A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. Anticoagulant vs anti-platelet therapy as prophylactic against cerebral infarction in transient ischemic attacks. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.
Aspirin is only modestly effective in the secondary prevention after cerebral ischemia. Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation (international normalized ratio [INR] 3.0-4.5). Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke (Rankin grade < or =3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event "death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or nonfatal major bleeding complication." The trial was stopped at the first interim analysis. A total of 1,316 patients participated; their mean follow-up was 14 months. There was an excess of the primary outcome event in the anticoagulated group (81 of 651) versus 36 of 665 in the aspirin group (hazard ratio, 2.3; 95% confidence interval [CI], 1.6-3.5). This excess could be attributed to 53 major bleeding complications (27 intracranial; 17 fatal) during anticoagulant therapy versus 6 on aspirin (3 intracranial; 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remains to be determined. This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.
                Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.
                We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.
                Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.
                The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients. No randomized study has yet compared efficacy and safety of aspirin and anticoagulants in patients with spontaneous dissection of the cervical carotid artery (sICAD).
                Prospectively collected data from 298 consecutive patients with sICAD (56% men; mean age 46 +/- 10 years) treated with anticoagulants alone (n = 202) or aspirin alone (n = 96) were retrospectively analyzed. Admission diagnosis was ischemic stroke in 165, TIA in 37, retinal ischemia in 8, and local symptoms and signs (headache, neck pain, Horner syndrome, cranial nerve palsy) in 80 patients, while 8 patients were asymptomatic. Clinical follow-up was obtained after 3 months by neurologic examination (97% of patients) or structured telephone interview. Outcome measures were 1) new cerebral ischemic events, defined as ischemic stroke, TIA, or retinal ischemia, 2) symptomatic intracranial hemorrhage, and 3) major extracranial bleeding.
                During follow-up, ischemic events were rare (ischemic stroke, 0.3%; TIA, 3.4%; retinal ischemia, 1%); their frequency did not significantly differ between patients treated with anticoagulants (5.9%) and those treated with aspirin (2.1%). The same was true for hemorrhagic adverse events (anticoagulants, 2%; aspirin, 1%). New ischemic events were significantly more frequent in patients with ischemic events at onset (6.2%) than in patients with local symptoms or asymptomatic patients (1.1%).
                Within the limitations of a nonrandomized study, our data suggest that frequency of new cerebral and retinal ischemic events in patients with spontaneous dissection of the cervical carotid artery is low and probably independent of the type of antithrombotic treatment (aspirin or anticoagulants). Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine whether oral anticoagulation with medium intensity is more effective than aspirin in preventing future vascular events in patients with transient ischaemic attack or minor stroke of presumed arterial origin.
                In this international, multicentre trial, patients were randomly assigned within 6 months after a transient ischaemic attack or minor stroke of presumed arterial origin either anticoagulants (target INR range 2.0-3.0; n=536) or aspirin (30-325 mg daily; n=532). The primary outcome was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever occurred first. In a post hoc analysis anticoagulants were compared with the combination of aspirin and dipyridamole (200 mg twice daily). Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with ClinicalTrials.gov (NCT00161070).
                The anticoagulants versus aspirin comparison of ESPRIT was prematurely ended because ESPRIT reported previously that the combination of aspirin and dipyridamole was more effective than aspirin alone. Mean follow-up was 4.6 years (SD 2.2). The mean achieved INR was 2.57 (SD 0.86). A primary outcome event occurred in 99 (19%) patients on anticoagulants and in 98 (18%) patients on aspirin (hazard ratio [HR] 1.02, 95% CI 0.77-1.35). The HR for ischaemic events was 0.73 (0.52-1.01) and for major bleeding complications 2.56 (1.48-4.43). The HR for the primary outcome event comparing anticoagulants with the combination treatment of aspirin and dipyridamole was 1.31 (0.98-1.75).
                Oral anticoagulants (target INR range 2.0-3.0) are not more effective than aspirin for secondary prevention after transient ischaemic attack or minor stroke of arterial origin. A possible protective effect against ischaemic events is offset by increased bleeding complications. Oral anticoagulants and aspirin are antithrombotic drugs that are commonly used in patients with vascular disease. We investigated whether either of these treatments prevented more effectively than the other bypass complications after infrainguinal bypass surgery.
                We did a multicentre, randomised, open trial. 2690 patients who had undergone infrainguinal grafting were randomly assigned oral anticoagulants (target international normalised ratio 3.0-4.5, n=1339) or aspirin (80 mg daily, n=1351). We followed up patients for a mean of 21 months. The primary outcome was graft occlusion.
                308 graft occlusions occurred in the oral-anticoagulants group compared with 322 in the aspirin group (hazard ratio 0.95 [95% CI 0.82-1.11]), which suggested no overall advantage for either treatment. Oral anticoagulants were beneficial in patients with vein grafts (0.69 [0.54-0.88]), whereas aspirin had better results for nonvenous grafts (1.26 [1.03-1.55]). The composite outcome of vascular death, myocardial infarction, stroke, or amputation occurred 248 times in the oral-anticoagulants group and 275 times in the aspirin group (0.89 [0.75-1.06]). Patients treated with oral anticoagulants had more major bleeding episodes than those treated with aspirin (108 vs 56; 1.96 [1.42-2.71]).
                Oral anticoagulation was better for the prevention of infrainguinal-vein-graft occlusion and for lowering the rate of ischaemic events. Aspirin was better for the prevention of non-venous graft occlusion, and was associated with fewer bleeding episodes. To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice.
                Randomised controlled trial.
                729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years.
                Primary care in the Netherlands.
                Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2).
                Stroke, systemic embolism, major haemorrhage, and vascular death.
                108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors.
                In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice. The clinical benefit of coronary-artery stenting performed in conjunction with coronary angioplasty is limited by the risk of thrombotic occlusion of the stent as well as hemorrhagic and vascular complications of intensive anticoagulation. We compared antiplatelet therapy with conventional anticoagulant therapy with respect to clinical outcomes 30 days after coronary-artery stenting.
                After successful placement of Palmaz-Schatz coronary-artery stents, 257 patients were randomly assigned to receive antiplatelet therapy (ticlopidine plus aspirin) and 260 to receive anticoagulant therapy (intravenous heparin, phenprocoumon, and aspirin). The primary cardiac end point was a composite measure reflecting death from cardiac causes or the occurrence of myocardial infarction, aortocoronary bypass surgery, or repeat angioplasty. The primary noncardiac end point comprised death from noncardiac causes, cerebrovascular accident, severe hemorrhage, and peripheral vascular events.
                Of the patients assigned to antiplatelet therapy, 1.6 percent reached a primary cardiac end point, as did 6.2 percent of those assigned to anticoagulant therapy (relative risk, 0.25; 95 percent confidence interval, 0.06 to 0.77). With antiplatelet therapy, there was an 82 percent lower risk of myocardial infarction than in the anticoagulant-therapy group, and a 78 percent lower need for repeat interventions. Occlusion of the stented vessel occurred in 0.8 percent of the antiplatelet-therapy group and in 5.4 percent of the anticoagulant-therapy group (relative risk, 0.14; 95 percent confidence interval, 0.02 to 0.62). A primary noncardiac end point was reached by 1.2 percent of the antiplatelet-therapy group and 12.3 percent of the anticoagulant-therapy group (relative risk, 0.09; 95 percent confidence interval, 0.02 to 0.31). Hemorrhagic complications occurred only in the anticoagulant-therapy group (in 6.5 percent). An 87 percent reduction in the risk of peripheral vascular events was observed with antiplatelet therapy.
                As compared with conventional anticoagulant therapy, combined antiplatelet therapy after the placement of coronary-artery stents reduces the incidence of both cardiac events and hemorrhagic and vascular complications. 156 patients with transient ischemic attacks (TIA) or reversible ischemic neurological deficit (RIND) were given prophylactic anticoagulant (AC) treatment against cerebral infarction in a prospective multicenter study from 5 hospitals in southern Sweden. After 2 months of AC treatment, 135 patients remained in the study and were randomized into 2 groups; one continued with AC treatment and one changed to anti-platelet therapy. The patients were followed for 12 months. No significant difference was seen between the 2 groups but 3 completed cerebral infarctions occurred during anti-platelet therapy against one during AC treatment. One cerebral hemorrhage was seen during AC treatment. All completed strokes occurred in men who initially had carotid symptoms. The number of patients with TIA/RIND was somewhat higher in the anti-platelet group whereas myocardial infarctions occurred more often during AC treatment. Compared to the natural history of untreated TIA/RIND both treatments were found to have a prophylactic effect against cerebral infarction. The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users.
                Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy.
                In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina.
Anticoagulants offered no net advantages over antiplatelet agents in acute ischaemic stroke. The combination of low-dose UFH and aspirin appeared in a subgroup analysis to be associated with net benefits compared with aspirin alone, and this merits further research.