Is P2Y12 inhibitor therapy associated with an increased risk of cancer?

Antiplatelet therapy is a mainstay of cardiovascular therapy and is well established in clinical routine. Recently, the potential risk of solid cancers with P2Y12 inhibitor therapy has been an issue of growing interest. The alleged association primarily originated from the findings of an US Food and Drug Administration (FDA) review of the randomized controlled TRITON-TIMI 38 trial and the following results of the DAPT trial. The higher risk of cancer was predominately observed with the newer, more potent P2Y12 inhibitors and in the setting of prolonged dual antiplatelet therapy (DAPT). Current European Society of Cardiology (ESC) Guidelines suggest consideration of prolonged DAPT beyond the recommended duration of 6 months in stable coronary artery disease and 12 months in acute coronary syndrome if ischaemic risk prevails over the risk of bleeding. Several trials, studies and meta-analyses have addressed the potential interplay of cancer and P2Y12 inhibition since then. The effect of P2Y12 inhibition on cancer has been investigated extensively in basic research as well. In this review, we summarize current available evidence of cancer risk with P2Y12 inhibitor therapy and discuss the resulting clinical implications.