In patients undergoing fibrinolytic therapy for ST-elevation MI, higher baseline neutrophil counts are associated with worse angiographic findings and higher mortality, according to a report. In patients undergoing fibrinolytic therapy for ST-elevation myocardial infarction (STEMI), higher baseline neutrophil counts are associated with worse angiographic findings, higher mortality, and a diminished response to clopidogrel, according to a report in the April European Heart Journal.

"We were initially surprised to see that those patients with a lower baseline neutrophil count were those who appeared to have the greater benefit from adjunctive therapy with clopidogrel," Dr. Michelle O'Donoghue from Brigham and Women's Hospital, Boston told Reuters Health. "This finding is not immediately intuitive since pathways between thrombosis and inflammation are widely overlapping."

The study involved 2865 patients with STEMI, the authors report. Baseline neutrophil count was directly related to the risk of cardiovascular death in the first 30 days, ranging from 1.4 per cent for patients with neutrophil counts in the lowest quartile to 7.4 per cent for those in the highest quartile.

Higher baseline neutrophil counts were also independently associated with significantly higher risk of congestive heart failure, lower likelihood of complete ST-segment resolution following fibrinolytic therapy, and lower odds of myocardial microvascular perfusion at the time of angiography.

Patients with baseline neutrophil counts above the median derived less benefit from clopidogrel treatment than did those with lower neutrophil counts, the investigators say. Clopidogrel reduced the odds of the primary composite endpoint (TIMI flow grade 0/1, or death or MI prior to angiography) by 54 per cent in patients with lower neutrophil counts, but only by 17 per cent in patients with higher neutrophil counts.

"We believe the current analysis confirms a strong and independent association between neutrophil count and the risk of death and CHF in a very large population of patients with STEMI undergoing fibrinolysis," Dr. O'Donoghue said. "The current study also provided us with the unique opportunity to examine the association between cell count and angiographic outcomes in the largest angiographic dataset for this study population to date."

"The interaction with clopidogrel is hypothesis-generating and will require validation in future prospective trials," Dr. O'Donoghue added. "However the findings do reinforce the central role of inflammation in atherothrombosis and lend further support to therapies that target leukocytes in patients with acute coronary syndromes."

"We intend to examine the association between neutrophil count and clinical and angiographic outcomes in existing and ongoing trial populations, as well as to examine possible treatment interaction with randomized therapies," Dr. O'Donoghue said.

Eur Heart J 2008;29:984-991