Tailored Drug Delivery Reduces Adverse Effects After PCI

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Individually tailored anti-clotting medication dosing significantly cut the rate of adverse events after non-emergent percutaneous coronary intervention (PCI) with stenting, researchers reported at the American Heart Association’s Scientific Sessions 2008. Results of the Tailored Clopidogrel Loading Dose According to Platelet Reactivity Monitoring to Prevent Stent Thrombosis study were presented as a late-breaking clinical trial.

The formation of blood clots within a stent (stent thrombosis) is an important concern after PCI with coronary stenting placement to open narrowed coronary arteries.

Clopidogrel is a drug that reduces blood platelets’ tendency to clot in response to injury, such as the stretching of the blood vessels during PCI. However, individuals respond differently to the drug, with a significant number deemed “low responders,” those having a reduced response to the drug.

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That led to the hypothesis that an individualized approach might magnify the benefits of clopidogrel, said Franck Paganelli, M.D., Ph.D., author of the study and professor of medicine in the division of cardiology, Hopital Nord (North Hospital), University of Marseille, School of Medicine, Marseille, France.

The researchers studied 429 low responders, including 214 in the control group who got usual care with one 600 milligram (mg) dose of clopidogrel. The test group received up to three more doses of clopidogrel every 24 hours with a goal of reducing their score to the cut-off level on a VASP phosphorylation analysis, a blood test that measures a patient’s anti-platelet response to clopidogrel.

The primary endpoint was the rate of early definite stent thrombosis. That was defined as a total blockage or visible thrombus originating in or within 5 millimeters (mm) of the stent and associated with symptoms or diagnostic signs of reduced blood flow to the heart muscle within 48 hours of the procedure.

The secondary endpoints were the rate of a composite of major adverse cardiac events (MACE), which included myocardial infarction (heart attack) and cardiovascular death, or urgent revascularization procedures, as well as the separate endpoint of bleeding.

Despite additional doses of clopidogrel up to a total of 2400 mg, 8 percent of the low-responders remained with a low response. However, the tailored approach significantly lowered the primary and secondary event endpoints without significantly increasing bleeding events, said Paganelli. The rate of early definite stent thrombosis was 0.5 percent in the tailored-dosage patients versus 4.2 percent in the controls (p<0.01). The rate of MACE was substantially lower in the individualized treatment group: 0.5 percent vs. 8.9 percent for the controls.

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