Double Ticagrelor Loading Dose vs Standard in STEMI
Double Ticagrelor Loading Dose vs Standard in STEMI
The 2 groups were well matched in all baseline characteristics (Table I), but there was a higher previous PCI rate in the ticagrelor group. The study drug LD was performed in 13 (26%) patients in the emergency department and in 37 (74%) patients in the catheterization laboratory, without differences between the 2 groups. Seventeen patients received 5,000 UI of unfractionated heparin in the ambulance or in the emergency department, with subsequent switching to bivalirudin. All, except for 2 patients who referred to be "allergic" to the drug, received intravenous aspirin before prasugrel or ticagrelor LD. Mean time between intravenous aspirin administration and prasugrel or ticagrelor LD was 51 ± 32 minutes.
The 1-hour PRU assessment was performed after PPCI in all patients. One hour after LD, PRU values ranged from 3 to 400 (median value 243 [137–299]). There was no difference in PRU value at 1 hour between the prasugrel and ticagrelor groups: 236 (129–289) and 248 (115–304), respectively (P = .899): no significant PRU difference was observed between the 2 groups at any time point (Figure 2). We also calculated IPA values that are able to correct for potential differences in baseline PRU (Figure 3); no significant IPA difference was observed between the 2 groups at any time point. The percentage of HRPR patients at different time points in the prasugrel and ticagrelor groups is reported in Figure 4. The independent predictors of HRPR 1 hour after LD were morphine use (OR 4.49 [1.19–16.88], P = .026) and baseline PRU value (OR 1.015 [1.00–1.03], P = .039). Five patients in each group showed very low (PRU ≤ 85) residual platelet reactivity 1 hour after LD.
(Enlarge Image)
Figure 2.
Kinetics of platelet inhibition over time. Residual platelet reactivity values assessed by PRU (lower curves) and ARU (upper curves) by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD in patients treated by 60-mg prasugrel LD (Δ) or 360-mg ticagrelor LD (□). P value nonsignificant for all comparisons.
(Enlarge Image)
Figure 3.
Inhibition of platelet aggregation over time. Inhibition of platelet aggregation by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD in patients treated by 60-mg prasugrel LD (Δ) or 360-mg ticagrelor LD (□). P value nonsignificant for all comparisons.
(Enlarge Image)
Figure 4.
Patients with HRPR over time. The percentage of HRPR (PRU ≥240) patients at different time points in the prasugrel (green bars) and ticagrelor (orange bars) groups. P value nonsignificant for all comparisons.
Baseline ARU ranged from 384 to 664 (median value: 452 [422–566]). The effect of intravenous aspirin LD assessed as ARU changes over time is reported in Figure 2 (upper curves). At each time point, about 90% of enrolled patients had an ARU value < 550 (Figure 5).
(Enlarge Image)
Figure 5.
Response to intravenous aspirin. The percentage of patients with high ARU (≥550) at different time points in the prasugrel (green bars) and ticagrelor (orange bars) groups. P value nonsignificant for all comparisons.
The clinical events observed are reported in Table II. There was no difference in event rates between the 2 study drugs. In particular, bleeding events, bradyarrhythmias, contrast-induced nephropathy, transaminases elevation, and dyspnea were not significantly increased by a 360-mg ticagrelor LD. There were 2 deaths: one due to cardiac tamponade in the prasugrel group and one due to refractory heart failure in the ticagrelor group. No acute stent thrombosis occurred. No patient discontinued prasugrel or ticagrelor, whereas 3 patients withdrew aspirin during hospital stay because of bleeding events.
Results
Baseline and Procedural Characteristics
The 2 groups were well matched in all baseline characteristics (Table I), but there was a higher previous PCI rate in the ticagrelor group. The study drug LD was performed in 13 (26%) patients in the emergency department and in 37 (74%) patients in the catheterization laboratory, without differences between the 2 groups. Seventeen patients received 5,000 UI of unfractionated heparin in the ambulance or in the emergency department, with subsequent switching to bivalirudin. All, except for 2 patients who referred to be "allergic" to the drug, received intravenous aspirin before prasugrel or ticagrelor LD. Mean time between intravenous aspirin administration and prasugrel or ticagrelor LD was 51 ± 32 minutes.
Residual Platelet Reactivity
The 1-hour PRU assessment was performed after PPCI in all patients. One hour after LD, PRU values ranged from 3 to 400 (median value 243 [137–299]). There was no difference in PRU value at 1 hour between the prasugrel and ticagrelor groups: 236 (129–289) and 248 (115–304), respectively (P = .899): no significant PRU difference was observed between the 2 groups at any time point (Figure 2). We also calculated IPA values that are able to correct for potential differences in baseline PRU (Figure 3); no significant IPA difference was observed between the 2 groups at any time point. The percentage of HRPR patients at different time points in the prasugrel and ticagrelor groups is reported in Figure 4. The independent predictors of HRPR 1 hour after LD were morphine use (OR 4.49 [1.19–16.88], P = .026) and baseline PRU value (OR 1.015 [1.00–1.03], P = .039). Five patients in each group showed very low (PRU ≤ 85) residual platelet reactivity 1 hour after LD.
(Enlarge Image)
Figure 2.
Kinetics of platelet inhibition over time. Residual platelet reactivity values assessed by PRU (lower curves) and ARU (upper curves) by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD in patients treated by 60-mg prasugrel LD (Δ) or 360-mg ticagrelor LD (□). P value nonsignificant for all comparisons.
(Enlarge Image)
Figure 3.
Inhibition of platelet aggregation over time. Inhibition of platelet aggregation by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD in patients treated by 60-mg prasugrel LD (Δ) or 360-mg ticagrelor LD (□). P value nonsignificant for all comparisons.
(Enlarge Image)
Figure 4.
Patients with HRPR over time. The percentage of HRPR (PRU ≥240) patients at different time points in the prasugrel (green bars) and ticagrelor (orange bars) groups. P value nonsignificant for all comparisons.
Aspirin Effect Assessment
Baseline ARU ranged from 384 to 664 (median value: 452 [422–566]). The effect of intravenous aspirin LD assessed as ARU changes over time is reported in Figure 2 (upper curves). At each time point, about 90% of enrolled patients had an ARU value < 550 (Figure 5).
(Enlarge Image)
Figure 5.
Response to intravenous aspirin. The percentage of patients with high ARU (≥550) at different time points in the prasugrel (green bars) and ticagrelor (orange bars) groups. P value nonsignificant for all comparisons.
In-hospital Outcome
The clinical events observed are reported in Table II. There was no difference in event rates between the 2 study drugs. In particular, bleeding events, bradyarrhythmias, contrast-induced nephropathy, transaminases elevation, and dyspnea were not significantly increased by a 360-mg ticagrelor LD. There were 2 deaths: one due to cardiac tamponade in the prasugrel group and one due to refractory heart failure in the ticagrelor group. No acute stent thrombosis occurred. No patient discontinued prasugrel or ticagrelor, whereas 3 patients withdrew aspirin during hospital stay because of bleeding events.
