Author + information
- Fairoz Belary Abdul,
- Richard Anderson,
- Laurence Thornhill,
- Keith Morris and
- Phillip E. James
Background: We have previously shown that thienopyridines can form nitrosothiol derivatives (Th-SNO) in vitro and in vivo. These Th-SNO compounds exhibit typical nitrosothiol biochemistry with NO delivery and accentuate platelet inhibition.
Ticagrelor has a number of putative pleiotropic effects on the vasculature and can form R-SNO in vitro. We therefore investigated the effect of ticagrelor loading (2hrs) and chronic treatment on NO metabolite formation, with emphasis on SNO bio-synthesis in patients undergoing PCI for stable angina.
Methods. Blood samples were collected from 24 patients with coronary artery disease pre and 2 hrs post loading with Ticagrelor 180mg. Additionally, the chronic effects on NO metabolites was studied in 23 patients receiving Ticagrelor 90mg bd for > 28 days. We further subdivided patients on the basis of concomitant PPI ingestion.
Ozone-based chemiluminescence techniques were used to measure nitrite, nitrate, and nitrosothiol (RSNO) in blood samples. Platelet aggregation was measured using Multiplate® aggregometry using the ADP and TRAP agonist.
Results: Pre and post Ticagrelor doses showed a significant reduction in ADP (P=0.0001) and TRAP (p=0.0002) from 661.4 AU*min to 164 and 514 AU*min to 321 respectively. There was no change in plasma nitrite and nitrite post Ticagrelor loading however there was a marked increase in plasma nitrosothiols (R-SNO) from 19.65+/-3.3 nmol/L to 35.45+/-5.8 nmol/L (p=0.0072). Concurrent PPI therapy had no significant interactive effect on the formation of R-SNO post loading. Patients on chronic Ticagrelor had normalized R-SNO levels and had no persistent effect on NO metabolites.
Conclusions: This is the first demonstration of significant S-nitrosothiol (R-SNO) formation with an antiplatelet drug specifically a loading dose of Ticagrelor in patients undergoing PCI. This was not affected by PPI's. R-SNO levels normalized on chronic therapy with a slight increase in platelet aggregation. Given the potent antiplatelet effects of RSNO, this is an exciting and novel discovery and may play some part in the rapid onset platelet inhibition seen and some of the potential pleiotropic effects seen in preclinical studies with Ticagrelor.
Poster Hall, Hall C
Friday, March 17, 2017, 10:00 a.m.-10:45 a.m.
Session Title: Novel Mechanisms Underlying Ischemia-Reperfusion Injury in AMI
Abstract Category: 1. Acute and Stable Ischemic Heart Disease: Basic
Presentation Number: 1124-301
- 2017 American College of Cardiology Foundation