High Loading Dose of Clopidogrel Cuts Occurrence of MIs During Intervention


ORLANDO, FLA. — A 600-mg loading dose of clopidogrel was safe and more effective than the standard 300-mg dose prior to percutaneous coronary intervention in a study with 255 patients.

“Pretreatment with a 600-mg loading dose of clopidogrel given 6 hours before a percutaneous revascularization procedure reduced periprocedural myocardial infarctions and improved short-term prognosis,” Germano Di Sciascio, M.D., said at the annual meeting of the American College of Cardiology.

“This is the first study to compare a 600-mg loading dose of clopidogrel with any other dose based on clinical outcomes, and the results are sufficient to change clinical practice,” commented Peter Berger, M.D., director of interventional catheterization at Duke University Medical Center, Durham, N.C.

Many physicians already use a 600-mg loading dose, especially for high-risk patients, because it produces quicker and more complete inhibition of platelet activity, noted Dr. Di Sciascio, professor of medicine and chairman of the department of cardiology at the University of Rome. But until now, the safety and efficacy of this dose had not been proven in a clinical study, and official guidelines had continued to endorse a 300-mg loading dose.

The Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty (ARMYDA-2) study enrolled patients with effort angina and a positive stress test result or a recent ST-segment elevation acute MI who were scheduled to undergo coronary angiography. All patients underwent catheterization at either of two Italian hospitals: the Campus Bio-Medico of the University of Rome, or the Vito Fazzi Hospital in Lecce. The study received no external funding. Of 329 patients who had angiography, 255 had significant coronary artery disease and went on to have a percutaneous intervention.

An average of 6 hours before revascularization, patients were treated with either a 300-mg or 600-mg dose of clopidogrel. All patients also received aspirin and a weight-adjusted regimen of intravenous heparin. Treatment with a glycoprotein IIb/IIIa receptor antagonist could also be used at the operator's discretion. Following each procedure, all patients continued to receive a standard, daily regimen of aspirin and clopidogrel.

The study's primary end point was the combined rate of death, MI, and target-vessel revascularization at 30 days after the procedure. MI was defined as a postprocedural elevation of serum creatine kinase-MB (CK-MB) to more than three times the upper limit of normal.

This end point was reached in 4% of patients who received a 600-mg loading dose, compared with 12% of patients who received a 300-mg loading dose, a statistically significant difference. There were no deaths. One patient who received the 600-mg dose required revascularization, and five patients in the 600-mg group had an MI. A total of 15 patients in the 300-mg group had an MI.

Several secondary end points also favored the higher loading dose, including any rise in CK-MB above the upper limit of normal, and an increase in troponin I levels.

No patient in the study had a major bleed or needed a transfusion following revascularization.

In a multivariable analysis that controlled for possible confounding factors such as stent length, use of a IIb/IIIa inhibitor, and use of a statin starting before the procedure, treatment with the higher clopidogrel loading dose cut the incidence of periprocedural MI by 52%. Pretreatment with a statin was also associated with a significant 72% reduction in MIs. The effect of statin pretreatment and the 600-mg loading dose was additive: Patients who received both had an 80% reduced risk of a periprocedural MI, Dr. Di Sciascio said.

Recommended Reading

TPA Safe, Effective for Stroke After Cardiac Cath
MDedge Cardiology
Advances in Imaging Renew Interest in Carotid Bypass Surgery
MDedge Cardiology
Neurology Coalition Sets Carotid Stent Standards
MDedge Cardiology
Pulmonary Artery Cath Ineffective in Heart Failure
MDedge Cardiology
Use of Morphine for MI Questioned
MDedge Cardiology
Why Renal Failure Patients With MI Have 'Dismal' Outcomes
MDedge Cardiology
Women Show More Post-MI Depression
MDedge Cardiology
Uses for Drug-Eluting Stents Are Rising Rapidly
MDedge Cardiology
Sirolimus-Eluting Stents Edge Past Paclitaxel Stents
MDedge Cardiology
Warfarin Less Effective in Real Life Than in Trials
MDedge Cardiology