Cardioprotective Agent

Abstract: Background Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied. Objectives The objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines. Search strategy We searched the databases of CENTRAL (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to August 2002) and EMBASE (1980 to August 2002). In addition, we handsearched reference lists and conference proceedings of the International Society for Paediatric Oncology (SIOP) and the American Society of Clinical Oncology (ASCO) (1998 to 2002). Selection criteria Randomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional or placebo therapy in cancer patients (children and adults) receiving anthracyclines. Data collection and analysis Two reviewers independently performed the study selection, quality assessment and data-extraction including adverse effects. Main results We identified RCTs for 5 cardioprotective agents: N-acetylcysteine (1 study; 54 patients), phenetylamines (2 studies; 100 patients), coenzyme Q10 (1 study; 20 patients), combination of vitamin E, vitamin C and N-acetylcysteine (1 study; 14 patients) and dexrazoxane (6 studies; 1013 patients). All studies had methodological limitations. Due to the insufficient number of studies, for the first four mentioned cardioprotective agents pooling of the results was impossible. None of the individual studies showed a cardioprotective effect. The meta-analysis of the dexrazoxane-studies showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (Relative Risk (RR) = 0.28, 95% Confidence Interval (CI) 0.18 to 0.42, P < 0.00001). No statistically significant difference in response rate between the dexrazoxane and control group was found (RR = 0.88, 95% CI 0.77 to 1.01, P = 0.06), but there was some suggestion that patients treated with dexrazoxane might have a lower anti-tumour response rate. Our meta-analysis of survival showed no significant difference between the dexrazoxane and control group. For adverse effects pooling was impossible. However, no important differences in the occurrence of side effects were found. The majority of the patients included in this meta-analysis were adults with advanced breast cancer. Authors' conclusions For cardioprotective agents for which pooling was impossible no high quality evidence was available and therefore, no definitive conclusions can be made about their efficacy. Dexrazoxane prevents heart damage, however there was some suggestion that patients treated with dexrazoxane might have a lower anti-tumour response rate. There was no significant difference in survival between the dexrazoxane and control group. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines. However, for each individual patient clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of a lower response rate.

Abstract: A RAPIDLY growing body of evidence indicates that volatile anesthetics protect myocardium against reversible and irreversible ischemic injury. Identifying the mechanisms by which volatile agents mediate these antiischemic actions is the subject of intense research. This objective has been difficult to accomplish because volatile anesthetics also profoundly affect cardiovascular function. Volatile agents reduce arterial and coronary perfusion pressure, cause dose-related depression of myocardial contractility, produce coronary vasodilation, affect electrophysiologic function, and modify autonomic nervous system activity to varying degrees. Therefore, the antiischemic effects of volatile anesthetics may be mediated, at least in part, by favorable alterations in myocardial oxygen supply–demand relations, preservation of energy-dependent cellular functions, and increased coronary blood flow. However, it seems unlikely that changes in myocardial metabolism and coronary perfusion caused by volatile anesthetics are solely responsible for protection against ischemic damage. Instead, several endogenous signal transduction pathways, acting through the adenosine triphosphate (ATP)–sensitive potassium (KATP) channel and involving the generation of reactive oxygen species (ROS), have been implicated in mediating the antiischemic actions of volatile anesthetics. The experimental and clinical findings documenting the phenomenon of volatile anesthetic preconditioning against ischemic injury of myocardium are evaluated. Recent findings in vitro and in vivo that seek to define the intracellular mechanisms responsible for these beneficial actions are also summarized.

Abstract: Brief myocardial ischemia not only evokes a local cardioprotective or “preconditioning” effect but also can render remote myocardium resistant to sustained ischemia. We propose the following hypoth...