Certoparin vs Unfractionated Heparin to Prevent VTEs in HF
Certoparin vs Unfractionated Heparin to Prevent VTEs in HF
Background Despite the elevated risk for developing venous thromboembolic events in patients with heart failure, there are no randomized, double-blind, controlled trial data on the comparison of low-molecular-weight heparin with unfractionated heparin (UFH) in this patient population.
Methods This was a subgroup analysis of the CERTIFY trial, which included 3,239 nonsurgical, acutely ill medical patients 70 years or older. Patients were randomized to receive 3,000-U anti-Xa certoparin once daily or 5,000-IU UFH 3 times a day. The analysis was performed on a subgroup of 542 patients diagnosed with heart failure at hospital admission.
Results Patients with heart failure differed from patients without heart failure in that they were more likely using antiplatelets (67.2% vs 48.9%; P < .0001) and had a lower glomerular filtration rate (8.0% vs 5.5%; ≤30 mL/min per 1.73 m; P = .0232). Thromboembolic risk was comparable except for a higher incidence of distal deep venous thrombosis (DVT) in patients with heart failure (10.80% vs 7.26%; P = .0144). Within the heart failure population, patient characteristics were comparable between randomized treatment groups. The incidence of the primary end point (proximal DVT, symptomatic nonfatal pulmonary embolism, and venous thromboembolism–related death combined) was numerically, slightly smaller with certoparin (3.78% vs 4.74% with UFH; odds ratio 0.79, 95% CI 0.32-1.94), and the incidence of major bleeding was 0.72% with certoparin versus 0.38% with UFH.
Conclusions Patients hospitalized for heart failure are at high risk for developing distal DVT and bleeding complications compared with acutely ill medical patients without heart failure. Within the heart failure population, the observed differences in prophylactic efficacy between 3,000-U anti-Xa certoparin once daily and 5,000-IU UFH 3 times a day were similar to those observed in the overall study population; this suggests that certoparin might be at least as effective as UFH also in this subgroup. There were no relevant differences in bleeding risk or frequency of adverse events.
Among the hospitalized medical patients, those with heart failure are at a particularly high risk for venous thromboembolism (VTE). Proposed additional thromboembolic risk factors in patients with heart failure are aberrant blood flow dynamics (dilated cardiac chambers, wall motion abnormalities, poor contractility, and in some cases atrial fibrillation), a hypercoagulable state, and an abnormal endocardial surface. In addition to this, more general risk factors for VTE such as advanced age, placement of a central venous or pulmonary artery catheter, obesity, and reduced mobility are frequent comorbid conditions. Both low-molecular-weight heparins (LMWHs) and unfractionated heparins (UFHs) are recommended for thromboprophylaxis in these patients by the recent American College of Chest Physicians guidelines.
In deciding whether to use LMWH or UFH, LMWHs are frequently preferred over UFH because of their improved bioavailability, reduced risk of heparin-induced thrombocytopenia (HIT), a prolonged predictable anticoagulant response, and once-daily subcutaneous administration. There is, however, no specific double-blind, randomized, head-to-head comparison of LMWH and UFH in this patient population, although heart failure is a frequent medical condition in placebo-controlled trials such as MEDENOX, PREVENT, and ARTEMIS (25%-52%) and in trials versus UFH (13%-50%). The only specific analysis on patients with heart failure has been conducted in the open PRINCE study, which demonstrated that 40-mg enoxaparin once daily was at least as effective as UFH.
Prompted by the need for more specific data on the efficacy and safety of LMWH versus UFH in this quantitatively important high-risk patient group, we prespecified a subgroup analysis of the randomized, double-blind CERTIFY study. CERTIFY has demonstrated noninferiority of the LMWH 3,000-U anti-Xa certoparin once daily versus 5,000-IU UFH 3 times a day for the prophylaxis of VTE in acutely ill, nonsurgical patients 70 years or older. More specifically, we aimed to compare patient groups with or without heart failure with respect to thromboembolic risk and bleeding complications during heparin use and to compare the efficacy and safety of certoparin and UFH in the subgroup of patients with heart failure.
Abstract and Introduction
Abstract
Background Despite the elevated risk for developing venous thromboembolic events in patients with heart failure, there are no randomized, double-blind, controlled trial data on the comparison of low-molecular-weight heparin with unfractionated heparin (UFH) in this patient population.
Methods This was a subgroup analysis of the CERTIFY trial, which included 3,239 nonsurgical, acutely ill medical patients 70 years or older. Patients were randomized to receive 3,000-U anti-Xa certoparin once daily or 5,000-IU UFH 3 times a day. The analysis was performed on a subgroup of 542 patients diagnosed with heart failure at hospital admission.
Results Patients with heart failure differed from patients without heart failure in that they were more likely using antiplatelets (67.2% vs 48.9%; P < .0001) and had a lower glomerular filtration rate (8.0% vs 5.5%; ≤30 mL/min per 1.73 m; P = .0232). Thromboembolic risk was comparable except for a higher incidence of distal deep venous thrombosis (DVT) in patients with heart failure (10.80% vs 7.26%; P = .0144). Within the heart failure population, patient characteristics were comparable between randomized treatment groups. The incidence of the primary end point (proximal DVT, symptomatic nonfatal pulmonary embolism, and venous thromboembolism–related death combined) was numerically, slightly smaller with certoparin (3.78% vs 4.74% with UFH; odds ratio 0.79, 95% CI 0.32-1.94), and the incidence of major bleeding was 0.72% with certoparin versus 0.38% with UFH.
Conclusions Patients hospitalized for heart failure are at high risk for developing distal DVT and bleeding complications compared with acutely ill medical patients without heart failure. Within the heart failure population, the observed differences in prophylactic efficacy between 3,000-U anti-Xa certoparin once daily and 5,000-IU UFH 3 times a day were similar to those observed in the overall study population; this suggests that certoparin might be at least as effective as UFH also in this subgroup. There were no relevant differences in bleeding risk or frequency of adverse events.
Introduction
Among the hospitalized medical patients, those with heart failure are at a particularly high risk for venous thromboembolism (VTE). Proposed additional thromboembolic risk factors in patients with heart failure are aberrant blood flow dynamics (dilated cardiac chambers, wall motion abnormalities, poor contractility, and in some cases atrial fibrillation), a hypercoagulable state, and an abnormal endocardial surface. In addition to this, more general risk factors for VTE such as advanced age, placement of a central venous or pulmonary artery catheter, obesity, and reduced mobility are frequent comorbid conditions. Both low-molecular-weight heparins (LMWHs) and unfractionated heparins (UFHs) are recommended for thromboprophylaxis in these patients by the recent American College of Chest Physicians guidelines.
In deciding whether to use LMWH or UFH, LMWHs are frequently preferred over UFH because of their improved bioavailability, reduced risk of heparin-induced thrombocytopenia (HIT), a prolonged predictable anticoagulant response, and once-daily subcutaneous administration. There is, however, no specific double-blind, randomized, head-to-head comparison of LMWH and UFH in this patient population, although heart failure is a frequent medical condition in placebo-controlled trials such as MEDENOX, PREVENT, and ARTEMIS (25%-52%) and in trials versus UFH (13%-50%). The only specific analysis on patients with heart failure has been conducted in the open PRINCE study, which demonstrated that 40-mg enoxaparin once daily was at least as effective as UFH.
Prompted by the need for more specific data on the efficacy and safety of LMWH versus UFH in this quantitatively important high-risk patient group, we prespecified a subgroup analysis of the randomized, double-blind CERTIFY study. CERTIFY has demonstrated noninferiority of the LMWH 3,000-U anti-Xa certoparin once daily versus 5,000-IU UFH 3 times a day for the prophylaxis of VTE in acutely ill, nonsurgical patients 70 years or older. More specifically, we aimed to compare patient groups with or without heart failure with respect to thromboembolic risk and bleeding complications during heparin use and to compare the efficacy and safety of certoparin and UFH in the subgroup of patients with heart failure.
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