Colchicine Versus Beta-blockers, Angiotensin-converting Enzyme Inhibitors, and Statins for Prevention of Chemotherapy-Induced Cardiomyopathy

The 2021 European Society of Cardiology (ESC) guidelines recommend that the treatment with angiotensin-converting enzyme inhibitors (ACEi) and a beta-blocker (preferably carvedilol) should be considered in cancer patients developing left ventricle systolic dysfunction, defined as a 10% or more decrease in left ventricular ejection fraction (LVEF) from baseline value or a value lower than 50%, during anthracycline chemotherapy. This statement has a class of recommendation of II with a level of evidence B, which means that the weight of evidence/opinion is in favor of the usefulness of these treatments. The statement recommends starting the dual treatment after echocardiographic evidence of cardiac affection. Therefore, whether pre-treatment with these dual cardio-protective agents will protect the patient's heart from the toxic effects of the chemotherapeutic intervention is unclear.

Additionally, The 2022 ACC/AHA/HFSA American guidelines recommend that in asymptomatic patients with cancer therapy-related cardiomyopathy (ejection fraction<50%), angiotensin-receptor blocker (ARBs)and beta-blockers are reasonable to prevent progression to heart failure and improve cardiac function. The statement also recommends starting the dual treatment after echocardiographic evidence of cardiac affection. However, these guidelines state that in patients at risk of cancer therapy-related cardiomyopathy, initiation of beta blockers and ACEi/ARB for the primary prevention of drug-induced cardiomyopathy is of uncertain benefit and further clinical research is an unmet need. Accordingly, the effectiveness of preemptive use of ACEi-ARB and/or selected beta-blockers (such as carvedilol and nebivolol) in reducing the risk of cancer therapy-related cardiomyopathy has been investigated in a number of small clinical trials, with conflicting findings. Additionally, statins have pleiotropic therapeutic effects that range from endothelial stabilization to suppression of inflammation. However, its role in decreasing disease morbidity (repeated hospitalization) in established chronic heart failure is also uncertain.

On the other hand, colchicine is an immunomodulator that accumulates in the white blood cells and affects them in a variety of ways including decreasing motility, mobilization, and adhesion. Generally, colchicine appears to inhibit multiple proinflammatory mechanisms, while enabling increased levels of anti-inflammatory mediators. In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received a placebo. Accordingly, colchicine can reduce the risk of cardiovascular events in patients with chronic coronary artery disease, but its efficacy in improving the functional status in patients with established chronic heart failure is also uncertain. While the use of this immunomodulatory agent in established heart failure is uncertain, its effectiveness in the prophylactic reduction of chemotherapy-induced cardiomyopathy in patients with normal pre-treatment ejection fraction has not been investigated.

Accordingly, 150 enrolled cancer patients who are candidates for guideline-directed anthracycline-based chemotherapy with or without the anti-HER2 trastuzumab at the time of presentation, will undergo the following:

• General and Local cardiac examination.
• CBC.
• Chemistry Panel including KFTs, LFTs.
• Serum electrolytes levels.
• Baseline resting surface 12 leads ECG followed by serial recording (monthly for a total of 6 months).
• Baseline Echocardiography followed by serial imaging every 2 months for a total of 6 months.
• Baseline serum BNP test/NT-proBNP followed by serial testing every 2 months for a total of 6 months.