lower blood pressure, and decrease the contraction force of the heart muscle leading to reduced myocardial oxygen demand and ultimately less complications. Unfortunately, beta-blockers are contraindicated in asthmatic patients such as Ernesto P. Nitrates, which preferentially dilate the veins and coronary arteries and thus help increase myocardial blood supply, are used to make heart attack patients feel better. However, prolonged use often leads to nitrate tolerance, and large clinical trials failed to show improved survival or reduced risk of repeat MI with the use of nitrates. More recently, studies have demonstrated cardioprotective benefits of another class of vasodilators called angiotensin converting enzyme (ACE) inhibitors in the setting of a heart attack, and hence their routine use in AMI patients is now recommended as well in clinical guidelines.

However, improving myocardial oxygen supply and reducing oxygen demand with so-called hemodynamic manipulation can only go so far, especially in the setting of acute heart attack wherein the culprit artery remains severely narrowed. Fortunately, in our local setting, a different but complementary approach exists to help the oxygen-starved (ischemic) myocardium become more efficient in utilizing the limited oxygen supply.

The problem with myocardial ischemia is that it’s equated with just structural obstruction and reduction of flow through the coronary arteries and therefore is related to inadequate delivery of oxygen and energy sources. It is more than that! It has something to do with more efficient utilization of energy sources in the phase of limited supply of oxygen.

When oxygen is deficient, the effective process of energy production using the fatty acids is effectively shut down. The cells and tissues have to shift to a process which utilizes less oxygen to maintain production of needed amounts of energy known as ATP. This is known as metabolic shift.

This treatment approach is based on metabolic manipulation, which switches the fuels used for energy production from the more oxygen-wasting fatty acids to the more oxygen-sparing glucose. Trimetazidine is one such agent which induces this "metabolic shift," thus permitting the heart cells to manufacture more energy molecules called adenosine triphosphate (ATP) with less oxygen.

Many clinical trials involving over a thousand patients with coronary artery disease have shown that trimetazidine reduces anginal symptoms as well as objective evidence of myocardial ischemia. With regards to heart attack, a study done in Europe enrolling 19,725 AMI patients demonstrated that, among those patients who did NOT receive thrombolysis, treatment with trimetazidine led to improved outcomes in 35 days with less cardiac deaths and complications from heart attack. Likewise, a study conducted locally involving 51 AMI patients who did not receive thrombolysis showed more myocardial salvage after two months of trimetazidine therapy. These findings are especially encouraging and relevant for many heart attack patients in local practice since the majority of them will not receive thrombolysis (or even less likely PTCA/ICS) in the acute setting as mentioned earlier.

In summary, various intervention or therapeutic agents are designed to improve blood flow (nitroglycerine/isosorbide, thrombolytic therapy, PTCA, CABG) while some are designed to reduce demand for oxygen by the heart (beta-blocker and calcium antagonists). Trimetazidine works by enhancing the metabolic shift.

In the final analysis, combined therapy using antiplatelets/anticoagulants, statins, hemodynamic agents (especially ACE-inhibitors), and metabolic agents provide the best chance for "weathering the storm" or surviving a heart attack with minimal complications.