Multiple studies find benefits to clopidogrel pretreatment

The conclusions of three separate studies led researchers at the 2008 ACC Scientific Sessions to recommend clopidogrel pretreatment for at-risk heart patients.

First, an increase of plasminogen activator inhibitor 1 (PAI-1) after PCI with stent implantation may favor the development of stent thrombosis and in-stent restenosis due to inhibition of the fibrinolytic system; however, clopidogrel pretreatment before PCI may reduce major adverse cardiovascular events at one month, according to Katharina M. Katsaros, MD, and colleagues from Medical University of Vienna in Austria.

Katsaros and colleagues included 51 patients with stable angina who underwent elective PCI with stent implantation. At the time when the study was performed, the researchers said that routine use of clopidogrel before PCI was not advised and treatment was at the discretion of the referring cardiologist.

The Austrian investigators found that PCI induced a significant increase of PAI-1 levels in patients without pretreatment (+7.4ng/mL). In contrast, they reported that the procedure had no effect on PAI-1 active antigen in patients that were pretreated with clopidogrel (-3.2ng/mL) resulting in significantly lower plasma levels of PAI-1 compared to patients without pretreatment 24 hours after PCI (15.2 vs. 29.6 ng/mL).

Clopidogrel pretreatment completely abolishes the increase of PAI-1 active antigens after coronary stent implantation, which Katsaros and colleagues said “may explain in part the beneficial effects of this treatment regimen.”

In a second study presented at ACC08, Herbert D. Aronow from Michigan Heart & Vascular Institute in Ann Arbor and colleagues said they undertook the study because even though clopidogrel pretreatment reduces ischemic outcomes following PCI, many patients do not receive clopidogrel until after their PCI.

Aronow and colleagues examined the rate and predictors of clopidogrel pretreatment among 1,991 consecutive patients enrolled in Waves 4 (2004) and 5 (2006) of the NHLBI Dynamic PCI registry. The investigators said they defined clopidogrel pretreatment as a 300 or 600 mg loading dose given within 24 hours before the procedure.

The researchers reported that PCI was performed in the setting of an acute MI in 32 percent and unstable angina in 32 percent, and clopidogrel pretreatment was administered in 389 (19.5 percent) patients.

In a multivariable logistic regression model adjusting for clinical center, clopidogrel pretreatment was more common in Asians (vs. Whites), those with a history of prior PCI, those presenting with MI, those who received unfractionated or low molecular weight heparin or bivalrudin before the procedure and later in the study year, according to Aronow and colleagues. In contrast, clopidogrel initiation was less common before PCI among African Americans (vs. Whites), those in cardiogenic shock, ad hoc procedures and among patients who received beta blockers beforehand.

In the recent national multicenter PCI registry, Aronow and colleagues found that the decision to pretreat with clopidogrel was influenced by ethnicity, clinical presentation, concomitant medical therapies and year of enrollment. They also concluded that the NHLBI Dynamic PCI registry researchers found that strategies to improve utilization of clopidogrel treatment before PCI are needed.

A third study was undertaken to examine the effect of pretreatment with statins on the TIMI frame count in the culprit artery after successful PCI, according to Waleed Y. Kadro, MD, and colleagues from the Golden Cardiovascular Center in Damascus, Syrian Arab Republic.

Kadro and colleagues calculated the TIMI frame count in the culprit artery after successful primary PCI in 44 patients who presented to their center with acute MI. The mean door to balloon time was 98 minutes, and all patients received 325 mg of aspirin and 600 mg loading dose of clopidogrel.

The researches reported that 21 patients (group one) were on statin therapy before admission, and the other 23 patients (group two) were not receiving statins.

The mean corrected TIMI frame count in the culprit artery post PCI was 18.34 frames in group one and 29.73 in group two, according to Kadro and colleagues.

Kadro and colleagues found that pretreatment with statins gives faster flow after successful primary PCI in acute MI.  They attributed the success of statins to their ability to cause improvement in endothelial dysfunction, decreased production of free radicals, reduced platelet aggregation, reduced production of inflammatory mediators and adhesion molecules. 

Overall, the researchers’ findings indicate that clopidogrel pretreatment abolishes the increase of PAI-1 active antigens coronary stent implantation, reduces ischemic outcomes following PCI and fosters faster TIMI flow after primary PCI. Other studies presented at ACC08 also encouraged the use of clopidogrel pretreatment for different clinical benefits.