Combination Of Low-dose Aspirin Research Articles

Current Oral Antiplatelet Agents to Prevent Atherothrombosis

Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2–19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59–0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0–20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.

Update on antiplatelet therapy for stroke prevention.

The high rates of mortality and long-term disability associated with ischemic stroke, coupled with its prevalence, necessitate good, long-term preventive strategies. Risk-factor management is effective for individuals with preclinical and clinical cerebrovascular disease. Patients suffering from a transient ischemic attack or stroke are particularly vulnerable to subsequent stroke. Most of these individuals are candidates for antiplatelet treatment to prevent a recurrence. Available antiplatelet therapies include aspirin, ticlopidine, and clopidogrel. The combination of low-dose aspirin plus extended-release dipyridamole has been shown to offer safe, effective antiplatelet therapy for appropriate patients. In the second European Stroke Prevention Study, the combination was found to be significantly more effective than either drug alone, at the cost of relatively few treatment-related adverse effects. This combination is currently recommended as one of the first-line treatments for stroke prevention after first transient ischemic attack or stroke.

Update

Antiphospholipid antibodies (aPL) represent a spectrum of (apparent) phospholipid-binding antibodies. aPL include the false-positive serologic test for syphilis, the lupus anticoagulant, and the anticardiolipin antibody. A distinct clinical syndrome has been associated with these antibodies, the "antiphospholipid antibody syndrome," which is characterized by the triad of recurrent venous and arterial thrombosis, thrombocytopenia, and recur-rent fetal loss, as well as a number of other organ system manifestations. In addition to the recognition of newer clinical manifestations of this syndrome, understanding of the basic immunology and pathophysiology has changed dramatically during the last several years: antiphospholipid anti-bodies are now known to recognize two or more phospholipid-binding proteins rather than pure phospholipid, potentially explaining the diversity in clinical presentations and complications. Current therapies are based on long-term anticoagulation for prevention of recurrent thromboses and a combination of low dose aspirin with heparin during pregnancy. The discovery of beta2-glycoprotein I and other phospholipid-binding proteins as antibody epitope sites may lead to novel therapies in the near future.

Effect of low-dose aspirin in combination with stable fish oil on eicosanoids: Karin Engström, Tom Saldeen and Rolf Wallin. Department of Forensic Medicine, University of Uppsala, Uppsala, Sweden

Effect of low-dose aspirin in combination with stable fish oil on eicosanoids: Karin Engström, Tom Saldeen and Rolf Wallin. Department of Forensic Medicine, University of Uppsala, Uppsala, Sweden

Safety and anticoagulation effect of a low-dose combination of warfarin and aspirin in clinically stable coronary artery disease

The hypothesis that the combination of low-dose aspirin and warfarin therapy is more effective than aspirin alone in secondary prophylaxis after myocardial infarction is to be examined in the Coumadin Aspirin Reinfarction Study. This pilot study addressed the safety and anticoagulation effect of a fixed, low-dose combination in 114 patients (aged 64 ± 8 years, 85% men) with stable coronary artery disease receiving 3 mg of warfarin plus 80 mg of aspirin daily for 8 weeks. The international normalized ratio (INR) was measured within 72 hours of initial therapy, and weekly. Of the 110 patients with evaluable INRs, 87 patients (79%) maintained the 3 + 80 mg combination, 19 (17%) had the dose reduced to 1 mg warfarin + 80 mg aspirin, and 4 (4%) discontinued therapy because of a confirmed INR of ≥4.5. At steady state, patients had INRs of 1.48 ± 0.41 (3 + 80 mg group) and 1.21 ± 0.23 (1 + 80 mg group), and inter- and intra-patient variability (estimated by the mean of the between- and within-patient SDs at steady state) was 0.49 ± 0.08 and 0.13 ± 0.14, respectively. There was no apparent effect of age on INR distribution. Microscopic hematuria was the most frequent (20%) adverse clinical event, but was unrelated to the INR. Three patients required discontinuation of therapy because of bleeding events (persistent hematuria and epistaxis). A fixed low-dose combination of warfarin and aspirin results in a predictable and stable increase in the INR in a large proportion of patients with coronary artery disease. Provided that early INR testing is undertaken in order to identify patients with significant sensitivity to low-dose warfarin and to establish steady-state dosing, the Coumadin Aspirin Reinfarction Pilot Study suggests that this treatment modality may be safe for long-term administration as secondary prophylaxis.

Combined aspirin and sulfinpyrazone in the prevention of recurrent hemodialysis vascular access thrombosis

We carried out a pilot study in 15 hemodialysis patients with recurrent vascular access thrombosis to examine whether the combination of low dose aspirin (85 mg once daily) and sulfinpyrazone (200 mg three times daily) is safe and effective in the prevention of vascular access thrombosis. Hemostatic measurements were performed prior to and after four weeks of starting the drug combination. Baseline values for fibrinopeptide A were elevated in all patients while those for platelet factor 4, fibrinogen, antithrombin III and protein C were generally within normal limits. A major reduction in the frequency of vascular access thrombosis from 0.114 per month to 0.04 per month was noted during combined drug treatment (p < 0.001). Although in vitro platelet aggregation to various stimuli was markedly suppressed and platelet thromboxane B 2 formation was almost completely inhibited in patients on aspirin/sulfinpyrazone, this was not associated with a significant further prolongation of the bleeding time. A relatively high rate of complications, particularly mild gastrointestinal bleeding, was noted in patients on aspirin/sulfinpyrazone that could not be predicted on the basis of pre-treatment hemostatic test results.

Low-dose aspirin versus anticoagulants for prevention of coronary graft occlusion

The prevention of graft occlusion by aspirin (100 mg/day) or heparin followed by phenprocoumon was investigated in a randomized trial in 235 patients after aortocoronary bypass operation. Aspirin treatment started 24 hours before, and heparin 6 hours and phenprocoumon 2 days after surgery. The results of the vein graft angiography and the clinical outcome 3 months postoperatively did not differ: 22% of 218 vein graft distal anastomoses in the aspirin group and 20% of 272 in the anticoagulant group were occluded. At least 1 occluded distal anastomosis was present in 38% of 74 patients in the aspirin-treated group and in 39% of 86 in the anticoagulant group. Worst-case analysis of all randomized patients snowed graft occlusions, cardiovascular complications or lost to follow-up in 42% of 122 aspirin-treated patients compared with 41% of 113 patients treated with anticoagulants. For grafts with endarterectomy the occlusion rate was lower in the aspirin (12% of 49) than in the anticoagulant (22% of 41) group (p ≤ 0.05). Increased perioperative Mood loss in the aspirin group (1,211 ± 814 ml in the first 48 hours vs 874 ± 818 ml in the anticoagulant group [p ≤ 0.001]) without a higher reoperation rate indicates effective platelet inhibition with low-dose aspirin. Because occlusion rates were equal but high in these patients with advanced stage of coronary artery disease, a combination of low-dose aspirin and anticoagulation should be investigated to reduce graft occlusion rates further.