麻豆传媒

In low-risk acute coronary syndrome (ACS) patients, early treatment with ticagrelor (Brilinta) provides more rigorous platelet inhibition after ad hoc percutaneous coronary intervention (PCI) than clopidogrel (Plavix) use, a pharmacodynamics study showed.

Patients treated with ticagrelor immediately after coronary angiography had 2 hours after loading (98.4 P2Y₁₂ reaction units [PRU] versus 257.5 PRU, P<0.001), , of Mount Sinai Medical Center in New York, and colleagues found.

The difference persisted even 8 hours after PCI (P<0.001), they reported in the Feb. 16 issue of the Journal of the American College of Cardiology, similar to the initial report from the Society for Cardiovascular Angiography and Interventions (SCAI) meeting last year.

"Overall, these results confirm the superior pharmacodynamic potency of ticagrelor over clopidogrel and expand upon prior investigations conducted in different clinical settings," Mehran's group concluded.

These results are in line with the "hypothesis that ticagrelor can blunt troponin release after PCI and prevent serious complications, such as stent thrombosis or myocardial infarction [MI]," Gilles Montalescot, MD, PhD, of Pitié-Salpêtrière University Hospital in Paris, and colleagues wrote in an accompanying editorial.

"Indeed, risk of bleeding complications and potential for prolonged hospitalization, particularly in patients requiring surgical revascularization, are reasons for many clinicians to wait to define coronary anatomy before starting a P2Y₁₂ receptor inhibitor," the authors wrote.

The shorter time now achieved in bringing patients to the cath lab, in combination with the development of other antiplatelet therapies, has "further questioned the need for early initiation of P2Y₁₂-inhibiting therapy," they added.

Nonetheless, the latest investigation of an alternative to clopidogrel comes in a time when "off-label use of prasugrel [Effien] and ticagrelor is increasingly frequent in elective PCI, especially when patients undergo high-risk elective procedures" -- such as left main stenting, bifurcations, and multiple stenting -- the editorialists suggested.

The prospective study included 100 biomarker-negative patients undergoing PCI between 2012 and 2014. Individuals were randomized to receive a loading dose of 180-mg ticagrelor or 600-mg clopidogrel before the intervention.

With the exception of prior coronary artery bypass graft being more common in the clopidogrel arm, baseline characteristics were comparable between groups.

The difference in the relative drop in platelet reactivity widened after the end of the procedure. At 2 hours, the ticagrelor recipients had a greater reduction in PRU levels from baseline than their clopidogrel counterparts (66.6% versus 13.0%, P<0.001), a pattern also discernible at 8 hours (85.2% versus 32.7%, P<0.001).

Additionally, the incidence of high on-treatment platelet reactivity was reduced in the ticagrelor group compared with those receiving clopidogrel by the end of PCI (81.8% versus 97.7%, P=0.030), at 2 hours (13.3% versus 78.3%, P<0.001), and at 8 hours (2.4% versus 53.3%, P<0.001).

The discrepancy was not yet significant at the half-hour mark (84.1% versus 86.7%, P=0.77), however.

"Although we observed significant differences between clopidogrel and ticagrelor by the end of PCI in our study, rates of high on-treatment platelet reactivity were still high overall. This is also likely to be true in higher-risk ACS settings, such as in ST-segment elevation MI patients," the authors wrote.

In those cases, "crushing ticagrelor achieves faster platelet inhibition compared with whole tablets. Cangrelor [Kengreal] may also represent an additional treatment alternative to achieve immediate platelet inhibition."

The authors pointed out that their study was not powered for assessing clinical events, although prior studies have linked reduced high residual platelet reactivity to fewer thrombotic complications.

And although the findings might not necessarily apply to patients of elective or urgent PCI, Montalescot and colleagues suggested some potential.

"Elective PCI performed in stable coronary artery disease patients looks like a new potential indication for ticagrelor. There is a medical demand from physicians for intuitive protection when complex revascularization procedures are performed, a strategy somewhat supported by guidelines," they noted.

But "whether a medical need exists for patients will be known only after the results of the ongoing trials are published," they conceded, adding that the upcoming TWILIGHT and ALPHEUS investigations will focus on outcomes for ticagrelor recipients considered to be at high risk.