Statins may help prevent anthracycline cardiotoxicity in chemotherapy
One of the key late-breaking clinical trials at ACC.23 was STOP-CA, which showed the use of use of statins in cancer chemotherapy treatments can help prevent cardiotoxicity from anthracycline agents. There has been an expansion of cardio-oncology programs to monitor cardiac toxicity in patients during treatment with these agents in attempts to prevent post-chemotherapy heart failure. This study showed that the simple use of stains may offer a new drug for added cardio-protective effects.
One drug is already approved by the FDA to reduce anthracycline-related cardiotoxicity, dexrazoxane, but it is infrequently used due to potential secondary side effects. Statins, on the other hand, are associated with very few side effects in most patients.
Trial co-principal investigators Marielle Scherrer-Crosbie, MD, director of echocardiography at both the Hospital of the University of Pennsylvania and the Penn Cardiovascular Institute, and Tomas Neilan, MD, MPH, director of the cardio-oncology program and co-director of the cardiac MR/PET/CT program at Massachusetts General Hospital, explained the details of the STOP-CA clinical trial in the video above and article below.
"I think our study shows patients with lymphoma treated with anthracyclines and atorvastatin were protected, it decreased the rate of cardiac dysfunction and, if we are considering patients at the higher risk of cardiac dysfunction with higher doses of anthracyclines are older or obese, this study is a significant argument to prescribe atorvastatin to these patients," Scherrer-Crosbie explained.
The STOP-CA trial focused on 300 patients undergoing chemotherapy for lymphoma who were randomized to atorvastatin or a placebo for 12 months to test if there was any cardioprotective effects. Overall, patients experiencing a decline in left ventricle ejection fraction (LVEF) of 10% or more were seen in 22% in the placebo arm, and in just 9% of the atorvastatin arm. A LVEF reduction of 5% or more was also more common among patients treated with atorvastatin.
"That is a significant difference," Scherrer-Crosbie explained. "In other words, the patients in the placebo group had nearly a three-fold increase risk of occurrence of cardiac dysfunction compared to the patients in the atorvastatin group."
Some subgroups also benefited more than others in the study.
"Women, older patients [median age of 52], patients with higher anthracycline doses [at or above 250 mg/m2] and patients who were obese all had significant benefits from statins," Scherrer-Crosbie said.
This was a relatively small sample size and the the study PIs said follow-up research will still be required.
Patient selection for atorvastatin cardio-protective use in anthracycline chemo patients
Neilan said he has gotten a lot of questions from people about the trial and which patients are the best candidates for primary prophylaxis using atorvastatin.
"If a patient is a 24-year-old diagnosed with non-Hodgkin lymphoma and is otherwise healthy, they probably will not see a benefit from atorvastatin. However, if the individual is older and maybe a little overweight, and scheduled to get higher anthracycline doses, and perhaps they are female, they are much more likely to derive a benefit from atorvastatin," Neilan explained.
He said several physicians have also asked him if there is benefit to giving statins to patients who receive other types of chemotherapy. Neilan said there is a movement in oncology toward much more targeted chemo agents. Certain immunotherapies are associated with myocarditis and the advancement of atherosclerosis. He does not think statins will help with the myocarditis, but might help with the atherosclerosis, but studies need to be conducted to test this.
Neilan added that, despite the trial being conducted during the COVID-19 pandemic study, it ended up with 100% enrollment, 100% baseline measurements for LVEF, 95% followup and above 90% drug compliance
Why test statins in lymphoma patients?
Scherrer-Crosbie said lymphoma was chosen because it is a relatively frequent cancer with about 90,000 patients. It has a high survival rate and anthracycline chemo is the primary treatment. She said about 20% of these patients develop heart failure from the chemotherapy. These known statistics offered a good baseline to test statin therapy and offered enough patients to power the study.
"We wanted to test statins because there was some experimental evidence from animal studies and in retrospective studies and a small prospective study that implied there would be some cardio-protective properties of atorvastatin," Scherrer-Crosbie explained.
There is still a big unanswered question related to the mechanism of action of atorvastatin that offers cardio-protective effects.
"Statins have pleiotropic effects, in particular effects against inflammation and effects against oxidative stress, so all these mechanisms are possibilities and these are things that we are looking at, but we don't have any results yet," Scherrer-Crosbie said.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com