Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Immune therapies represent a quantum leap in the fight against cancer. Recently approved immune checkpoint inhibitors that target receptors involved in immune escape of cancer cells (including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein ligand-1 (PD-L1) are increasingly being used for therapeutic benefit in a number of cancers. The robust anti-cancer activity of these agents has been accompanied by the recognition of new adverse effects, often due to the over activation of immune system, that may limit their therapeutic benefit and adversely impact outcomes. Combination treatments in particular, such as approaches using two targeted immunotherapy agents, have higher risk of adverse effects. Our review focuses on the approved checkpoint inhibitor therapies and their potential for cardiovascular toxicity. While very few cases of autoimmune cardiotoxicity and myocarditis have been reported in clinical trials, severe, life-threatening episodes of heart failure and hemodynamic compromise associated with the use of immune checkpoint inhibitors have recently been reported in the literature. Early recognition, diagnosis, and management of autoimmune myocarditis represent an important clinical challenge with no current guidelines available for prevention, identification, and treatment of this serious condition. This area of cardio-oncology is evolving rapidly as more drugs in this class are being discovered and pending approval. There is a need for future studies focused on prospective identification of biomarkers and clinical standards for treatment and long-term follow-up of cardiovascular toxicity to successfully continue the treatment of cancer while preventing the adverse outcomes with novel immune therapies.

The immune checkpoint inhibitors have brought about a paradigm shift in the treatment of many cancers and are being used as the first line therapy in increasing number of aggressive malignancies, including metastatic melanoma. Their adverse effects, mostly mediated by an uncontrolled overactivation of the immune system, may compromise the therapeutic benefit. Combination immune checkpoint therapies in particular, have higher therapeutic efficacy, but have also been associated with a higher incidence of severe immune-related adverse effects including autoimmune lymphocytic myocarditis. Recent clinical reports of this rare and life threatening condition indicated rapid progression of severe hemodynamic and electrical instability, with or without acute decompensated heart failure, reduced ejection fraction and shock, pointing to the need for early recognition, diagnosis and prompt management. Current guidelines for management of other immune-related adverse effects recommend high-dose glucocorticoids, with consideration of immunomodulators, such as infliximab in patients with severe colitis. However, knowledge about the treatment approaches in immune-related myocarditis remains extremely scarce. Here we report a case of severe, steroid refractory, lymphocytic myocarditis that occurred after the first cycle of combination immunotherapy with the programmed cell death protein-1 inhibitor, nivolumab, and the cytotoxic T-lymphocyte-associated protein 4 blocker, ipilimumab, for metastatic melanoma. We discuss treatment approaches including the role for transvenous pacemaker, advanced heart failure support, and interdisciplinary decision making.