Genetic and Clinical Factors Linked to Stent Thrombosis

French researchers have identified several genetic and clinical factors independently tied to early stent thrombosis. In a report published in the Journal of the American Medical Association, Guillaume Cayla and colleagues performed a case-control study comparing 123 patients with definite early stent thrombosis with 246 matched controls without stent thrombosis.

The researchers found 3 genes with variants that significantly and independently raised the risk for early stent thrombosis:

  • CYP2C19,
  • ABCB1, and
  • ITGB3.

Independent clinical factors were:

  • acuteness of PCI,
  • complex lesions,
  • LV EF <40%,
  • diabetes,
  • proton pump inhibitor use, and
  • higher clopidogrel loading doses (inverse correlation).

The clinical and genetic models were about equal in their predictive power, but a combined model was significantly better than either alone.

Among the independent factors identified in the study the researchers noted that the 3 genes and two of the clinical factors (loading dose and PPI use) were related to clopidogrel. They then called for future studies to determine “whether treatment adjustment on the basis of such global risk stratification can improve the prognosis of patients undergoing PCI.”

Here is the press release from JAMA:

Researchers Identify Factors Associated With Increased Risk of Blood Clot Within Coronary Stent

CHICAGO – Patients with certain genes or specific factors related to use of the anti-clotting drug clopidogrel are more likely to experience a blood clot within a coronary stent shortly after placement, according to a study in the October 26 issue ofJAMA.

“Percutaneous coronary intervention [PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries] with stent implantation has become the standard of care for myocardial revascularization, especially in the setting of unstable coronary artery disease. Despite the use of dual antiplatelet therapy (DAPT; aspirin and clopidogrel), which reduces cardiovascular events after PCI by more than 80 percent, definite stent thrombosis [blood clot] remains a concern,” according to background information in the article. Stent thrombosis can be a devastating (mortality rate up to 40 percent) and unpredictable complication of PCI. The majority of stent thromboses occur in the first month after placement and are defined as early stent thrombosis.

Guillaume Cayla, M.D., Ph.D., of the Pitie-Salpetriere Hospital, Paris, and colleagues conducted an analysis of clinical and genetic factors associated with definite early stent thrombosis. The study, conducted in 10 centers in France between January 2007 and May 2010, included 123 patients undergoing PCI who had definite early stent thrombosis (within 30 days of stent implantation) and DNA samples available, matched on age and sex with 246 stent thrombosis-free controls. The primary outcome measured was the accuracy of prediction of early stent thrombosis with 23 genetic variants.

Multivariable analyses were performed to identify which clinical, angiographic, and genetic variables were independently associated with the occurrence of early stent thrombosis. Among the 23 genetic variants investigated in 15 different genes, the researchers found that 3 genotypes related to clopidogrel metabolism and platelet function (CYP2C19ABCB1, and ITGB3) were an independent risk factor for early stent thrombosis. The authors also identified 2 potentially modifiable factors of early stent thrombosis: clopidogrel loading dose and clopidogrel interaction with proton pump inhibitors. Patients in the highest tertile (one of three groups) of risk using a combined clinical and genetic model had a 7-fold increased risk of early stent thrombosis vs. patients in the lowest tertile.

“Our study adds to the understanding of the genetic profile of patients treated with clopidogrel who are at risk of early stent thrombosis,” the researchers write

“Combining genetic factors with clinical factors improved risk stratification for stent thrombosis. Whether treatment adjustment on the basis of such global risk stratification can improve the prognosis of patients undergoing PCI will require future validation in independent cohorts.”

(JAMA. 2011;306[16]:1765-1774)

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