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ATLANTA, Georgia — Patients with atrial fibrillation
receiving anticoagulant therapy are more likely to experience
gastrointestinal
(GI) bleeding when treated with rivaroxaban than when
treated with warfarin, according to a new analysis of data from
ROCKET AF.
Christopher Nessel, MD, from research and development at Johnson & Johnson in Raritan, New Jersey, reported the findings here at CHEST 2012: American College of Chest Physicians Annual Meeting.
"Compared with warfarin, the risk of GI bleeding is increased with rivaroxaban, but the incidence of life-threatening or fatal GI bleeding is lower," Dr. Nessel told Medscape Medical News. "A careful benefit/risk assessment is needed prior to prescribing rivaroxaban for high-risk patients," he added.
The analysis examined the incidence and outcomes of GI hemorrhage in 14,264 patients with nonvalvular atrial fibrillation enrolled in ROCKET AF.
The patients were randomized to either rivaroxaban or dose-adjusted warfarin. All GI bleeding events were recorded during treatment and for 2 days after the last dose was administered. Severity of bleeding was defined by a corresponding drop in hemoglobin or transfusion of more than 2 units of red cells.
The composite principal safety end point for GI bleeding events (upper GI, lower GI, and rectal bleeding) occurred more frequently in the 394 patients receiving rivaroxaban than in the 290 receiving warfarin (3.61% vs 2.60% per year; hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.19 to 1.61). Major bleeding was more frequent with rivaroxaban than with warfarin (2.00% vs 1.24% per year; HR, 1.61; 95% CI, 1.30 to 1.99), as was clinically relevant nonmajor bleeding (1.75% vs 1.39% per year; HR, 1.26; 95% CI, 1.20 to 1.55).
Patients who experienced major GI bleeding were more likely to have experienced GI bleeding in the past, to have mild anemia, to have a lower creatinine clearance, to be previous or current smokers, and to be older than patients who did not experience a GI bleeding during the trial (n = 13,552). They were also less likely to be female and to have previously experienced a stroke or transient ischemic attack.
The incidence of severe bleeding (transfusion of at least 4 units) was similar in the rivaroxaban and warfarin groups (49 vs 47). Six patients developed fatal bleeding: 1 in the rivaroxaban group and 5 in the warfarin group.
Data May Give Clinicians Pause When Considering Rivaroxaban
"The data presented extend the observations from the ROCKET AF clinical study," Dr. Nessel said. "Specifically, the analyses identified characteristics of nonvalvular atrial fibrillation patients that may predispose them to the occurrence of GI hemorrhage. The data also indicated that the overall fatality rates for bleeds of this nature are very low."
Independent commentator James Wisler, MD, from the division of cardiovascular disease at Duke University Medical Center in Durham, North Carolina, pointed out that this study underscores the importance of critically evaluating these newer anticoagulants when considering their use in a given patient.
"The decision regarding which anticoagulant to use for a given patient is complex, and risks and benefits need to be considered thoughtfully," he told Medscape Medical News. He added that the results of this study might give some physicians pause about initiating a newer anticoagulant, such as rivaroxaban, in a given patient with atrial fibrillation and an unfavorable risk profile, such as those with a previous GI bleed.
"While the previously published results from ROCKET AF suggested that the risk profiles were similar between rivaroxaban and warfarin, these results demonstrate that there is indeed a subpopulation of patients who may be better served with warfarin than rivaroxaban," he explained.
According to Dr. Wisler, both this analysis and the initial ROCKET AF study demonstrate that rivaroxaban is associated with fewer episodes of severe or fatal bleeding events, despite the increase in major and clinically relevant nonmajor bleeding observed in the specific subgroup of this study. "Currently, it is unclear why this discrepancy exists," he added.
He recommends that clinicians take a careful patient history to assess bleeding risk factors when considering the initiation of a newer anticoagulant such as rivaroxaban.
"While perhaps more convenient and efficacious, certain patient populations, such as that evaluated in this study, may receive net harm from these newer agents," he said.
The study authors report multiple financial relationships with the following companies: AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Eli Lilly, GSK, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, sanofi-aventis, Schering-Plough, The Medicines Company, Ortho/McNeill, Pfizer, Polymedix, Boston Scientific, Medtronic, Forest Laboratories, Janssen Research and Development, and Genzyme. Dr. Wisler has disclosed no relevant financial relationships.source medscape
Christopher Nessel, MD, from research and development at Johnson & Johnson in Raritan, New Jersey, reported the findings here at CHEST 2012: American College of Chest Physicians Annual Meeting.
"Compared with warfarin, the risk of GI bleeding is increased with rivaroxaban, but the incidence of life-threatening or fatal GI bleeding is lower," Dr. Nessel told Medscape Medical News. "A careful benefit/risk assessment is needed prior to prescribing rivaroxaban for high-risk patients," he added.
The analysis examined the incidence and outcomes of GI hemorrhage in 14,264 patients with nonvalvular atrial fibrillation enrolled in ROCKET AF.
The patients were randomized to either rivaroxaban or dose-adjusted warfarin. All GI bleeding events were recorded during treatment and for 2 days after the last dose was administered. Severity of bleeding was defined by a corresponding drop in hemoglobin or transfusion of more than 2 units of red cells.
The composite principal safety end point for GI bleeding events (upper GI, lower GI, and rectal bleeding) occurred more frequently in the 394 patients receiving rivaroxaban than in the 290 receiving warfarin (3.61% vs 2.60% per year; hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.19 to 1.61). Major bleeding was more frequent with rivaroxaban than with warfarin (2.00% vs 1.24% per year; HR, 1.61; 95% CI, 1.30 to 1.99), as was clinically relevant nonmajor bleeding (1.75% vs 1.39% per year; HR, 1.26; 95% CI, 1.20 to 1.55).
Patients who experienced major GI bleeding were more likely to have experienced GI bleeding in the past, to have mild anemia, to have a lower creatinine clearance, to be previous or current smokers, and to be older than patients who did not experience a GI bleeding during the trial (n = 13,552). They were also less likely to be female and to have previously experienced a stroke or transient ischemic attack.
The incidence of severe bleeding (transfusion of at least 4 units) was similar in the rivaroxaban and warfarin groups (49 vs 47). Six patients developed fatal bleeding: 1 in the rivaroxaban group and 5 in the warfarin group.
Data May Give Clinicians Pause When Considering Rivaroxaban
"The data presented extend the observations from the ROCKET AF clinical study," Dr. Nessel said. "Specifically, the analyses identified characteristics of nonvalvular atrial fibrillation patients that may predispose them to the occurrence of GI hemorrhage. The data also indicated that the overall fatality rates for bleeds of this nature are very low."
Independent commentator James Wisler, MD, from the division of cardiovascular disease at Duke University Medical Center in Durham, North Carolina, pointed out that this study underscores the importance of critically evaluating these newer anticoagulants when considering their use in a given patient.
"The decision regarding which anticoagulant to use for a given patient is complex, and risks and benefits need to be considered thoughtfully," he told Medscape Medical News. He added that the results of this study might give some physicians pause about initiating a newer anticoagulant, such as rivaroxaban, in a given patient with atrial fibrillation and an unfavorable risk profile, such as those with a previous GI bleed.
"While the previously published results from ROCKET AF suggested that the risk profiles were similar between rivaroxaban and warfarin, these results demonstrate that there is indeed a subpopulation of patients who may be better served with warfarin than rivaroxaban," he explained.
According to Dr. Wisler, both this analysis and the initial ROCKET AF study demonstrate that rivaroxaban is associated with fewer episodes of severe or fatal bleeding events, despite the increase in major and clinically relevant nonmajor bleeding observed in the specific subgroup of this study. "Currently, it is unclear why this discrepancy exists," he added.
He recommends that clinicians take a careful patient history to assess bleeding risk factors when considering the initiation of a newer anticoagulant such as rivaroxaban.
"While perhaps more convenient and efficacious, certain patient populations, such as that evaluated in this study, may receive net harm from these newer agents," he said.
The study authors report multiple financial relationships with the following companies: AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Eli Lilly, GSK, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, sanofi-aventis, Schering-Plough, The Medicines Company, Ortho/McNeill, Pfizer, Polymedix, Boston Scientific, Medtronic, Forest Laboratories, Janssen Research and Development, and Genzyme. Dr. Wisler has disclosed no relevant financial relationships.source medscape
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