Department of Clinical and Molecular Medicine, Sapienza University of Rome, Ospedale Sant'Andrea, Rome, Italy.
Int J Cardiol. 2013 Sep 10;167(6):2421-9. doi: 10.1016/j.ijcard.2013.01.052. Epub 2013 Feb 12.
We aimed to revise the increasingly accruing data about the association between anti-tyrosinkinase, "targeted" cancer drugs and the development of arterial thrombotic events or acute coronary syndromes. Further insights into the involved pathophysiologic mechanisms, and into the clinical implications are overviewed. Antiangiogenesis has become a mainstream of cancer therapy, leading to development of a specific class of drugs. Besides, a "wider" angiogenesis network made up of several growth factors, can be recognized as target of a higher number of compounds. Their widespread use has been progressively favored over conventional chemotherapy, because of their better safety/efficacy profile, even allowing a prolonged administration. However, there is a growing awareness of an association between these useful drugs and serious cardiovascular side effects including myocardial infarction, stroke, heart failure and cardiovascular death, in addition to the known relation with the most frequent hypertension onset. Observational studies indeed report that combined cardiovascular events may reach figures of 20-40%, and, for their management, several monitoring, diagnostic and therapeutic regimens have been suggested. On the basis of the available data we recommend an active screening program for acute coronary syndromes in the "at risk" period, immediately after the beginning of the "targeted" drug therapy, and during the whole administration time. Likewise, a mandatory cardiological specialistic evaluation is warranted to plan a schedule of follow-up evaluations for diagnostics, including ECG, echocardiogram, and multimarker evaluation. An appropriate treatment with antiplatelet or anticoagulant drugs, endothelial protective agents or cardiovascular interventions is similarly advised.
我们旨在修订与抗酪氨酸激酶、“靶向”癌症药物与动脉血栓事件或急性冠状动脉综合征发展之间关联的不断增加的数据。进一步深入了解相关的病理生理机制和临床意义。抗血管生成已成为癌症治疗的主流,导致了一类特定药物的发展。此外,由几种生长因子组成的“更广泛”的血管生成网络,可被视为更多化合物的靶点。由于其更好的安全性/疗效特征,甚至允许延长给药时间,它们的广泛使用逐渐优于传统化疗。然而,人们越来越意识到这些有用药物与严重心血管副作用之间的关联,包括心肌梗死、中风、心力衰竭和心血管死亡,除了已知与最常见的高血压发病有关。观察性研究确实报告称,联合心血管事件的发生率可能达到 20-40%,并且为了进行管理,已经提出了几种监测、诊断和治疗方案。根据现有数据,我们建议在“靶向”药物治疗开始后和整个治疗期间,对“高危”时期的急性冠状动脉综合征进行积极的筛查计划。同样,有必要进行强制性的心脏病学专门评估,以计划后续评估的随访计划,包括心电图、超声心动图和多标志物评估。同样建议使用抗血小板或抗凝药物、内皮保护剂或心血管介入治疗进行适当的治疗。