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Coagulation activation and long-term outcome in acute coronary syndromes
Diego Ardissino1, Piera Angelica Merlini, Kenneth A Bauer
1Division of Cardiology, Ospedale Niguarda Ca' Grande, Milan, Italy.ardis001@planet.it
Insights
Following acute coronary syndrome, both high and low levels of thrombin generation predict worse outcomes. Intermediate thrombin generation levels are associated with the lowest risk of cardiac death or myocardial infarction.
Area of Science:
- Cardiology
- Hematology
- Biochemistry
Background:
- Patients with unstable angina or myocardial infarction often exhibit elevated thrombin generation.
- The long-term prognostic significance of this coagulation activation remains unclear.
Purpose of the Study:
- To investigate the relationship between persistently elevated thrombin generation and long-term outcomes in patients with acute coronary syndromes.
- To assess the predictive value of plasma prothrombin fragment 1 + 2 levels for adverse cardiac events.
Main Methods:
- Prospective multicenter cohort study of 319 patients from the GUSTO IIb trial.
- Measurement of plasma prothrombin fragment 1 + 2 levels during acute phase and at 1, 6, and 12 months.
- Median follow-up of 29 months to assess cardiac death or myocardial (re)infarction.
Main Results:
- The primary endpoint occurred in 19% of patients.
- A U-shaped relationship was observed between prothrombin fragment 1 + 2 levels and adverse outcomes.
- Both high (> 1.9 nM) and low (< 1.5 nM) levels were associated with increased risk (RR 1.56 and 1.35, respectively).
Conclusions:
- Persistently elevated thrombin generation after acute coronary syndrome is a predictor of unfavorable long-term outcomes.
- Both excessive and insufficient thrombin generation levels indicate increased risk.
- Optimal management may involve balancing coagulation activation levels.
Abstract:
After an episode of unstable angina or myocardial infarction, a high proportion of patients show biochemical signs of coagulation activation, expressed as persistently elevated thrombin generation, in their blood. It is not known whether this has any influence on long-term outcome. In this prospective multicenter cohort study, we assessed the relation of persistently elevated thrombin generation to outcome in 319 consecutive patients with acute coronary syndromes enrolled in the Global Use of Strategies To Open occluded coronary arteries (GUSTO) IIb trial. Plasma prothrombin fragment 1 + 2 levels, an index of "in vivo" thrombin generation, was measured during the acute phase and after 1, 6, and 12 months, and its relation to outcome was assessed during a median 29-month follow-up period. The primary end point of cardiac death or myocardial (re)infarction occurred in 61 patients (19%). There was a U-shaped relationship between plasma prothrombin fragment 1 + 2 levels and the risk of developing the primary end point; intermediate levels (1.5-1.9 nM) were associated with the lowest risk, whereas both higher (> 1.9 nM) and lower (< 1.5 nM) values were associated with an increased risk (relative risk [RR] 1.56 and 95% confidence interval [CI], 1.25-2.28; RR, 1.35 and 95% CI, 1.11-1.86, respectively). After an episode of acute coronary syndrome, both high and low levels of thrombin generation are predictors of an increased risk of an unfavorable outcome.