Number 23, 2004
Hibernation preconditioning

Metabolic interventions for acute coronary syndromes?

Back to the Summary

Frans C. Visser
Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands
Correspondence: Professor Frans Visser, Department of Cardiology, Academic Hospital Vrije Universiteit, De Boelalaan 1117, 1081 HV Amsterdam, The Netherlands.
Tel: 31 20 444 44 44; fax: 31 20 444 24 46; e-mail: fc.visser@azvu.nl

Acute coronary syndromes (ACS) represent a major cause of morbidity and mortality for patients with cardiovascular disease. Indeed, nowadays more patients are admitted to the coronary care unit with an acute coronary syndrome than with acute myocardial infarction or heart failure. It is not a benign disease: in the main clinical article of this issue of Heart and Metabolism, Malhotra et al demonstrate that early mortality (14 days) may range between 0.36% and 5.8%, 1-year mortality between 6% and 11%, and 4-year mortality may be as high as 47%. Moreover, having patients with an acute coronary syndrome has also economic consequences as over the years there is a clear tendency for a more aggressive therapeutic approach with PCI and bypass surgery. Also, the increasing use of expensive glycoprotein IIb/IIIa receptor inhibitors adds to the costs. Finally, it is more and more common to dismiss ‘low-risk’, complaint-free patients with aspirin, clopidogrel, ß-blockers, statins, and angiotensin converting enzyme (ACE)-inhibitors, some of which may be given life-long.
Management of the acute coronary syndrome patient is getting to be a complicated business, both from the diagnostic and from the therapeutic point of view. For medical therapy the use of heparin, low-molecular weight-heparin, clopidogrel, glycoprotein IIb/IIIa receptor inhibitors, iv nitrates, ß-blockers, calcium antagonists, statins, and ACE-inhibitors has to be considered in an individual patient. On top of that, quite a few patients require bypass surgery or PCI. Clearly, risk stratification is needed on how to treat patients with which drug, for how long or which intervention is warranted. However in risk stratification, things are also getting complicated. We now have risk factors such as age, gender, diabetes mellitus, and previous coronary events/known coronary artery disease, and current use of antithrombotics to take into consideration. Moreover, there are powerful diagnostic techniques like the ECG, troponine, classical cardiac enzymes, BNP levels, creatinine clearance, inflammation markers, LV function data by echocardiography, SPECT and MRI, perfusion and metabolic imaging data, and coronary angiograms to consider.
In this wilderness of diagnostic and therapeutic possibilities for patients presenting with an ACS, this issue of Heart and Metabolism is extremely helpful. In the ‘main clinical article’ and in the ‘new therapeutic approaches’ sections Malhotra et al and Eberli discuss how patients may be treated. The central theme of the authors is risk stratification, and patients should be treated accordingly. Both articles offer simple and easy-to-use schemes, based on the American and European guidelines on how to approach these kinds of patients, both from a diagnostic and therapeutic point of view. I would recommend that every reader study these articles thoroughly and advise them to pass on this issue after reading to fellows-in-training. Of course, simplified schemes do not tell the whole story: every patient deserves an individual approach in which all the available clinical data need to be taken into account. Nevertheless, these articles are a good starting point.
Another interesting point that is highlighted in this issue of Heart and Metabolism is the ‘metabolic therapeutic approach’ to patients with an acute coronary syndrome. In the ‘basic article’ by Noga et al and in the ‘refresher corner’ by Stanley the metabolic changes in ACS are discussed. At the end of the articles the potential pharmacological strategies are summarized, aiming to reduce fatty acid oxidation and increasing glucose oxidation. The major role of glucose and fatty acid changes in patients (and not only in animal experiments), is highlighted in the 'imaging' article of Hambye and Franken. They also advocate the use of metabolic imaging for further risk stratification. Eberli in the ‘new therapeutic approaches’ section pleads for the use of metabolic interventions with glucose-insulin-potassium (GIK) and fatty acid oxidation inhibitors in ACS. The case report by Szwed shows that the fatty acid oxidation inhibitor trimetazidine reduces the frequency of ischemic episodes in a patient with previous unstable angina. Finally, the beneficial clinical effects of trimetazidine in patients undergoing revascularization are discussed in the ‘Focus on Vastarel’ article by Meurin and Henane. After all, bypass surgery is a global acute coronary event.
It is clear that all authors are enthusiastic about the concept of a metabolic intervention in acute coronary syndromes, as there is a sound rationale. But in this world of evidence-based medicine we are lacking solid clinical data. There are limited data about the use of GIK in acute myocardial infarction, there are no data in ACS. The same applies to the use of fatty acid oxidation inhibitors. We do not know if these pharmacological agents reduce hard and soft end points during follow-up, or lower the risk profile of a patient. Therefore, we are not yet ready to apply these agents into clinical practice. Nevertheless, the concept of metabolic interventions in ACS is very challenging and clinical trials should be designed to prove this. Enjoy reading.?

Back to the Summary