Angiotensin Receptor Blockers Worsen Renal Function and Dyspnea on Ticagrelor: A Potential Ticagrelor-Angiotensin Receptor Blocker Interaction?

Authors


Abstract

Ticagrelor is a new antiplatelet agent that was pitted against clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Because ticagrelor is the first oral, reversible, twice-daily agent, sufficient information on drug interactions is not available. Our objective was to ascertain the safety of ticagrelor with other common medications. The US Food and Drug Administration Complete Response Review indicates that renal adverse events (AEs) and renal function AEs were higher in ticagrelor-treated patients who were concomitantly treated with angiotensin receptor blockers (ARBs) >50% of study days compared to ticagrelor-treated patients who did not receive ARBs >50% of study days. Clopidogrel-treated patients showed a trend for an increase in adverse renal events with ARB use. However, this was not as pronounced as that observed with ticagrelor. Dyspnea was also significantly increased in patients on concomitant ticagrelor-ARB compared to ticagrelor without concomitant ARB and clopidogrel (21.4% vs 14.6% vs 9.9%, respectively) as well as angioedema (0.15% vs 0.09%). Furthermore, in patients with a baseline estimated glomerular filtration rate (eGFR) <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel. In patients on ticagrelor, ARBs significantly increased the frequency of renal related AEs, renal function AEs, and dyspnea. Moreover, in patients with a baseline eGFR <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel.

Dr. Serebruany is listed as an inventor for the US patent application: TREATING CARDIAC ARRHYTHMIAS, HEART FAILURE, PERIPHERAL ARTERY DISEASE AND STROKE WITH CYCLOPENTYL-TRIAZOLO-PYRIMIDINE OR DERIVATIVE THEREOF (USN 61/253,829) assigned to HeartDrug™ Research, and received funding for research studies with clopidogrel, and consultant fees from both clopidogrel and ticagrelor manufacturers.

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