News Release: Sacubitril/Valsartan May Reduce Chemotherapy-Induced Cardiotoxicity in High-Risk Cancer Patients

Introduction: A recent study presented at the American Heart Association’s Scientific Sessions 2024 introduces sacubitril/valsartan, a widely used heart failure medication, as a potential protective agent against heart damage in high-risk cancer patients undergoing anthracycline chemotherapy. Anthracyclines, while effective for treating various cancers such as breast cancer, leukemia, and lymphoma, carry a significant risk of cardiotoxicity, leading to cardiomyopathy and heart failure. The SARAH trial aimed to evaluate whether sacubitril/valsartan could mitigate this risk and preserve cardiac function during chemotherapy.

Highlights: The SARAH trial was a randomized, double-blind, placebo-controlled study involving 114 high-risk cancer patients at Erasto Gaertner Hospital in Curitiba, Brazil. High risk was defined by elevated high-sensitivity troponin I levels post-anthracycline infusion, indicating early signs of cardiac injury. Participants, predominantly women with breast cancer (81%), were randomized to receive sacubitril/valsartan or a placebo over 24 weeks.

Key findings include:

• Significant Reduction in Cardiotoxicity: Sacubitril/valsartan was associated with a 77% reduction in the relative risk of cardiotoxicity compared to placebo. Cardiotoxicity was measured as a ≥15% reduction in global longitudinal strain (GLS), a sensitive marker of left ventricular function.
• Improvement in Cardiac Function: Patients in the sacubitril/valsartan group experienced an average improvement in GLS by 2.55%, whereas those in the placebo group showed an average decline of 6.65%.
• Dose Titration and Tolerance: The medication was initiated at a dose of 24/26 mg twice daily and titrated every two weeks to a target of 97/103 mg twice daily or the highest tolerated dose without side effects. It was generally well tolerated, with hypotension being more common in the treatment group (14% vs. 1.8%) but no significant differences in other adverse events.
• Independent of Other Factors: The protective effect of sacubitril/valsartan was consistent regardless of cumulative anthracycline dose, HER2 status, presence of hypertension, or patient age.

Conclusion: The findings from the SARAH trial suggest that sacubitril/valsartan may offer a promising strategy to prevent chemotherapy-induced cardiotoxicity in high-risk cancer patients. By preserving cardiac function during anthracycline treatment, this medication has the potential to improve patient outcomes, enhance quality of life, and reduce the long-term burden of heart failure among cancer survivors. Further research with larger, more diverse populations and extended follow-up is warranted to confirm these results and assess the impact on long-term clinical outcomes.

Source: This research was conducted by the Heart Institute at the University of São Paulo, Brazil, and presented at the American Heart Association Scientific Sessions 2024.

Primary Source: American Heart Association News Release
https://newsroom.heart.org/news/a-common-heart-failure-medication-may-help-prevent-heart-damage-related-to-chemotherapy-6906417

Secondary Sources:

• American College of Cardiology Summary of the SARAH Trial
  https://www.acc.org/Latest-in-Cardiology/Articles/2024/11/13/21/17/mon-915am-sarah-aha-2024
• TCTMD Article: “ARNI Lessens Anthracycline Cardiotoxicity in High-Risk Patients: SARAH”
  https://www.tctmd.com/news/arni-lessens-anthracycline-cardiotoxicity-high-risk-patients-sarah