Prasugrel Reloading Feasible After Clopidogrel Pretreatment in ACS Patients

Pretreatment with clopidogrel should not prohibit reloading with prasugrel in patients presenting with acute coronary syndromes (ACS) and undergoing percutaneous coronary intervention (PCI), according to a study published online January 2, 2013, ahead of print in the American Journal of Cardiology. The strategy does not appear to increase bleeding or vascular complications.

Investigators led by Ron Waksman, MD, of Washington Hospital Center (Washington, DC), retrospectively examined in-hospital outcomes for a cohort of 606 consecutive ACS patients who had received a 60-mg loading dose of prasugrel as well as clopidogrel (300 mg or 600 mg) before PCI, then were either reloaded after the procedure with prasugrel (n = 90) or not (n = 516).

Comparable Bleeding, Vascular Risk

The primary endpoint of TIMI major bleeding was similar in patients who were and were not reloaded with prasugrel. Also, there were no differences in combined TIMI major and minor bleeding, need for blood transfusion, major hematoma, and vascular complications between the 2 groups. Intracranial bleeding and retroperitoneal bleeding rates were similar as well, and no cases of gastrointestinal bleeding developed (table 1).

Table 1. In-Hospital Bleeding and Vascular Complications^a

^a P = NS for all comparisons.

All-cause and cardiac mortality were unaffected by prasugrel reloading, but the overall MACE rate was higher in those who received the extra prasugrel dose, a difference mainly driven by a greater need for urgent CABG. No cases of Q-wave MI or stent thrombosis occurred, although 1 patient not reloaded with prasugrel experienced a stroke (table 2).

Table 2. Other In-Hospital Outcomes

^a P = 0.011
^b P = 0.031

Based on these findings, “it is safe for physicians to reload prasugrel in patients at greater ischemic risk who initially received a preloading dose with clopidogrel,” Dr. Waksman and colleagues write.

“This issue of reloading prasugrel is important because it reflects clinical practice. Patients who present with ACS often initially receive a loading dose with clopidogrel in the emergency department or in the inpatient service before arriving at the cardiac catheterization laboratory,” they continue. “If the coronary anatomy is deemed suitable for PCI, the patient might be given an additional prasugrel loading dose just before the procedure. Patients with ACS who are treated medically, however, should continue receiving clopidogrel.”

Study Provides ‘Useful Guidance’

In a telephone interview, Dominick J. Angiolillo, MD, PhD, of the University of Florida College of Medicine (Jacksonville, FL), told TCTMD that it “appears to be okay” to give an extra dose of prasugrel in this context.

“In clinical practice, many patients are being pretreated at first clinical presentation with clopidogrel and it creates some hesitance on behalf of many interventionalists to switch to prasugrel because this was simply not tested in the clinical trial that led to the approval of prasugrel,” he said.

Dr. Angiolillo compared the current results with those of the prospective, randomized TRIPLET trial. Presented in May 2012 at EuroPCR in Paris, France, the pharmacodynamic study concluded that it is acceptable to reload prasugrel if an ACS patient was already loaded with clopidogrel. Still, “we need to keep in mind that these are not studies that are powered to provide definitive conclusions on safety and efficacy, but do provide useful guidance,” he noted.

In terms of an ideal patient for this treatment, Dr. Angiolillo said it is “difficult to make definitive conclusions based on studies that are not powered for analysis on subgroups.” He reported, however, that in his clinical practice he always reloads STEMI patients undergoing PCI and pretreated with clopidogrel. This is “because we know there is a time delay in the effects of clopidogrel, particularly in the setting of STEMI, [where the] pharmacodynamic effects . . . are reduced,” he explained.

Going forward there is a need to “ideally have sufficiently powered studies to reach more definitive conclusions on safety and efficacy, but since these are unlikely to occur we need to rely on large registry data as well as dedicated pharmacodymanic studies such as the TRIPLET trial which provide guidance and insights into this topic,” he concluded.

Study Details

A 10-mg maintenance dose of prasugrel was administered after PCI in both groups. All patients also received 325-mg aspirin before the procedure and were recommended to continue aspirin and prasugrel as maintenance therapy after PCI.

Patients were well matched in terms of baseline characteristics, but those who were not reloaded with prasugrel tended to be older and more often had diabetes, hypercholesterolemia, a history of CAD, and previous PCI. Those reloaded with prasugrel more often had cardiogenic shock and presentation with biomarker-positive MI.

 

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Source:
Loh JP, Pendyala LK, Kitabata H, et al. Safety of reloading prasugrel in addition to clopidogrel loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2013;Epub ahead of print.

 

 

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