NEW ORLEANS — Measuring high-sensitivity C-reactive protein prior to elective percutaneous coronary intervention may be useful for identifying the subset of patients who will derive greatest benefit from long-term clopidogrel, Steven R. Steinhubl, M.D., reported at the annual scientific sessions of the American Heart Association.
He presented a secondary analysis involving the 1,469 participants in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial for whom baseline C-reactive protein (CRP) values were available. The subanalysis showed that an elevated CRP level prior to percutaneous intervention (PCI) was an independent predictor of poor outcome at 1-year follow-up—and that a full year of clopidogrel in such patients markedly reduced their risk of atherosclerotic events, compared with just a month of clopidogrel immediately post PCI.
CREDO was a double-blind clinical trial involving more than 2,100 patients who underwent planned elective PCI. They were randomized to receive a pre-PCI loading dose of 300 mg clopidogrel or placebo. Afterward, all patients received 75 mg/day of clopidogrel for 28 days. Thereafter out to 12 months, patients who had gotten the loading dose of clopidogrel continued on 75 mg/day of the antiplatelet agent, while those in the control arm got placebo. All CREDO participants also received the standard 75 mg/day of aspirin during the follow-up period.
Previously reported primary results of CREDO showed that patients who received a year of clopidogrel had a statistically significant 27% reduction in the combined end point of death, MI, or urgent target vessel revascularization (JAMA 2002;288:2411-20). The new subanalysis was conducted to see whether CRP could be utilized to target long-term clopidogrel therapy more precisely, explained Dr. Steinhubl, CREDO principal investigator and a cardiologist at the University of Kentucky, Lexington.
This indeed proved to be the case. Patients in the highest baseline tertile for CRP—those with a CRP level higher than 5.1 mg/L—had a 15% incidence of the combined end point of death, MI, or stroke at 1 year if they received only 1 month of clopidogrel followed by placebo after PCI. The incidence of the combined end point dropped to 8% in highest-tertile CRP patients who got a full year of the antiplatelet agent, a 44% reduction in relative risk.
An elevated CRP level is conventionally defined as higher than 3 mg/L. Among the 704 CREDO participants known to have CRP levels higher than this threshold pre-PCI, the 1-year rate of the combined end point was 9% in those who received long-term clopidogrel, a highly significant 36% reduction in risk compared with the 14% incidence in the group who got a month of clopidogrel.
Although these data are promising, Dr. Steinhubl noted the findings require replication, as this was a post hoc analysis.
In another CREDO substudy presented at the conference, W.H. Wilson Tang, M.D., reported that pre-PCI plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were useful in stratifying patients in terms of risk of atherosclerotic events at 1 year. Even NT-proBNP levels that were lower than the standard diagnostic threshold for heart failure were associated with increased risk independent of left ventricular ejection fraction.
“These data support the notion that the prognostic value of NT-proBNP in patients with coronary ischemia may not necessarily be specific to the setting of acute coronary syndrome,” observed Dr. Tang of the Cleveland Clinic Foundation.
CREDO participants in the lowest tertile for NT-proBNP levels—52 pg/mL or lower—had a 4.8% incidence of the combined end point of death, MI, or stroke at 1 year. The incidence climbed in stepwise fashion with increasing BNP. Patients with a BNP level of 53-130 pg/mL had an 8.3% event rate, those in the 131-340 pg/mL range had a 9.6% event rate, and those in the highest BNP tertile had a 16% event rate. The standard diagnostic threshold for heart failure using this commercial assay is 125 pg/mL.
The substudy received no commercial funding. The main CREDO trial was sponsored by Sanofi-Synthelabo.
