The PRAC has concluded the review of a safety signal of sudden or cardiac death with Imbruvica (ibrutinib) when used in combination with angiotensin-converting enzyme (ACE) inhibitors. 
Imbruvica is a medicine for treating the blood cancers mantle cell lymphoma, chronic lymphocytic leukaemia (CLL) and Waldenström’s macroglobulinaemia (also known as lymphoplasmacytic lymphoma).

Interim data from a clinical trial suggested that the risk of sudden or cardiac death in patients on an ACE inhibitor when entering the study may be increased in patients randomised to ibrutinib and rituximab, compared to those randomised to fludarabine, cyclophosphamide and rituximab.
After reviewing additional analyses from different sources including other clinical trials, the PRAC has concluded that the possible association between treatment with Imbruvica with concomitant use of ACE inhibitors and the risk of sudden or cardiac death does not seem to be plausible. 

Among the patients enrolled in the clinical trials sponsored by the marketing authorisation holder, there were no statistically significant differences in events of sudden or cardiac death between those treated with ACE inhibitors and Imbruvica, and those who received ACE inhibitors and a comparator.
The committee has therefore decided that although some cardiac adverse reactions are already known for Imbruvica, a further analysis of serious cardiac events is considered necessary in order to determine if these events might be linked to the use of Imbruvica alone and better characterise the risk of cardiotoxicity with the medicine, regardless of ACE inhibitor use. 

The further review will be performed through a separate regulatory procedure; therefore, this signal procedure is closed.