Combination anticoagulation therapy doubles risk of bleeding in patients at high risk of stroke
http://www.100md.com
《英国医生杂志》
Patients at high risk of stroke should not be treated with combination anticoagulation therapy using aspirin and clopidogrel—known to be beneficial for those with cardiovascular disease—because it doubles the risk of bleeding, concludes new research from the University of Essen, Germany (Lancet 2004;364:331-7).
Previous research showed that clopidogrel was better than aspirin for patients who had recently had an ischaemic stroke, heart attack, or symptomatic peripheral arterial disease. Its benefits were greater in some high risk subgroups of patients, such as those with diabetes or previous cardiac surgery (Lancet 1996;348:1329-39).
The current findings are based on a randomised, double blind, placebo controlled trial, which included 7599 high risk patients from 507 stoke units and neurology departments in 28 countries.
The patients were already taking clopidogrel for either an ischaemic stroke or a transient ischaemic attack that they had had within the preceding three months. They also had at least one or more of five additional vascular risk factors: a history of stroke or heart attack, angina pectoris, diabetes mellitus, or symptomatic peripheral vascular disease.
They were randomly assigned to either aspirin (75 mg a day) or placebo, and they all also received clopidogrel (75 mg a day); the study treatment lasted for 18 months.
Patients taking aspirin and clopidogrel had a small but non-significant reduction in major vascular events (defined by the study as being a composite of heart attack, ischaemic stroke, death from vascular causes, and readmission to hospital for acute ischaemia, including transient ischaemic attack, angina, and worsening peripheral arterial vascular disease) (relative risk reduction 6.4%, 95% confidence interval - 4.6 to 16.3, P=0.244; absolute risk reduction 1%, - 0.6 to 2.7, P=0.244).
But they also had double the absolute risk of intracranial and gastrointestinal bleeding—2.6% v 1.3%—compared with those taking clopidogrel alone (absolute risk increase 1.3%, 0.6 to 1.9, P<0.0001), thus offsetting any potential benefit of combination treatment. The risk of serious bleeding was also increased among those taking the combination treatment.
The use of combination anticoagulation therapy in patients at low risk of transient ischaemic attack or ischaemic stroke is currently being investigated in a further trial.
In a comment article in the same issue of the Lancet (p 305-6), Dr Peter Rothwell from the stroke prevention research unit at the University of Oxford said that the study had shown that "compared with clopidogrel alone, the risk of major bleeding with the addition of aspirin outweighs any benefit at 18 months." He added: "Patients with previous transient ischaemic attacks or stoke who are currently taking aspirin and clopidogrel should be advised of the risk."(London Debashis Singh)
Previous research showed that clopidogrel was better than aspirin for patients who had recently had an ischaemic stroke, heart attack, or symptomatic peripheral arterial disease. Its benefits were greater in some high risk subgroups of patients, such as those with diabetes or previous cardiac surgery (Lancet 1996;348:1329-39).
The current findings are based on a randomised, double blind, placebo controlled trial, which included 7599 high risk patients from 507 stoke units and neurology departments in 28 countries.
The patients were already taking clopidogrel for either an ischaemic stroke or a transient ischaemic attack that they had had within the preceding three months. They also had at least one or more of five additional vascular risk factors: a history of stroke or heart attack, angina pectoris, diabetes mellitus, or symptomatic peripheral vascular disease.
They were randomly assigned to either aspirin (75 mg a day) or placebo, and they all also received clopidogrel (75 mg a day); the study treatment lasted for 18 months.
Patients taking aspirin and clopidogrel had a small but non-significant reduction in major vascular events (defined by the study as being a composite of heart attack, ischaemic stroke, death from vascular causes, and readmission to hospital for acute ischaemia, including transient ischaemic attack, angina, and worsening peripheral arterial vascular disease) (relative risk reduction 6.4%, 95% confidence interval - 4.6 to 16.3, P=0.244; absolute risk reduction 1%, - 0.6 to 2.7, P=0.244).
But they also had double the absolute risk of intracranial and gastrointestinal bleeding—2.6% v 1.3%—compared with those taking clopidogrel alone (absolute risk increase 1.3%, 0.6 to 1.9, P<0.0001), thus offsetting any potential benefit of combination treatment. The risk of serious bleeding was also increased among those taking the combination treatment.
The use of combination anticoagulation therapy in patients at low risk of transient ischaemic attack or ischaemic stroke is currently being investigated in a further trial.
In a comment article in the same issue of the Lancet (p 305-6), Dr Peter Rothwell from the stroke prevention research unit at the University of Oxford said that the study had shown that "compared with clopidogrel alone, the risk of major bleeding with the addition of aspirin outweighs any benefit at 18 months." He added: "Patients with previous transient ischaemic attacks or stoke who are currently taking aspirin and clopidogrel should be advised of the risk."(London Debashis Singh)