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Clopidogrel response decreased with chronic renal failure

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Chronic renal disease appears to reduce platelet responsiveness to clopidogrel, according to a Korean research team.

Furthermore, increasing the dose of clopidogrel does not improve platelet responsiveness in these patients.

In their report in the November 1st issue of the American Journal of Cardiology, Dr. Weon Kim, at Kyung Hee University Medical Center in Seoul, and associates suggest that “the mechanisms for platelet dysfunction in patients with chronic renal failure include an increase in the platelet turnover rate, poor bioavailabilities such as disturbances of absorption or drug transportation, and coagulation disorders.”

The researchers compared platelet responsiveness to clopidogrel after coronary angiography or coronary or peripheral vascular intervention in patients with and without chronic renal failure. All patients except two in the renal failure group were men. Their average age was roughly 60 years.

The 23 patients with normal renal function were given 75 mg of clopidogrel per day. The 36 with chronic renal failure were randomized to receive either 75 mg or 100 mg of clopidogrel per day.

After 4 weeks, blood was drawn to measure platelet aggregation by analyzing the degree of light penetration.

The mean platelet inhibition was 35.2% among those with normal renal function, 21.3% among the renal failure patients on 75 mg of clopidogrel, and 23.4% among those on 150 mg (p = 0.026). The corresponding mean values of platelet aggregation in P2Y12 assay reaction units were 239.9, 308.7, and 302.7 (p = 0.013).

There was no significant difference in either measure between the two renal failure groups.

The authors note that decreased renal function is a risk factor for thrombosis of drug-eluting stents. “Clopidogrel resistance might be an important mechanism for the high occurrence of stent thrombosis in patients with chronic renal failure,” they point out.

“Drug-eluting stents should be (used cautiously) in patients with chronic renal failure,” Dr. Kim and associates conclude.

The investigators caution that their study was small, that variables other than platelet responsiveness were not investigated, and that their results cannot be generalized to women.

Am J Cardiol 2009;104:1292-1295.