Taking a higher dose of carfilzomib, an anti-cancer drug, may increase the risk of cardiovascular problems, a study warns. An analysis of past studies showed 18 per cent of multiple myeloma patients receiving carfilzomib experienced cardiovascular adverse events (CVAE) such as hypertension, heart failure, heart attacks, or arrhythmia. More than eight per cent of patients experienced high- grade CVAEs that are more severe, which is more than twice as common as with other drugs for treating relapsed myeloma. Carfilzomib is one of three proteasome inhibitors currently approved for use by the US Food and Drug Administration (FDA), said researchers from the University of Pennsylvania in the US. Proteasomes are essentially garbage workers that break down and eliminate proteins inside a cell. Diseases that require more protein turnover to survive, like Multiple myeloma (MM), need more proteasomes. The inhibitor drugs block them from doing their job, causing the cells to fill up with protein and die.
“Like any cancer therapy, the concern with this approach is that it may have an effect on an otherwise healthy part of the body – in this case, the heart,” said Adam J Waxman, from the University of Pennsylvania. For the study published in the journal JAMA Oncology, the researchers gathered data from 24 studies reported from 2007 through 2017, which included information on 2,594 MM patients. They found 18.1 per cent of patients who took carfilzomib experienced CVAE, with 8.2 per cent of those cases being grade three or higher, meaning they are categorised as severe.
For comparison, a similar review of bortezomib, another proteasome inhibitor, found just 3.8 per cent of patients experienced CVAE and only 2.3 per cent were severe. The most common CVAEs were hypertension (12.2 per cent) and heart failure (4.1 per cent). Arrhythmias (2.4 per cent) and ischemic events (1.8) – in which there isn’t enough blood flow to the heart leading to the death of heart muscle – were observed less commonly. They also found that higher doses of carfilzomib are associated with higher rates of CVAE, and that carfilzomib was associated with an elevated risk of CVAE compared to control groups who did not receive carfilzomib.