NEW ORLEANS – Atorvastatin treatment of patients with lymphoma receiving treatment with an anthracycline significantly reduced the incidence of incident cardiac dysfunction by approximately two-thirds during 12 months of treatment, in a multicenter randomized trial with 300 enrolled patients.
“These data support the use of atorvastatin among lymphoma patients receiving anthracycline therapy, where prevention of cardiac systolic dysfunction is important,” he concluded. Thomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. He noted that one important difference between the new study, AC STOPand a major previous study with a neutral effect published in 2022, which STOP-CA “was driven by a major change” in cardiac function as the study’s primary outcome, a decrease from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.
“We can consider these drugs [atorvastatin] for patients at increased risk of anthracycline cardiac toxicity, such as patients receiving a higher dose of an anthracycline, older patients, people with obesity, and women, he commented. Dr. Anita Deswal, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved in the study.
A foundation for an “important conversation” with patients
“For patients receiving higher doses of anthracyclines, the STOP-CA trial says whether starting a statin for cardiac protection is now an important discussion” for these patients to have with their treating physicians. “That was not the case before today,” he said. Dr. Ronald M. Wittelescardiologist and professor specializing in cardio-oncology at Stanford University (California).
“For a patient treated for lymphoma or other cancer and treated with the same or higher doses of anthracycline, such as sarcoma patients, the results of this trial warrant, at a minimum, a discussion between physicians and patients in making the decision,” he said. Dr. Witteles, who was not involved in the study, in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for imaging rather than a clinical endpoint.”
The experts noted that a similar study using the clinical endpoint of heart failure would require many more randomized patients and much longer follow-up. STOP-CA did not receive power for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no difference between groups.
STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled for anthracycline treatment at eight centers in the US and one in Canada, excluding patients already on statin therapy or those for whom that a statin had already been indicated. Of the 300 enrolled patients, 286 had a 12-month follow-up. Randomization assigned patients to receive atorvastatin 40 mg daily or placebo.
His mean cumulative dose of anthracyclines was 300 mg/m2, which is typical for treating lymphoma, but higher than the typical dose used for breast cancer patients. At baseline, the average LVEF was 63% and after 12 months it had decreased to 59%. Forty-six of the 286 patients evaluated after 12 months met the primary outcome of at least a 10 percentage point reduction from baseline in their LVEF and a decrease in LVEF to less than 55%. Investigators used cardiac MRI to assess LVEF at baseline and in most patients during follow-up, but a minority of patients underwent follow-up echocardiographic assessments due to logistical issues. More than 90% of patients adhered to the assigned regimen.
Tripled incidence of cardiac dysfunction in placebo patients
The incidence of this outcome was 9% among patients receiving atorvastatin and 22% among those receiving placebo, a significant difference. The calculated probability of the primary outcome was 2.9 times more likely among placebo-treated patients compared with atorvastatin-treated patients, also a significant difference.
The secondary outcome of the study was patients who had at least a 5% drop from baseline in their LVEF and with an LVEF of less than 55% after 12 months. This outcome occurred in 13% of atorvastatin-treated patients and 29% of placebo-treated patients, a significant difference.
The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with approximately similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the included patients developed myositis.
Treatment with atorvastatin also produced an expected average decrease of 37% from baseline in LDL cholesterol levels.
“This was an important and well-designed trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, including lymphoma and sarcoma, and the cardiac side effects of developing cardiac dysfunction are unequivocally real.”
The importance of a clinically significant effect
The results are in particular contrast to the findings of the PREVENT study, published in 2022, which compared atorvastatin 40 mg daily with placebo in 279 randomized breast cancer patients treated for 24 months. However, patients on PREVENT had a median cumulative anthracycline dose of 240 mg/m2and the main outcome of the study was the mean change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a non-significant difference.
In STOP-CA, the average change in LVEF from baseline was a 1 percentage point reduction in the placebo group compared with atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant.” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from the reviewers early on to design their study to track a clinically significant change in LVEF rather than just looking at the average overall change.
dr. Deswal also noted that future studies are unlikely to examine the efficacy of a statin in preventing LVEF in patients with the full range of cancers who are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the STOP-CA results to patients with other types of cancer.
STOP-CA did not receive commercial funding. dr. Neilan has consulted and received honoraria from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grants from AstraZeneca and Bristol-Myers Squib. dr. Desval and Dr. Witteles had no relevant disclosures.
This article originally appeared on mdedge.compart of the Medscape professional network.