Potential impact of nicorandil on the pharmacodynamics of anti-angiogenic agents

Abstract Anti-angiogenic agents are widely used to treat solid tumors. We previously demonstrated that nicorandil, an angina pectoris medication, counteracted the effects of bevacizumab in a human mini-tumor model. To further elucidate the potential pharmacodynamic interactions and possible clinical implications, we conducted an integrative investigation combining an in vivo mouse model and a large-scale analysis of clinical adverse event reports. In tumor-bearing nude mice, aflibercept treatment markedly increased systemic blood pressure and substantially reduced tumor volume, whereas co-administration of nicorandil mitigated both responses. Additionally, an analysis of the Unites States Food and Drug Administration Adverse Event Reporting System data (FAERS [JAPIC AERS]) was conducted. Concomitant use of anti-angiogenic agents and nicorandil was infrequently reported; therefore, this data must be interpreted with caution. However, the tendency of reduced reporting odds ratios of hypertension and proteinuria and instances of hypotension were documented. Collectively, these findings suggest that nicorandil may counteract the pharmacodynamic effects of anti-angiogenic agents when administered concurrently. Therefore, further clinical validation is warranted.