Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006 Apr 20;354(16):1706-1717.
Atherothrombotic disorders of the circulatory system are the leading cause of death and disability in the world. Low-dose aspirin has been shown to reduce ischemic event in populations above a certain risk threshold; however, aspirin alone may be insufficient treatment to prevent ischemic events in high-risk patients. Dual antiplatelet therapy with aspirin and clopidogrel has been shown to reduce ischemic events in patients with unstable angina, non-ST segment elevation and ST segment elevation myocardial infarction, as well as in those undergoing angioplasty and stenting.
This was a prospective, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of aspirin plus clopidogrel in comparison with aspirin plus placebo in patients at high risk for a cardiovascular event. Patients included in the study were 45 or older and had one of the following: multiple atherothrombotic risk factors, documented coronary artery disease, documented cerebrovascular disease, or documented symptomatic peripheral vascular disease. The primary efficacy endpoint was the first occurrence of myocardial infarction (MI), stroke, or death from cardiovascular causes. The primary safety endpoint was severe bleeding.
A total of 15,603 patients were enrolled in the study. Treatment was permanently discontinued by 20.4% in the clopidogrel group as compared with 18.2% in the placebo group (P<0.001). A total of 4.8% of patients in the clopidogrel group and 4.9% in the placebo group discontinued treatment because of an adverse event (P=0.67). Other than the treatment medications, concomitant medication use was similar in both groups. A median follow-up of 28 months revealed that the rates of primary efficacy events in the clopidogrel and placebo group were similar (6.8% versus 7.3%, P=0.22, respectively). The rate of primary safety events was 1.7% in the clopidogrel group and 1.3% in the placebo group, P=0.09.
This trial enrolled patients who either had established atherothrombotic disease or were at high risk for such disease and found that there was no significant benefit associated with the use of clopidogrel plus aspirin compared to aspirin alone in reducing myocardial infarction, stroke, or cardiovascular death. The risk of moderate or severe bleeding in symptomatic patients was higher in the clopidogrel plus aspirin group than in the aspirin plus placebo group. Overall, these findings do not support the use of dual antiplatelet therapy across this broad patient population.
D-Dimer in the Diagnosis of Pulmonary Embolism
Kearon C, Ginsberg JS, Douketis J, et al. An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial. Ann Intern Med. 2006 Jun 6;144(11):812-821.
The clinical usefulness of the D-dimer test in the diagnosis of pulmonary embolism (PE) has been previously studied. In patients with suspected PE, it may be safe to omit additional diagnostic testing if a patient has a negative D-dimer test; however, this approach has never been evaluated in a randomized, controlled trial.
The investigators in this trial studied two subgroups of patients with suspected PE and a negative D-dimer: patients with a low clinical probability of PE and those with a moderate or high clinical probability of PE who had a non-diagnostic ventilation perfusion scan (VQ scan) and no proximal deep vein thrombosis on venous ultrasonography. The hypothesis was that patients with a negative D-dimer who do not have further testing for PE won’t have a higher frequency of venous thromboembolism during follow-up than patients who undergo routine diagnostic testing.