Prasugrel Noninferior to Ticagrelor in STEMI, but Both Require Hours to Achieve Effect

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Prasugrel is noninferior to ticagrelor in the treatment of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), according to a small study published in the April 16, 2013, issue of the Journal of the American College of Cardiology. However, at least 4 hours are required to achieve effective platelet inhibition in the majority of patients, regardless of which antiplatelet agent is used.

For the RAPID (Rapid Activity of Platelet Inhibitor Drugs) trial, Guido Parodi, MD, PhD, of Careggi Hospital (Florence, Italy), and colleagues randomized 50 STEMI patients undergoing primary PCI with bivalirudin monotherapy to a loading dose of either prasugrel 60 mg (n = 25) or ticagrelor 180 mg (n = 25). Residual platelet activity was assessed using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) at baseline and 2, 4, 8, and 12 hours.

Three to 5 Hours Later, Effective Platelet Inhibition

After 2 hours, overall PRU values ranged from 2 to 398 with a median value of 242. There was no difference between prasugrel and ticagrelor PRU values (217 vs. 275; P = 0.207), meeting noninferiority criteria. Prasugrel resulted in less platelet inhibition compared with ticagrelor at 8 hours (P < 0.01). Still, the mean time to transition patients from the high platelet reactivity range (PRU ≤ 240) was 3 ± 2 hours for prasugrel and 5 ± 4 hours for ticagrelor.

Morphine use (OR 5.29; 95% CI 1.44-19.49; P = 0.012) and baseline PRU value (OR 1.014; 95% CI 1.00-1.03; P = 0.046) were the only independent predictors of high platelet reactivity.

Event rates did not differ between the treatment arms, but those treated with ticagrelor reported a higher rate of dyspnea and contrast-induced nephropathy. Additionally, 2 patients treated with ticagrelor died due to refractory heart failure, and 1 patient with high platelet reactivity in the prasugrel group experienced stent thrombosis 3 hours after primary PCI (table 1).

Table 1. In-Hospital Outcomes

 

Prasugrel
(n = 25)

Ticagrelor
(n = 25)

P Value

Death

0

8%

0.149

MI

4%

0

0.312

Stent Thrombosis

4%

0

0.312

Dyspnea

0

20%

0.018

Contrast-Induced Nephropathy

0

20%

0.018


Questions Regarding Absorption

The authors note that the wide variability of drug response seen in the study suggests that “the gastrointestinal absorption of orally administered drugs may be limited or delayed in STEMI patients because of multiple reasons including reduced or delayed drug absorption in patients with hemodynamic disarrangement, systemic vasoconstriction, adrenergic activation, and at high risk of vomit.”

In addition, since more than half of patients showed high platelet reactivity after 2 hours, “this means that the majority of the procedures of stenting of the infarct-related artery were performed without functional evidence of a significant antiplatelet effect,” Dr. Parodi and colleagues write, adding that different pharmacologic strategies may need to be explored for the first hour after STEMI onset.

Commenting on the association of morphine use with high platelet reactivity, they note that they “do not know if it is only a play of chance or if it has biological basis likely related to the inhibition of the normal muscular activity of the stomach and the intestines, which may lead to vomit or delayed drug absorption. However, if these findings [are] confirmed by further studies, more caution should be used regarding morphine administration in STEMI patients,” they write.

 


Source:
Parodi G, Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol. 2013;61:1601-1606.

 

 

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Disclosures
  • RAPID was supported by the A.R. CARD Foundation.
  • Dr. Parodi reports receiving consulting or lecture fees from AstraZeneca, Daiichi Sankyo/Eli Lilly, and The Medicines Company.

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