PRAGUE-8: Pretreatment with clopidogrel before angiography not justified in stable CAD patients

September 03, 2007

Vienna, Austria - Routinely pretreating stable coronary artery disease patients before angiography with clopidogrel, primarily to achieve therapeutic levels in time for possible coronary intervention, increased the risk of bleeding complications and failed to reduce the risk of ischemic periprocedural complications, according to the results of a new study[1].

Dr Petr Widimsky

Presenting the results of the PRAGUE-8 study here at the European Society of Cardiology (ESC) Congress 2007, investigators, led by Dr Petr Widimsky (Charles University, Prague, Czech Republic), said that pretreatment with clopidogrel before coronary angiography is not justified and that clopidogrel can safely be given to these stable patients after angiography and before the PCI.

"There has been a mixture of data from acute coronary syndrome patients extrapolated to stable coronary patients," Widimsky told heart wire . "But these are very different populations. You can see this worldwide, with discussions of the treatment of stable coronary patients, with the COURAGE trial, but this doesn't apply to acute coronary syndrome patients, who are at much higher risk and who stand to benefit much more from PCI, as well as from clopidogrel. In this case, extrapolating the data from an ACS population to stable coronary patients is not justified. We observed an increased risk of bleeding and no treatment benefit."

Are the European guidelines valid?

Presenting the findings to the media, Widimsky said that clopidogrel pretreatment before planned PCI has been shown to reduce periprocedural complications, but that in current practice, very few PCIs are planned. Instead, after coronary angiography, the stable patient is whisked away for an unplanned, or "ad hoc," PCI. Because clopidogrel 600 mg takes up to two hours to achieve therapeutic levels, expert European consensus, which formed the basis for the ESC guidelines for PCI, recommended clopidogrel pretreatment for all elective coronary angiographies, even in those with stable coronary disease.

Widimsky told heart wire , however, that there is no prospective, randomized data supporting this recommendation, and for that reason, the PRAGUE-8 investigators compared the benefits and risks of pretreating patients with clopidogrel before elective coronary angiography vs adding clopidogrel in the cath lab only to patients undergoing subsequent PCI. In total, 513 stable CAD patients representing the "nonselective" strategy were treated with clopidogrel more than six hours before the elective coronary angiography and 515 "selective" patients were treated with clopidogrel in the lab after angiography if the patient was to undergo PCI.

In terms of the primary end point, defined as death, periprocedural MI, stroke or transient ischemic attack, or reintervention within seven days, there was no significant difference between those treated with the nonselective or selective clopidogrel treatment strategy. In addition, myocardial damage, as measured by periprocedural troponin levels, was not different between the two treatment strategies. Both findings were observed in all study patients and those who underwent PCI. There was, however, significantly more bleeding among patients who were treated with clopidogrel before coronary angiography.

PRAGUE-8: Clinically significant (major and minor bleeding) bleeding complications

Patients Nonselective clopidogrel treatment strategy (n=513) (%) Selective clopidogrel treatment strategy (n=515) (%) p
All study patients 3.5 1.2 0.02
Only patients who underwent PCI 7.2 0.7 0.006

Dr Christian Hamm (University Hospital Eppendorf, Hamburg, Germany), who moderated the press conference where the late-breaking clinical trial was presented to the media, agreed with the PRAGUE-8 investigators. "These are different patients from acute coronary syndrome patients, where there is a very high likelihood they will undergo an intervention," said Hamm. "Those guidelines won't change, but this study will have an effect on the PCI guidelines, because pretreatment with clopidogrel before angiography should not be routine."

Discussing the trial during the late-breaking-trials session, Dr Franz-Josef Neumann (University of Freiburg, Bad Krozingen, Germany) said that previous trials, including PCI-CURE, CREDO, EPISTENT, and ESPIRIT, showed that pretreating patients with clopidogrel reduced the early risks associated with PCI. However, the issue is whether or not this supposed benefit is significant enough to warrant widespread clopidogrel pretreatment in patients undergoing diagnostic angiography, he said.

The risk of bleeding in PRAGUE-8, however, differed significantly from CURE and CREDO, two trials where there was no significant risk of bleeding in patients pretreated with clopidogrel. The group of patients undergoing PCI, and not the patients who underwent diagnostic catheterization, primarily drove the risk of bleeding in PRAGUE-8, said Neumann. He added that the study was not powered to rule out benefit seen in previous studies and did not demonstrate any significant harm in those undergoing diagnostic catheterization.

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