Serious Vascular Events In Patients Research Articles

Antiplatelet regimens in the long-term secondary prevention of transient ischaemic attack and ischaemic stroke: an updated network meta-analysis

ObjectiveTo examine the comparative efficacy and safety of different antiplatelet regimens in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack.DesignSystematic review and network meta-analysis.Data sourcesAs on 31 March...

Cilostazol Versus Aspirin for Secondary Prevention of Vascular Events After Stroke of Arterial Origin

For the secondary prevention of stroke of arterial origin, aspirin is the most widely studied and prescribed agent the world over. Cilostazol is both an antiplatelet and vasodilating agent. This agent has been used mainly in Asian populations with noncardioembolic stroke and no clinically evident cardiac disease. ### Objectives The objective of this review was to determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in patients at high vascular risk for subsequent stroke, those with previous transient ischemic attack, or ischemic stroke of arterial origin. ### Search Strategy We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2009, Issue 4), MEDLINE (1950 to May 2010), and EMBASE (1980 to May 2010). In an effort to identify further published, …

Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin.

Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke. To determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in patients at high vascular risk for subsequent stroke, those with previous transient ischaemic attack (TIA) or ischaemic stroke of arterial origin. We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to May 2010) and EMBASE (1980 to May 2010). In an effort to identify further published, ongoing and unpublished studies we searched journals, conference proceedings and ongoing trial registers, scanned reference lists from relevant studies and contacted trialists and Otsuka Pharmaceutical Co Ltd. We selected all randomised controlled trials (RCTs) comparing cilostazol with aspirin where participants were treated for at least one month and followed systematically for development of vascular events. Data extracted from eligible studies included: (1) a composite outcome of vascular events (stroke, myocardial infarction or vascular death) during follow up (primary outcome); (2) separate outcomes of stroke (ischaemic or haemorrhagic, fatal or non-fatal), myocardial infarction (MI) (fatal or non-fatal), vascular death and death from all causes; and (3) main outcomes of safety including any intracranial, extracranial or gastrointestinal (GI) haemorrhage and other outcomes during treatment follow up (secondary outcomes). We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all included studies. We included two RCTs with 3477 Asian participants. Compared with aspirin, cilostazol was associated with a significantly lower risk of composite outcome of vascular events (6.77% versus 9.39%, risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91), and lower risk of haemorrhagic stroke (0.53% versus 2.01%, RR 0.26, 95% CI 0.13 to 0.55). In terms of outcome of safety compared with aspirin, cilostazol was significantly associated with minor adverse effects (8.22% versus 4.95%, RR 1.66, 95% CI 1.51 to 1.83). Cilostazol is more effective than aspirin in the prevention of vascular events secondary to stroke. Cilostazol has more minor adverse effects, although there is evidence of fewer bleeds.

Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients.

Aspirin is the most widely studied and prescribed antiplatelet agent for preventing serious vascular events, reducing the odds of such events among high vascular risk patients by about a quarter. Thienopyridine derivatives inhibit platelet activation by a different mechanism and so may be more effective. To determine the effectiveness and safety of thienopyridine derivatives (ticlopidine and clopidogrel) versus aspirin for preventing serious vascular events (stroke, myocardial infarction (MI) or vascular death) in patients at high risk, and specifically in patients with a previous TIA or ischaemic stroke. We searched the trials registers of the Stroke, Heart and Peripheral Vascular Diseases Cochrane Review Groups (last searched July 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2008), MEDLINE (1966 to August 2008) and EMBASE (1980 to August 2008). We also searched reference lists of relevant papers, and contacted other researchers and the pharmaceutical company Sanofi-BMS (December 2008). All unconfounded, double blind, randomised trials directly comparing a thienopyridine derivative with aspirin in high vascular risk patients. Two review authors independently extracted data and assessed trial quality. We sought additional data from the principal investigators of the largest trials. We included 10 trials involving 26,865 high vascular risk patients. The trials were generally of high quality. Aspirin was compared with ticlopidine in nine trials (7633 patients) and with clopidogrel in one trial (19,185 patients). Compared with aspirin, allocation to a thienopyridine produced a modest, just statistically significant, reduction in the odds of a serious vascular event (11.6% versus 12.5%; odds ratio (OR) 0.92, 95% confidence interval (CI) 0.85 to 0.99), corresponding to the avoidance of 10 (95% CI 0 to 20) serious vascular events per 1000 patients treated for about two years. However, the wide confidence interval includes the possibility of negligible additional benefit. Compared with aspirin, thienopyridines significantly reduced gastrointestinal adverse effects. However, thienopyridines increased the odds of skin rash and diarrhoea, ticlopidine more than clopidogrel. Allocation to ticlopidine, but not clopidogrel, significantly increased the odds of neutropenia. In patients with TIA/ischaemic stroke, the results were similar to those for all patients combined. The thienopyridine derivatives are at least as effective as aspirin in preventing serious vascular events in patients at high risk, and possibly somewhat more so. However, the size of any additional benefit is uncertain and could be negligible. Clopidogrel has a more favourable adverse effects profile than ticlopidine and so is the thienopyridine of choice. It should be used as an alternative to aspirin in patients genuinely intolerant of or allergic to aspirin.

Aspirin Plus Dipyridamole Versus Aspirin for Prevention of Vascular Events After Stroke or TIA

This meta-analysis systematically reviewed randomized controlled trials comparing aspirin plus dipyridamole with aspirin alone in patients with stroke and TIA to determine the efficacy of these agents in preventing recurrent cerebral and systemic vascular events. We performed separate analyses of the incidences of stroke alone and composite outcome of stroke, myocardial infarction, or vascular death. We also performed two subset analyses, planned a priori, to examine effect size based on trials using (1) exclusively immediate-release and (2) predominantly extended-release dipyridamole. The summary results indicate a significant reduction in the overall risk ratio in favor of aspirin plus dipyridamole for stroke alone with relative risk 0.77 (0.67 to 0.89) and the composite end point with relative risk 0.85 (0.76 to 0.94). Studies using immediate-release dipyridamole showed a nonstatistically significant trend in favor of the combination for stroke alone with relative risk 0.83 (0.59 to 1.15) and for the composite outcome with relative risk 0.95 (0.75 to 1.19). Studies using predominantly extended-release dipyridamole showed a statistically significant difference in favor of the combination for stroke alone with relative risk 0.76 (0.65 to 0.89) and for the composite outcome with relative risk 0.82 (0.73 to 0.92). The combination of aspirin plus dipyridamole is more effective than aspirin alone in preventing stroke and other serious vascular events in patients with minor stroke and TIAs. The risk reduction was greater and statistically significant for studies using primarily extended release dipyridamole, which may reflect a true pharmacological effect or lack of statistical power in studies using immediate release dipyridamole.

Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial

Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the effects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs. The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925. After a mean of 4.3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00, p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant (macrovascular 0.92; 0.81-1.04, p=0.16; microvascular 0.91; 0.80-1.04, p=0.16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3.8%] active vs 257 [4.6%] placebo; 0.82, 0.68-0.98, p=0.03) and death from any cause was reduced by 14% (408 [7.3%] active vs 471 [8.5%] placebo; 0.86, 0.75-0.98, p=0.03). There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline. Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confidence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy.

Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials

Angiotensin-converting-enzyme (ACE) inhibitors reduce cardiovascular mortality and morbidity in patients with heart failure or left ventricular systolic dysfunction (LVSD). Three large trials have assessed the effect of ACE inhibitors in stable patients without these conditions but with atherosclerosis. We undertook a systematic review of the Heart Outcomes Prevention Evaluation (HOPE), the European trial on Reduction Of cardiac events with Perindopril among patients with stable coronary Artery disease (EUROPA), and the Prevention of Events with ACE inhibition (PEACE) studies to determine the consistency with which ACE inhibitors reduce total mortality and fatal and non-fatal cardiovascular events. We computed cardiovascular outcomes and total mortality in the 29,805 patients of these three trials, randomly assigned an ACE inhibitor or placebo and followed up for a mean of about 4.5 years. The results were also analysed within the context of five large trials of ACE inhibitors in patients with heart failure or LVSD. When the findings of the HOPE, EUROPA, and PEACE trials were combined, ACE inhibitors significantly reduced all-cause mortality (7.8 vs 8.9%, p=0.0004), cardiovascular mortality (4.3 vs 5.2%, p=0.0002), non-fatal myocardial infarction (5.3 vs 6.4%, p=0.0001), all stroke (2.2 vs 2.8%, p=0.0004), heart failure (2.1 vs 2.7%, p=0.0007), coronary-artery bypass surgery (6.0 vs 6.9%, p=0.0036) but not percutaneous coronary intervention (7.4 vs 7.6%, p=0.481). The composite outcomes of cardiovascular mortality, non-fatal myocardial infarction, or stroke occurred in 1599 (10.7%) of the patients allocated ACE inhibitor and in 1910 (12.8%) of those allocated placebo (odds ratio, 0.82; 95% CIs 0.76-0.88; p<0.0001). Except for stroke and revascularisation, these results were similar to those of the five trials in patients with heart failure or LVSD. ACE inhibitors reduce serious vascular events in patients with atherosclerosis without known evidence of LVSD or heart failure. Results showing these benefits in intermediate-risk patients complement existing evidence of similar benefit in higher-risk patients with LVSD or heart failure. Therefore, use of ACE inhibitors should be considered in all patients with atherosclerosis.

Mortality and Vascular Outcomes in Patients Treated for Thyroid Dysfunction

There are limited studies describing mortality and morbidity in patients treated for hyperthyroidism, and no data exist for people with treated hypothyroidism. The objective of the study was to describe all-cause mortality and vascular mortality and morbidity in patients after treatment for hyperthyroidism and hypothyroidism. This was a population-based cohort study from 1994 to 2001. The study was conducted in Tayside, Scotland. All patients were treated for thyroid dysfunction. Event rates among patients with thyroid dysfunction were compared with rates in the general population. We measured standardized mortality ratio and standardized incidence ratio (SIR). The primary outcome was all-cause mortality. The secondary outcome was serious vascular event, the composite end point of nonfatal myocardial infarction, nonfatal stroke, or vascular death. There were 15,889 primary hypothyroid and 3,888 hyperthyroid patients. There were 3,116,719 patient-years of follow-up in 524,152 subjects in the general population. No increase was found in all-cause mortality or serious vascular events in patients with treated hypothyroidism or hyperthyroidism. Nonfatal ischemic heart disease [SIR 1.23, 95% confidence interval (CI) 1.10-1.36] and dysrhythmias (SIR 1.32, 95% CI 1.11-1.57) were increased in treated hypothyroidism when adjusted for age, sex, diabetic status, and previous vascular disease. In treated stabilized hyperthyroidism, only the risk of dysrhythmias was increased (SIR 2.71, 95% CI 1.63-4.24). Risk of heart failure or cerebrovascular disease was not increased in either patient group. We found no increase in all-cause mortality in subjects with treated thyroid disease. However, there was increased risk of cardiovascular morbidity in patients with treated primary hypothyroidism and dysrhythmias in treated hyperthyroidism.

Triflusal for preventing serious vascular events in people at high risk

Aspirin is the standard treatment for secondary prevention of stroke and other vascular events. Several studies suggest that triflusal may have a better safety profile. To determine in people at high risk of vascular events whether triflusal is an effective and safe treatment for primary and secondary prevention of serious vascular events. We searched the trials registers of the following Cochrane Review Groups: Stroke Group (last searched October 2004), Heart Group, Peripheral Vascular Diseases Group and Metabolic and Endocrine Disorders Group (last searched May 2003). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2003), MEDLINE (1977 to 2003) and EMBASE (1980 to 2003). We searched reference lists and contacted researchers in the field, authors of relevant trials and the drug manufacturer. Randomised and quasi-randomised studies comparing triflusal with placebo or aspirin in people at high risk of vascular events. Two authors independently assessed trial quality and extracted data. The primary outcome was a serious vascular event (non-fatal acute myocardial infarction (AMI), non-fatal ischemic or hemorrhagic stroke, or vascular death). Other efficacy and safety measures collected were frequency of different vascular events, adverse events, minor and major hemorrhages. (1) Aspirin versus triflusal: five studies enrolled patients with stroke or transient ischemic attack (TIA) (4 trials; 2944 patients; followed for 6 to 47 months) or AMI (one trial; 2275 patients; followed for 35 days). Entry criteria were similar within each subgroup of patients. Patient groups were appropriately selected and well matched. The primary outcome in all trials was a composite outcome of vascular events. Trials had no important bias except in one study (217 patients). For the primary outcome of a serious vascular event there was no significant difference between triflusal and aspirin; the odds ratio (OR) was 1.04 (95% confidence interval (CI) 0.87 to 1.23). Significant differences were found for frequency of hemorrhages, both minor (OR 1.60, 95% CI 1.31 to 1.95) and major (OR 2.34, 95% CI 1.58 to 3.46) and for non-hemorrhagic gastrointestinal adverse events (OR 0.84, 95% CI 0.75 to 0.95). Sensitivity analysis of well versus poorly allocated trials showed no significant differences. (2) Triflusal versus placebo: two trials enrolled patients with unstable angina (281 patients) or peripheral arteriopathy (122 patients), who were followed for 6 months. Triflusal was associated with a reduction in serious vascular events (OR 2.29, 95% CI 1.01 to 5.19; OR greater than 1 favours triflusal) and with a higher frequency of adverse events (OR 1.68, 95% CI 1.00 to 2.80). No significant differences were found between triflusal and aspirin for secondary prevention of serious vascular events in patients with stroke or TIA and AMI. However, our review cannot exclude moderate differences in efficacy. Triflusal was associated with a lower risk of hemorrhagic complications.

Adding aspirin to clopidogrel after TIA and ischemic stroke

Antiplatelet therapy is effective for reducing the risk of recurrent stroke and other serious vascular events in patients with recent TIA and ischemic stroke. Effective antiplatelet agents include aspirin, ticlopidine, clopidogrel, dipyridamole, and the combination of aspirin and dipyridamole. The combination of aspirin and clopidogrel is more effective than aspirin in patients with acute coronary syndrome but is more hazardous than clopidogrel alone in patients with recent TIA and ischemic stroke. Further trials are needed to determine whether the combination of aspirin and clopidogrel may have a role immediately after TIA and ischemic stroke in patients with symptomatic large artery atherothromboembolism and continued for approximately 3 months before switching to less hazardous antiplatelet regimens.

Antiplatelet drugs.

Antiplatelet drugs protect against myocardial infarction, stroke, cardiovascular death and other serious vascular events in patients with a history of previous vascular events or known risk factors for cardiovascular disease. Aspirin reduces the risk of serious vascular events in patients at high risk of such an event by about a quarter and is recommended as the first-line antiplatelet drug. Clopidogrel reduces the risk of serious vascular events among high-risk patients by about 10% compared with aspirin. It is as safe as aspirin, but much more expensive. It is an appropriate alternative to aspirin for long-term secondary prevention in patients who cannot tolerate aspirin, have experienced a recurrent vascular event while taking aspirin, or are at very high risk of a vascular event (>/= 20% per year). Addition of clopidogrel to aspirin reduces the risk of serious vascular events among patients with non-ST-segment elevation acute coronary syndromes by 20%, and patients undergoing percutaneous coronary intervention by 30%, compared with aspirin alone. Addition of a glycoprotein IIb/IIIa receptor antagonist to aspirin reduces the risk of vascular events among patients with non-ST-segment elevation acute coronary syndromes by 10% and among patients undergoing percutaneous coronary intervention by 30%, compared with aspirin alone; it appears to provide incremental benefit in patients also treated with clopidogrel. Addition of dipyridamole to aspirin seems to be more effective than aspirin alone for preventing recurrent stroke, but its overall effect in preventing serious vascular events in patients with ischaemic stroke and transient ischaemic attack has not been determined.

Homocysteine levels in patients with stroke: clinical relevance and therapeutic implications.

High plasma levels of the amino acid homocysteine have been implicated in the development of vascular diseases, including stroke. Elevated plasma levels of total homocysteine (tHcy) above 15 micromol/L are present in less than 5% of the general population, but in as many as 50% of patients with stroke (and other atherothromboembolic vascular diseases). However, it remains uncertain whether a high tHcy level is a causal risk factor for stroke and should be lowered, or is a marker of another factor associated with stroke (e.g. acute tissue damage or tissue repair after an acute vascular event) and therefore should not be lowered. Plasma levels of tHcy can be lowered effectively by folic acid, vitamin B(6) and vitamin B(12) supplementation, and controlled trials have shown some beneficial effects on surrogate markers of vascular function. However, these markers are not established vascular risk factors or valid predictors of 'hard' clinical vascular outcome events. Until it has been shown in large randomised trials [such as the ongoing Vitamins to Prevent Stroke Study (VITATOPS) and the Vitamins in Stroke Prevention (VISP) study] that multivitamin therapy reduces the rate of recurrent stroke and other serious vascular events in patients with prior stroke or transient ischaemic attack, widespread screening for, and treatment of, high tHcy levels remains experimental and cannot be recommended.

Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials.

Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately 2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by approximately 2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.

Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients.

The most widely studied and prescribed antiplatelet agent for the prevention of stroke and other serious vascular events among high vascular risk patients is aspirin. Aspirin inhibits platelet activation by inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of a serious vascular event by about a quarter. The thienopyridines (ticlopidine and clopidogrel) inhibit platelet activation by a different mechanism to aspirin (blocking the ADP receptor on platelets), and so may be more effective than aspirin. The objective of this review was to determine the effectiveness and safety of thienopyridine derivatives (ticlopidine and clopidogrel) versus aspirin for the prevention of serious vascular events (stroke, myocardial infarction (MI) or vascular death) in patients at high risk of such events, and specifically in patients with a previous TIA or ischaemic stroke. We searched the Cochrane Stroke Group trials register (most recent search: March 1999) and the Antithrombotic Trialists' database, and also contacted Sanofi pharmaceutical company. All unconfounded, double blind, randomised trials directly comparing ticlopidine or clopidogrel with aspirin in high vascular risk patients. Two reviewers independently extracted data and assessed trial quality. Additional data were sought from the principal investigators of the largest trial. Four trials involving a total of 22,656 high vascular risk patients were included. The trials were of high quality and comparable. Aspirin was compared with ticlopidine in three trials (3471 patients) and with clopidogrel in one trial (19,185 patients). Allocation to a thienopyridine was associated with a modest, yet statistically significant, reduction in the odds of a serious vascular event (12. 0% vs 13.0%; OR: 0.91, 95% CI: 0.84 to 0.98; 2p = 0.01), corresponding to the avoidance of 11 (95% CI: 2 to 19) serious vascular events per 1000 patients treated for about two years. There was also a reduction in stroke (5.7% vs 6.4%; OR: 0.88, 95% CI: 0.79 to 0.98; 7 [95% CI: 1 to 13] strokes avoided per 1000 patients treated for two years). Compared with aspirin, thienopyridines produced a significant reduction in the odds of gastrointestinal haemorrhage and other upper gastrointestinal upset, but a significant increase in the odds of skin rash and of diarrhoea. However, the increased odds of skin rash and diarrhoea were greater for ticlopidine than for clopidogrel. Allocation to ticlopidine, but not clopidogrel, was associated with a significant increase in the odds of neutropenia (2.3% vs 0.8%; OR: 2.7, 95% CI: 1.5 to 4.8). In the subset of patients with TIA/ischaemic stroke, the results were similar to those for all patients combined. However, since these patients are at particularly high risk of stroke, allocation to a thienopyridine was associated with a larger absolute reduction in stroke (10.4% vs 12.0%; OR: 0.86, 95% CI: 0.75 to 0.97; 16 [95% CI: 3 to 28] strokes avoided per 1000 patients treated for two years). The available randomised evidence shows that the thienopyridine derivatives are modestly but significantly more effective than aspirin in preventing serious vascular events in patients at high risk (and specifically in TIA/ischaemic stroke patients), but there is uncertainty about the size of the additional benefit. The thienopyridines are also associated with less gastrointestinal haemorrhage and other upper gastrointestinal upset than aspirin, but an excess of skin rash and diarrhoea. The risk of skin rash and diarrhoea is greater with ticlopidine than with clopidogrel. Ticlopidine, but not clopidogrel, is associated with an excess of neutropenia and of thrombotic thrombocytopenic purpura.

Antiplatelet Therapy for Preventing Stroke in Patients With Nonvalvular Atrial Fibrillation and No Previous History of Stroke or Transient Ischemic Attacks

Antiplatelet agents such as aspirin are modestly efficacious for preventing serious vascular events in patients with atrial fibrillation (AF) who are not treated with more efficacious oral anticoagulants. Nonvalvular AF carries an increased risk of stroke. Antiplatelet therapy (APT) is proven effective for stroke prevention in most patients at high-risk for vascular events, but its value for primary stroke prevention in patients with nonvalvular AF merits separate consideration because of the suspected cardioembolic mechanism of most strokes in AF patients. The goal of this review is to assess the efficacy and safety of long-term APT for primary prevention of stroke in patients with chronic nonvalvular AF. We searched the Cochrane Stroke Group Trials Register (August 2004). In addition, …