Population

Patients with STEMI on a maintenance dose of ticagrelor 90 mg twice daily or prasugrel 10 mg once daily following primary PCI were enrolled prospectively. Treatment was left at the physician’s discretion. One month after discharge, platelet reactivity was evaluated using VASP-PRI, VN-P2Y ₁₂ and LTA assays on the same blood sample. Patients with a low platelet count (< 150,000/mL) were excluded. Patient characteristics were entered into a prospective web-based registry, including drug intake to evaluate potential drug-drug interaction. The Pitié-Salpêtrière University Hospital Ethics Committee approved the protocol and the study was conducted in accordance with the Declaration of Helsinki.

Laboratory procedures

Blood was collected into Becton-Dickinson 3.2% citrate vacuette tubes by venous puncture after discarding the first mL of blood. Pharmacodynamic evaluation was performed simultaneously for the three PFTs.

Phosphorylation of the VASP was measured with a Beckman Coulter FC500 cytometer (Beckman Coulter, Villepinte, France) according to the manufacturer’s instructions and previous studies . Blood samples were incubated in vitro with adenosine diphosphate (ADP) and prostaglandin E ₁ (PGE ₁ ) before fixation. The VASP-PRI measured by a flow cytometer was calculated from the median fluorescence intensity (MFI) for each condition according to the formula: VASP-PRI = ([MFI (PGE ₁ ) – MFI (PGE ₁ + ADP)]/MFI [PGE ₁ ]) × 100.

For the VN-P2Y ₁₂ assay, samples were run according to the package insert. Results were expressed in P2Y ₁₂ reaction units (PRU), in response to iso-thrombin receptor activating peptide (iso-TRAP) and ADP-PGE ₁ , and as percentage of inhibition, corresponding to the ratio of the results of the ADP-PGE ₁ and iso-TRAP channels.

For LTA, platelet-rich plasma was obtained by centrifugation of citrated whole-blood at 100 g for 10 minutes at 20 °C. Platelet-poor plasma was obtained by further centrifugation at 2250 g for 15 minutes. In vitro platelet aggregation in platelet-rich plasma was measured at 37 °C by LTA (model 490-4D; Chrono-Log Corp., Kordia, The Netherlands) and was induced by the addition of ADP (Sigma-Aldrich, Saint Quentin Fallavier, France) at a final concentration of 20 μmol/L. All measurements were performed in duplicate and results were expressed in terms of maximal platelet aggregation (MPA) and residual platelet aggregation (RPA) measured at 6 minutes. Prespecified criteria used to define non-evaluable samples were: lack of sufficient signal, haemolysis, platelet count < 150,000/mL and an unstable baseline.

Study objective

The primary objective of the study was to compare the level of platelet inhibition 30 days after the acute event during maintenance therapy with ticagrelor 90 mg twice daily or prasugrel 10 mg once daily, using three validated PFTs. The secondary objectives were to compare the proportions of patients with high on-treatment platelet reactivity (HPR) and low on-treatment platelet reactivity (LPR), using the established cut-offs of VASP-PRI > 50%, PRU > 208 (VN-P2Y ₁₂ ) and RPA > 46.2% (LTA) for HPR and VASP-PRI < 16%, PRU < 85 (VN-P2Y ₁₂ ) and RPA < 10% (LTA) for LPR . Based on previous platelet function studies , 55 patients in each group were needed to yield 90% power with an alpha risk error of 0.05, assuming a 20% standard deviation, to demonstrate that one of the two drugs is superior to the other.

Statistical analysis

Continuous variables following a normal distribution are presented as means ± standard deviations and were compared using Student’s t -test. Categorical variables are presented as counts and percentages and were compared using Fisher’s exact test. Results are reported as means ± standard errors of the mean for the detailed analyses. All P values are two-sided and a value of P < 0.05 was considered significant. The relationship between the three assays was assessed by Pearson’s correlation coefficient. Normal distribution of the variables was evaluated for continuous variables using the Kolmogorov-Smirnov test. All analyses were performed with the use of PRISM, version 5 (GraphPad Software, Inc., LA Jolla, CA, USA). All the authors had full access to and take full responsibility for the integrity of the data.

Study population

A total of 118 patients with STEMI exposed to a 10 mg maintenance dose of prasugrel once daily ( n = 60) or a 90 mg maintenance dose of ticagrelor twice daily ( n = 58) agreed to participate in the study and were assessed for platelet function testing at the 1-month follow-up visit. Baseline characteristics are presented in Table 1 .

Table 1

Baseline characteristics.

Characteristic	All patients ( n = 118)	Ticagrelor group ( n = 58)	Prasugrel group ( n = 60)	P
Age (years)	58.86 ± 1.03	59.97 ± 1.54	57.78 ± 1.37	0.29
Men (%)	83.05 ± 3.47	84.48 ± 4.80	81.67 ± 5.04	0.69
Weight (kg)	76.69 ± 1.34	75.64 ± 1.95	77.74 ± 1.84	0.43
BMI	26.24 ± 0.38	25.98 ± 0.50	26.50 ± 0.57	0.49
Low weight < 60 kg (%)	12.71 ± 3.08	18.97 ± 5.19	6.67 ± 3.28	0.05 a
BMI > 30 (%)	16.10 ± 3.40	10.34 ± 4.03	21.67 ± 5.36	0.10
Diabetes (%)	16.95 ± 3.47	15.52 ± 4.80	18.33 ± 5.04	0.69
Dyslipidaemia (%)	38.98 ± 4.51	44.83 ± 6.59	33.33 ± 6.14	0.20
Smoker (%)	72.03 ± 4.15	74.14 ± 5.80	70.00 ± 5.97	0.62
High blood pressure (%)	36.44 ± 4.45	39.66 ± 6.48	33.33 ± 6.14	0.48
Family history of CAD (%)	27.12 ± 4.11	31.03 ± 6.13	23.33 ± 5.51	0.35
One-vessel disease (%)	62.71 ± 4.47	68.97 ± 6.13	56.67 ± 6.45	0.17
Two-vessel disease (%)	22.88 ± 3.88	17.24 ± 5.00	28.33 ± 5.87	0.15
Three-vessel disease (%)	15.25 ± 3.32	15.52 ± 4.78	15.00 ± 4.65	0.93
Creatinine clearance (mL/min)	97.65 ± 3.10	88.69 ± 3.96	106.6 ± 4.51	0.003 a
Ejection fraction (%)	51.29 ± 9.16	49.13 ± 1.41	53.34 ± 1.13	0.02 a
Aspirin (mg)	100 ± 0	100 ± 0	100 ± 0	1.00
Beta-blockers (%)	91.53 ± 2.57	91.38 ± 3.72	91.67 ± 3.60	0.95
ACE inhibitors (%)	92.37 ± 2.45	91.38 ± 3.72	93.33 ± 3.25	0.69
Calcium antagonists (%)	8.47 ± 2.57	5.17 ± 2.93	11.67 ± 4.18	0.21
Statins (%)	99.15 ± 0.84	98.28 ± 1.72	100 ± 0	0.99
Proton pump inhibitors (%)	83.90 ± 3.398	79.31 ± 5.36	88.33 ± 4.18	0.18

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