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Giving IV fentanyl (Sublimaze) for pain control during coronary angiography may hamper the antiplatelet effect of ticagrelor (Brilinta) during percutaneous coronary intervention (PCI), a trial showed.

Of 212 adults randomized to elective coronary angiography with or without IV fentanyl, 70 required PCI and were loaded with 180-mg ticagrelor after diagnostic angiography in the Platelet Aggregation with Ticagrelor Inhibition and Fentanyl (PACIFY) trial.

Overall, for those who got fentanyl during the 24 hours after loading (area under the concentration-time curve P=0.05), though the gap had closed between groups by hour 4, John McEvoy, MB BCh, of Johns Hopkins, and colleagues reported online in Circulation.

An assessment of platelet function showed higher platelet reactivity 2 hours after ticagrelor loading if patients got fentanyl, a difference approaching significance on the VerifyNow P2Y12 Reaction Unit (PRU) assay (20% for fentanyl and 6% for no-fentanyl groups, P=0.07) and confirmed on aggregometry (33% versus 5%, P=0.03). As with ticagrelor plasma concentration, PRU was no longer different between groups at the 4-hour mark.

McEvoy and colleagues also reported average high-sensitivity troponin-I levels at 2 hours were 6.7 ng/L without fentanyl and 12.1 ng/L with fentanyl (P=0.02). The fentanyl arm had one case of acute stent thrombosis and another one of catheter thrombosis. There were no thrombotic events in no-fentanyl arm.

"This trial demonstrates that fentanyl administration lowers plasma concentrations of ticagrelor and delays its antiplatelet effects. Our results extend previous studies reporting that morphine delays the absorption of clopidogrel [Plavix], ticagrelor, and prasugrel [Effient] and impairs P2Y12 inhibition," the authors concluded. It has been theorized that this occurs through a slowdown in gastric emptying.

"The PACIFY trial results suggest that routine use of fentanyl should be discouraged during PCI in the absence of pain, particularly when P2Y12 agents are loaded near the time of administration of opiates. The practice of prophylactic fentanyl at the start of catheterization and PCI procedures may require reconsideration; though we cannot advocate for withholding this opiate where necessary for the treatment of pain," they suggested.

Notably, patients reported that the maximum pain they experienced during PCI reached 1.5 on a 10-point scale with fentanyl versus 2.3 without (P=0.14).

Fentanyl dosing was not specified in this single-center trial, but patients in both groups got subcutaneous lidocaine and IV midazolam at the start of the catheterization procedure and as needed thereafter. Pre-procedural opiate use was an exclusion criterion.

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