AHJ: Bivalirudin alone associated with lower risk of acquired thrombocytopenia
Acquired thrombocytopenia occurs in approximately one in 14 patients with acute coronary syndromes (ACS) treated with anti-thrombin and antiplatelet medications and is strongly associated with hemorrhagic and ischemic complications, according to a post hoc analysis of the ACUITY trial. The study, published in the February issue of the American Heart Journal, also found that the administration of bivalirudin monotherapy appears to be associated with less frequent declines in platelet count, compared with an anticoagulant regimen including a GP IIb/IIIa inhibitor.
Current guidelines for patients with moderate- or high-risk ACS recommend early invasive management with concomitant antithrombotic therapy, including aspirin, clopidogrel, heparin plus GP IIb/IIIa inhibitors, or, as an alternative, bivalirudin (Angiomax, The Medicines Company). However, the study authors noted that antithrombotic therapy combination of heparin and GP IIb/IIIa inhibitor use may cause acquired thrombocytopenia and has been strongly associated with increased risks of hemorrhagic and ischemic complications, as well as early and late mortality.
“Although reversible, thrombocytopenia in this setting is associated with bleeding and ischemic complications, blood product transfusion and prolonged hospitalization,” the authors wrote.
Therefore, Adriano M. Caixeta, MD, PhD, from Columbia University Medical Center in New York City, and colleagues examined 10,836 patients with ACS randomized to receive heparin plus GP IIb/IIIa inhibitors, bivalirudin plus GP IIb/IIIa inhibitors or bivalirudin monotherapy.
They found that acquired thrombocytopenia developed in 6.8 percent of patients; mild (100,000-150,000 platelets/mm3), moderate (50,000-100,000 platelets/mm3) and severe (<50,000 platelets/mm3) developed in 6 percent, 0.5 percent and 0.3 percent of patients, respectively. Also, patients with acquired thrombocytopenia, compared with those without, were more likely to develop major bleeding (14 vs. 4.3 percent) at 30 days and had higher rates of mortality (6.5 vs. 3.4 percent) at one year.
Using a multivariate analysis, Caixeta and colleagues found that the acquired thrombocytopenia was an independent predictor of major bleeding at 30 days (hazard ratio [HR] 1.68). Moderate and severe acquired thrombocytopenia were predictors of mortality at one year (HR 2.89 and HR 3.41, respectively).
Importantly, compared with heparin plus GP IIb/IIIa inhibitors, bivalirudin monotherapy was associated with less declines in platelet count by more than 25 percent (7.6 vs. 5.6 percent) and more than 50 percent (1.4 vs. 0.7 percent) from baseline.
“These results, now reproduced in three consecutive large-scale randomized trials involving more than 20,000 patients (REPLACE-2, ACUITY and HORIZONS-AMI), demonstrate that bivalirudin monotherapy, compared with an anticoagulation regimen including a GP IIb/IIIa inhibitor, is associated with a significantly lower risk of acquired thrombocytopenia (relative acquired thrombocytopenia in the present study) and suggest that this may reduce the occurrence of both early and late mortality,” the authors concluded.
Current guidelines for patients with moderate- or high-risk ACS recommend early invasive management with concomitant antithrombotic therapy, including aspirin, clopidogrel, heparin plus GP IIb/IIIa inhibitors, or, as an alternative, bivalirudin (Angiomax, The Medicines Company). However, the study authors noted that antithrombotic therapy combination of heparin and GP IIb/IIIa inhibitor use may cause acquired thrombocytopenia and has been strongly associated with increased risks of hemorrhagic and ischemic complications, as well as early and late mortality.
“Although reversible, thrombocytopenia in this setting is associated with bleeding and ischemic complications, blood product transfusion and prolonged hospitalization,” the authors wrote.
Therefore, Adriano M. Caixeta, MD, PhD, from Columbia University Medical Center in New York City, and colleagues examined 10,836 patients with ACS randomized to receive heparin plus GP IIb/IIIa inhibitors, bivalirudin plus GP IIb/IIIa inhibitors or bivalirudin monotherapy.
They found that acquired thrombocytopenia developed in 6.8 percent of patients; mild (100,000-150,000 platelets/mm3), moderate (50,000-100,000 platelets/mm3) and severe (<50,000 platelets/mm3) developed in 6 percent, 0.5 percent and 0.3 percent of patients, respectively. Also, patients with acquired thrombocytopenia, compared with those without, were more likely to develop major bleeding (14 vs. 4.3 percent) at 30 days and had higher rates of mortality (6.5 vs. 3.4 percent) at one year.
Using a multivariate analysis, Caixeta and colleagues found that the acquired thrombocytopenia was an independent predictor of major bleeding at 30 days (hazard ratio [HR] 1.68). Moderate and severe acquired thrombocytopenia were predictors of mortality at one year (HR 2.89 and HR 3.41, respectively).
Importantly, compared with heparin plus GP IIb/IIIa inhibitors, bivalirudin monotherapy was associated with less declines in platelet count by more than 25 percent (7.6 vs. 5.6 percent) and more than 50 percent (1.4 vs. 0.7 percent) from baseline.
“These results, now reproduced in three consecutive large-scale randomized trials involving more than 20,000 patients (REPLACE-2, ACUITY and HORIZONS-AMI), demonstrate that bivalirudin monotherapy, compared with an anticoagulation regimen including a GP IIb/IIIa inhibitor, is associated with a significantly lower risk of acquired thrombocytopenia (relative acquired thrombocytopenia in the present study) and suggest that this may reduce the occurrence of both early and late mortality,” the authors concluded.