Article

Safety of Reloading Prasugrel in Addition to Clopidogrel Loading in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC.
The American journal of cardiology (Impact Factor: 3.43). 12/2012; 111(6). DOI: 10.1016/j.amjcard.2012.11.058
Source: PubMed

ABSTRACT Patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) commonly receive a loading dose of either clopidogrel or prasugrel, in addition to aspirin. The present study aimed to assess the safety of reloading prasugrel in patients who had initially received a loading dose of clopidogrel compared to prasugrel loading alone. The study included a cohort of 606 consecutive patients with acute coronary syndrome who had received a 60-mg loading dose of prasugrel before PCI. These patients were then categorized into clopidogrel preloading (300 or 600 mg) followed by prasugrel reloading (CP-load group, n = 90) and prasugrel loading only (P-load group, n = 516). Both groups received a 10-mg maintenance dose of prasugrel after PCI. The primary end point was in-hospital Thrombolysis In Myocardial Infarction-defined major bleeding. The secondary end points were other in-hospital bleeding complications and major cardiovascular events. Patients in the CP-load group compared to the P-load group were younger, with lower rates of cardiovascular risk factors. Significantly more patients in the CP-load group presented with biomarker-positive myocardial infarction (80.0% vs 30.6%, p ≤0.001) and cardiogenic shock (5.6% vs 1.4%, p = 0.022). No significant differences (p = NS) were seen in Thrombolysis In Myocardial Infarction major bleeding (2.6% vs 2.8%), Thrombolysis In Myocardial Infarction major or minor bleeding (12.2% vs 7.0%), the need for blood transfusion (2.6% vs 2.1%), and vascular complications (1.3% vs 2.0%) between groups. The CP-load group experienced more in-hospital major adverse cardiac events (5.6% vs 1.6%, p = 0.031), urgent coronary artery bypass grafting (3.3% vs 0.2%, p = 0.011), and longer hospital and intensive care unit stays. In conclusion, preloading with clopidogrel should not be prohibitive to reloading with prasugrel in patients presenting with acute coronary syndrome and undergoing PCI with respect to bleeding and vascular complications.

2 Followers
 · 
71 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives The present study aimed to assess the pharmacodynamic response of a prasugrel 60-mg loading dose (LD) alone compared with prasugrel 60 mg added to clopidogrel 600 mg.Background Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) commonly receive a clopidogrel LD prior to angiography. Switching these patients to prasugrel may be desirable because higher platelet inhibition is expected.Methods In this open-label, multicenter, nonrandomized trial, 75 patients were categorized into 2 treatment strategies: Those who received a clopidogrel 600-mg LD and received a reloading dose of prasugrel 60 mg (clopidogrel/prasugrel group) and those who did not receive a clopidogrel LD and received a prasugrel 60-mg LD (prasugrel group). Platelet reactivity was assessed using VerifyNow P2Y12 reaction units (PRU) and Platelet Reactivity Index vasodilator-stimulated phosphoprotein phosphorylation (PRI-VASP) at 3 different times: at the sheath insertion prior to prasugrel LD, 4 hours after prasugrel LD, and at discharge.ResultsFour hours after prasugrel LD, platelet reactivity did not differ between the clopidogrel/prasugrel group and the prasugrel group according to the VerifyNow assay (median PRU 23 [5–71] vs. 54 [5–91], respectively; P = 0.18) and the VASP assay (median PRI 8.67 [4.51–16.85] versus 8.03 [4.82–21.72], respectively; P = 1.0). No significant differences in PRU and PRI were observed at discharge. Few bleeding events were reported without any significant differences between the 2 groups.Conclusions Platelet reactivity with prasugrel 60 mg added to a clopidogrel 600-mg LD was not significantly different compared with prasugrel 60 mg alone in ACS patients undergoing PCI.
    Journal of Interventional Cardiology 07/2014; 27(4). DOI:10.1111/joic.12139 · 1.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prasugrel has been shown to be superior to clopidogrel in the setting of ACS patients undergoing coronary angioplasty. However, few data have been reported so far on those patients who switch from clopidogrel to prasugrel after coronary angioplasty. Aim of the current study was to evaluate the safety of prasugrel loading dose administration in ACS patients undergoing PCI and preatreated with high-dose clopidogrel. From May 2010 to December 2011 150 ACS patients undergoing coronary angioplasty and pretreated with high-dose clopidogrel, were switched to prasugrel loading dose soon after the procedure. They were matched (ratio 1:2) according to sex and age with a group of 300 ACS patients undergoing angioplasty and treated with high-dose clopidogrel only from May 2010 to December 2011. All demographic clinical and angiographic were collected. Primary endpoint was the rate of major bleeding complications (according to ACUITY trial definition) at 30-day follow-up. Secondary endpoints were: TIMI major and minor bleeding, definite stent thrombosis, major adverse cardiac events (MACE) and Net adverse cardiac events (NACE) at 30-day follow-up. The two groups of patients showed similar baseline demographic, and clinical characteristics. Most of the patients had unstable angina or non-ST segment elevation myocardial infarction. Almost (about 95 %) all patients underwent radial approach. No difference was observed in major bleeding complications according to both ACUITY (2.0 vs 2.0 %) and TIMI Major (0.7 vs 1.3 %) definition. No difference between the two groups was observed in terms of in-stent thrombosis, MACE and NACE at 30-day follow-up. Our observational study showed that switching to prasugrel with loading dose soon after angioplasty among ACS patients who were pretreated with clopidogrel seems to be well tolerated without overt evidence of heightened major bleeding. Future large randomized trials are certainly needed to confirm these findings.
    Journal of Thrombosis and Thrombolysis 03/2014; 38(3). DOI:10.1007/s11239-013-1039-0 · 2.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are very few clinical data concerning the safety of switching from clopidogrel to prasugrel in patients undergoing coronary stenting. However, in the daily activity, clinicians face the decision of switching patients at high-risk of thrombotic events from clopidogrel to prasugrel. Thus, we sought to evaluate clinical events in patients undergoing coronary stent implantation and prasugrel therapy with (SWITCH group) or without (NAÏVE group) prior clopidogrel therapy. A total of 454 patients with stable or unstable coronary artery disease, aged 70 ± 10 years, underwent non-emergent stent implantation and received prasugrel therapy. Of these, 315 (69 %) patients received clopidogrel before switching to prasugrel therapy. In 239 patients with high residual platelet reactivity (HRPR) on clopidogrel, prasugrel decreased platelet aggregation from 72 ± 11 to 43 ± 16 % (p < 0.001). There was no difference in in-hospital major or minor TIMI bleeding (2.8 vs. 4.3 %; p = 0.411) between the SWITCH and NAÏVE groups as well as in mortality, acute stent thrombosis, reinfarction and stroke rates. At multivariable analysis, independent predictors of bleeding were female gender (OR 5.56 [1.41-19.88] p = 0.014) and chronic renal failure (OR 6.27 [1.59-21.65] p = 0.009), but switching therapy did not. This result was confirmed after switching propensity score adjustment (c-statistic 0.81; Hosmer-Lemeshow test p = 860). Switching from clopidogrel to prasugrel in patients undergoing non-emergent coronary stent implantation seems to be tolerated with no overt signs of increased bleeding.
    Journal of Thrombosis and Thrombolysis 03/2014; 38(3). DOI:10.1007/s11239-013-1040-7 · 2.04 Impact Factor