Safety Of Aspirin Research Articles

Effects of Changing Guidelines on Prescribing Aspirin for Primary Prevention of Cardiovascular Events

The use of low-dose aspirin for primary prevention of cardiovascular events in patients at elevated risk for cardiovascular disease (CVD) is increasingly being questioned. Aspirin may not benefit this population and may increase the risk of major bleeding events. Data support aspirin use in patients with known CVD. This is a secondary analysis of de-identified electronic health record (EHR) data from 131,050 individuals with known CVD or elevated risk for CVD as determined by diagnostic, demographic, and clinical data collected from 33 primary care practices in 11 different clinical organizations across 6 states. The percentage of the population of each cohort with aspirin recorded on their medication list, created through risk base analysis, was observed across 4 time periods. From 2007 to 2011, aspirin usage reflected in the EHR increased for the entire population and for each individual high-risk diagnosis. The percentage of the population initiating aspirin therapy for primary prevention within a year of diagnosis of CVD risk factors or CVD "equivalency" increased between 2007 and 2011. Among those with a new diagnosis of CVD, aspirin usage also steadily increased over the 4-year period, indicating no negative impact from new negative primary prevention studies. Primary care clinicians have a central role in providing evidence-based preventive services and should integrate revised information into their practice to improve outcomes. Even with new evidence against the use of aspirin for primary prevention, it is difficult to change beliefs about the effectiveness and safety of aspirin, as reflected in the behavior of physicians and patients.

Are MPNs Vascular Diseases?

A high risk of arterial and venous thrombosis is the hallmark of chronic myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Clinical aspects, pathogenesis and management of thrombosis in MPN resemble those of other paradigmatic vascular diseases. The occurrence of venous thrombosis in atypical sites, such as the splanchnic district, and the involvement of plasmatic prothrombotic factors, including an acquired resistance to activated protein C, both link MPN to inherited thrombophilia. Anticoagulants are the drugs of choice for these complications. The pathogenic role of leukocytes and inflammation, and the high mortality rate from arterial occlusions are common features of MPN and atherosclerosis. The efficacy and safety of aspirin in reducing deaths and major thrombosis in PV have been demonstrated in a randomized clinical trial. Finally, the Virchow's triad of impaired blood cells, endothelium and blood flow is shared both by MPN and thrombosis in solid cancer. Phlebotomy and myelosuppressive agents are the current therapeutic options for correcting these abnormalities and reducing thrombosis in this special vascular disease represented by MPN.

Efficacy and safety of aspirin, clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02-59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan-Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.

The efficacy and safety of aspirin plus dipyridamole versus aspirin in secondary prevention following TIA or stroke: A meta-analysis of randomized controlled trials

ObjectiveStroke is becoming a common disease worldwide, and has an increased rate of recurrence yearly after a transient ischemic attack (TIA) or stroke. Aspirin, dipyridamole, clopidogrel and aspirin plus dipyridamole combination therapy have been recommended for the secondary prevention of stroke in Americans. DesignWe performed meta-analyses to assess the effectiveness and safety of combination therapy with aspirin and dipyridamole (A+D) versus aspirin (A) alone in secondary prevention after transient ischemic attack (TIA) or stroke of presumed arterial origin within one week and six months. Data sourcesMedline, Embase, and the Cochrane Library. Selection of studiesEligible studies were completed randomized controlled trials investigating the effect of aspirin plus dipyridamole versus aspirin in patients with previous TIA or stroke. ResultsFive trials involving the use of aspirin and dipyridamole were included, 4318 allocated to A+D and 4304 to A alone. Meta-analysis of trials showed a significant protective effect of reducing or preventing recurrence of stroke (P=0.01), and ischemic event (P=0.003). The statistics showed no significant difference in vascular event, death from all cause and myocardial infarction (P>0.05). There were similarities with all bleeding events, major bleeding and intracranial hemorrhage was significant (P>0.05) between two groups. ConclusionsAspirin plus dipyridamole combination therapy was beneficial in reducing the recurrence of stroke, and did not increase the bleeding event. Hence, aspirin plus dipyridamole combination therapy is effective and safe for the secondary prevention of stroke.

Maintenance Treatment of Childhood Primary Angiitis of Central Nervous System with Aspirin and Azathioprine

Objectives: We aimed to assess the efficacy and safety of Aspirin and Azathioprine in prevention of recurrence of childhood primary angiitis of central nervous system (cPACNS) after induction therapy with intravenous pulse Methylprednisolone/ Immunoglobulin, and describe long-term neurological outcomes in a cohort of children with this disorder. Study type: Case series Methods: The cohort comprised of consecutive patients diagnosed as having childhood primary angiitis of central nervous system (cPACNS), based on clinical and vascular imaging findings, including identification of arterial stenosis on conventional angiography or Magnetic Resonance (MR) angiography. Over the period of 2 years, 68 children with cPACNS were admitted, who presented within 14 days of onset of the symptoms. Patients with ischemic infarcts were initially treated in conjunction with Heparin/ Oral Anticoagulant and IV Methylprednisolone and/or Immunoglobulin, and this was followed by long term use of Aspirin and Azathioprine. Patient were followed in the out patients clinics and were systemically assessed for clinical presentation, hospital course, adverse effects of anticoagulants, aspirin and Azathioprine. The primary outcomes were 1) morbidity and mortality, 2) Paediatric Stroke Outcome Measure (PSOM) scores after the median follow-up of 34 months. Statistical analysis: Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 12.0 (Chicago, IL). Frequencies were calculated for categorical data including gender, final outcome and complications of anticoagulation therapy. Mean with 95% SD was calculated for nominal variables including age. Fisher’s exact test or chi squared test were used, where appropriate to determine any significant difference in outcome with different presenting features, taking p<0.05 as significant. Results: From January 2008, to December 2010, 94 patients with cPACNS were enrolled, 68 of whom met the inclusion criteria and were given induction therapy. The median age at diagnosis was 8.5 years (range 1•6-16 years). 56 patients (boys 35/56, 62%, girls 21/56, 38%) completed induction therapy (with acute mortality of 12/68, 18.5%) and received maintenance therapy with aspirin (n=40) or aspirin and azathioprine (n=16). At the median follow-up of 34 months, of the total 56 patients is; total 30 (30/56, 53.5%) had relapse/flare: first relapse within 24 months after discharge 35.7%: 20 (20/56, 35.7%) died, 15 (15/56, 26.7%) in association with relapse of cPACNS, 5 (5/56, 9%) died due to other causes:14 (14/56, 25%) were receiving Aspirin only: 11 (11/56, 19.6%) were off any medication : 7 (7/56, 12.3%) were receiving both Azathioprine and Aspirin and 4 (4/56, 7.2%) were lost in follow-up. The Neurological findings among 32 patients available to be assessed at last follow up by Paediatric Stroke Outcome Measurement (PSOM) were; normal 8 (8/32, 25%); minor disabilities 10 (10/32, 31.25%; moderate disabilities 10 (10/32, 31.25%) and severe disabilities 4 (4/32, 12.5%). No serious side effects were documented due to low dose aspirin and azathioprine therapy. Conclusion: The spectrum of cPACNS in children includes both progressive and non-progressive forms. Recurrence of cPACNS was high within six months after discharge with high mortality, more among the patients treated with Aspirin than with Azathioprine in conjunction with Aspirin, after initial treatment with IV Methylprednisolone / Immunoglobulin and heparin/ oral anticoagulants.

Aspirin for the Prophylaxis of Venous Thromboembolic Events in Orthopedic Surgery Patients: A Comparison of the AAOS and ACCP Guidelines with Review of the Evidence

The American Academy of Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP) have both developed evidence-based guidelines to prevent venous thromboembolism (VTE) in high-risk orthopedic surgery patients. Recent changes to these documents have brought them into agreement as to the inclusion of aspirin as an appropriate option for VTE prophylaxis in this patient population. To evaluate the appropriateness of aspirin to prevent VTE in high-risk orthopedic surgery patients. Guidelines published by the AAOS in 2011 and the ACCP in 2012 were compared regarding their recommendations on the use of aspirin for the prevention of VTE. A literature search was also conducted to identify clinical trials that evaluated the use of aspirin for the prevention of VTE in this patient population. Search terms included the MeSH terms venous thromboembolism; venous thrombosis; pulmonary embolism; aspirin; arthroplasty, replacement, knee; arthroplasty, replacement, hip; and hip fractures/surgery. Any study that evaluated aspirin, even in combination with another method of prophylaxis (such as pneumatic compression devices), and had been published during or after 1985 was included. Randomized controlled trials, meta-analyses, and other large pooled and retrospective reviews have failed to consistently arrive at similar conclusions regarding the efficacy and safety of aspirin as an option for VTE prophylaxis in patients undergoing total knee arthroplasty (TKA), total hip arthroplasty (THA), or hip fracture surgery (HFS). Disagreements in the appropriateness of surrogate markers for safety and efficacy have resulted in differing recommendations from the ACCP and AAOS. The primary argument lies in the appropriateness of deep vein thrombosis as a surrogate marker for more serious outcomes such as pulmonary emboli. Recent changes to both the ACCP and AAOS guidelines are in agreement for those who choose to use aspirin for chemoprophylaxis of VTE. Current surgical care improvement project measures do not include aspirin as an appropriate sole option for the prevention of VTE, but in patients undergoing elective TKA or who have a contraindication to pharmacologic prophylaxis and undergo a THA or HFS, aspirin in conjunction with compression devices as part of a multimodal approach would meet these measures. Data do not support the hypothesis that aspirin is less likely to cause adverse bleeding events than more potent anticoagulants.

Influence of Aspirin on Pilocarpine-Induced Epilepsy in Mice

Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.

Clopidogrel

Dual antiplatelet therapy with acetylsalicylic acid (aspirin) and clopidogrel is a guideline-recommended standard of care for patients with acute coronary syndromes (ACS) and those who undergo percutaneous coronary intervention (PCI). Despite a large body of clinical evidence obtained from randomized clinical trials and patient registries supporting the efficacy and safety of aspirin plus clopidogrel therapy in these patients, questions concerning the optimal use of dual antiplatelet therapy remain. Widely debated topics pertaining to dual antiplatelet therapy in patients with ACS or undergoing PCI include (i) the appropriate clopidogrel loading dose; (ii) the optimal time to initiate the clopidogrel loading dose; (iii) the optimal duration of dual antiplatelet therapy following ACS or PCI; (iv) impact of variability of platelet response on patient outcomes; and (v) the role of other recommended and emerging P2Y₁₂ antagonists. This review discusses these ongoing controversies regarding the optimal use of dual antiplatelet therapy with aspirin and clopidogrel in patients with ACS or those undergoing PCI.

Venous thromboembolism prophylaxis: do trial results enable clinicians and patients to evaluate whether the benefits justify the risk? proceedings of an ad hoc working group meeting

Venous thromboembolism prophylaxis: do trial results enable clinicians and patients to evaluate whether the benefits justify the risk? proceedings of an ad hoc working group meeting

Thalidomide thromboprophylaxis in multiple myeloma: A review of current evidence

Currently multiple antithrombotic agents are used for thalidomide thromboprophylaxis in multiple myeloma patients. Agents used include low-dose aspirin, fixed low-dose and therapeutic warfarin and prophylactic low molecular weight heparin. To evaluate the evidence for the efficacy and safety of aspirin, warfarin and low molecular weight heparin thromboprophylaxis in multiple myeloma patients on thalidomide a literature search was conducted in May and June 2011. Databases searched included the Cochrane Database of Systemic Reviews and the Database of Abstracts of Reviews of Effects, Evidence Based Medicine Reviews and Ovid MEDLINE. The search was restricted to English language articles and limited to articles published from 2005 to 2011. Most studies consisted of small prospective cohort studies not originally designed to assess thromboprophylaxis as an outcome. A single comparative randomized trial, several retrospective review articles, two meta-analyses and two clinical practice guidelines were also identified. Current evidence fails to demonstrate a clear advantage of any particular thromboprophylaxis strategy. Results from the only prospective comparative randomized trial found no significant differences among aspirin, warfarin and low molecular weight heparin. More studies are required that consider not only efficacy and safety, but also costs, lifestyle burden and patient preference.

Mechanisms of aggregation inhibition by aspirin and nitrate-aspirin prodrugs in human platelets

Aspirin is the mainstay of anti-platelet therapy in the secondary prevention of cardiovascular disease. However, problems with aspirin safety and resistance demand clinical strategies based on multiple pharmacological approaches. Prodrugs of aspirin may offer beneficial effects in terms of gastro-intestinal safety and multiple pharmacological approaches. However, the pharmacological profile of aspirin prodrugs in human platelets has not been completed yet. We aimed to compare the effects of aspirin and prodrugs of aspirin (1-5) on human platelet aggregation stimulated by ADP and collagen and associated receptor expression (GPIIb/IIIa and P-selectin) in platelet-rich plasma (PRP) and washed platelets (WP). As aspirin is released from prodrugs following esterase hydrolysis we studied the expression and activity of butyrylcholineterase (BuChE) and carboxyesterase (CE) in plasma and platelets. The mechanism of prodrug-induced platelet aggregation inhibition was explored by studying the effects of plasma and purified human BuChE on aggregation. Finally, the relative contribution of nitric oxide (NO) bioactivity to nitrate-containing prodrugs of aspirin-induced inhibition of aggregation was determined using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,) a selective inhibitor of the soluble guanylyl cyclase. ST0702, 2, a nicotinic acid-aspirin codrug was equipotent with aspirin with respect to inhibition of collagen-induced platelet aggregation. Compound 4, a NO releasing aspirin was the most potent inhibitor of ADP-induced platelet aggregation, an effect partially reversed by ODQ. The platelet inhibitory effects of aspirin prodrugs were time-dependent as the maximal inhibitory effects against collagen-induced aggregation were achieved by aspirin at 2 min, 1 at 5 min and ST0702 at 15 min. The aspirin prodrugs were significantly less potent in WP than in PRP and the reverse was true of aspirin. In the presence of complete BuChE inhibition in PRP, there was almost complete loss of aspirin prodrug, but not aspirin anti-aggregatory activity. Interestingly, CE activity was observed in WP and platelet lysate with pNPA substrate. Accordingly, 1 and ST0702 retained 50% and 100% anti-aggregatory activity at maximal concentrations in WP, which was attenuated in the presence of esterase inhibitor phenylmethylsulphonyl fluoride. The inhibitory effect of aspirin prodrugs in PRP is due to prodrug activation by BuChE. In contrast, the platelet-inhibitory effects of aspirin prodrugs in WP may be mediated through the activity of platelet CE. Compound 4, a NO-containing aspirin prodrug, may exert dual inhibitory effects in platelets. Thus, aspirin prodrugs effectively inhibit human platelet aggregation and as such may be an alternative to conventional aspirin.

Role of aspirin in tuberculous meningitis: A randomized open label placebo controlled trial

ObjectiveTo evaluate the efficacy and safety of aspirin in preventing stroke and mortality in tuberculous meningitis (TBM). MethodsPatients with TBM diagnosed on the basis of clinical, MRI and cerebrospinal fluid (CSF) criteria were randomized into aspirin 150mg daily or placebo. All the patients received four drug antitubercular treatment- RHZE (rifampicin, isoniazide, pyrazinamide and ethambutol) with or without corticosteroid. The primary endpoint was MRI proven stroke at 3months and secondary end points were mortality and functional outcome assessed by Barthel Index score at 3months. The adverse drug reactions were also analyzed. Results118 TBM patients were randomized into aspirin and placebo groups. The baseline demographic, clinical (severity of meningitis, MRI and CSF changes) were not significantly different between the two groups. 19 (16.1%) patients lost from follow up. 21 (33.3%) patients developed stroke after randomization which was insignificantly lesser in aspirin (24.2%) compared to the placebo group (43.3%; OR 0.42, 95%CI 0.12-1.39). Aspirin resulted in absolute risk reduction of stroke in 19.1% and significant reduction in mortality compared to placebo (21.7% Vs 43.4%, P=0.02). On binary logistic regression analysis, the age (OR 1.09, CI 1.03-1.14, P=0.001) was the only independent risk factor of stroke and aspirin was significantly related to survival (OR 3.17, 95% CI 1.21-8.31). Aspirin was well tolerated and was not withdrawn in any patient because of side effects. InterpretationAspirin resulted in insignificantly lesser strokes and significantly reduced 3month mortality in patients with TBM.

Parnaparin versus aspirin in the treatment of retinal vein occlusion. A randomized, double blind, controlled study

Introduction Retinal vein occlusion (RVO) is a common cause of unilateral visual loss. Evidence based treatment recommendations for patients with RVO cannot be made because of the lack of adequate clinical trials. To compare the efficacy and safety of aspirin and of a low molecular weight heparin, parnaparin, in the treatment of RVO. Materials and Methods In a multicenter, randomized, double blind, controlled trial eligible patients with a delay between symptoms onset and objective diagnosis of less than 15 days were randomized to aspirin 100 mg/day for 3 months or to a fixed daily dose of parnaparin, 12.800 IU for 7 days followed by 6.400 IU for a total of 3 months. Primary end-point of the study was the incidence of functional worsening of the eye with RVO at 6 months, as assessed by fluorescein angiography, visual acuity, and visual field. Study end-points were adjudicated by an independent committee. Results Sixty-seven patients were enrolled in the study and 58 of them (28 treated with parnaparin, 30 with aspirin) were evaluable for the analysis. Baseline characteristics were well balanced between groups. Functional worsening was adjudicated in 20.7% of patients treated with parnaparin and in 59.4% of patients treated with ASA (p = 0.002). Recurrent RVO was diagnosed in 3 patients, all treated with ASA (p = n.s.). Bleeding rates were similar between the two groups. Conclusions Parnaparin appears to be more effective than aspirin in preventing functional worsening in patients with RVO. The results of this study need to be confirmed in a larger clinical trial. Trial registration number: Clinical trials.gov NCT00732927.

Aspirin vs anticoagulation in carotid artery dissection

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).

Aspirin and Extended-Release Dipyridamole vs. Clopidogrel for Recurrent Stroke

Conclusion: Rates of recurrent stroke are similar in patients with stroke treated with aspirin and extended release dipyridamole vs those treated with clopidogrel. Summary: Surviving patients with ischemic stroke are at risk for recurrent stroke. Multiple trials have proven the efficacy of antiplatelet agents in prevention of recurrent stroke after non-cardioembolic stroke. Which particular antiplatelet therapy may work best in the prevention of recurrent stroke is unknown. This trial studied the relative efficacy and safety of aspirin plus extended-release dipyridamole (ERDP) for prevention of recurrent stroke compared with patients treated with clopidogrel. This is a double-blind, two-by-two factorial trial. Patients were randomly assigned to receive 75 mg of aspirin plus 200 mg of ERDP twice daily, or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary end point was a composite of myocardial infarction, stroke, or death from cardiovascular cause. The trial was designed as a noninferiority trial with sequential statistic testing of noninferiority, followed by superiority testing. A total of 20,332 patients were followed up worldwide, with a mean follow-up of 2.5 years. In patients receiving aspirin and ERDP, recurrent stroke occurred in 916 (9%). In patients receiving clopidogrel, recurrent stroke occurred in 898 (8.8%), with a hazard ratio (HR) of 1.01 (95% confidence interval [CI], 0.92-1.11). The secondary composite outcome occurred in 13.1% of patients in each group (HR for aspirin/ERDP, 0.99; 95% CI, 0.92-1.07). Patients treated with aspirin/ERDP had 4.1% (n = 419) major hemorrhagic events compared with 3.6% (n = 365) in patients treated with clopidogrel (HR, 1.15; 95% CI, 1.00-1.32) and had more intracranial hemorrhage (HR, 1.42; 95% CI, 1.11-1.83). The net risk of a major hemorrhagic event or recurrent stroke was similar in the two groups, 11.7% in the aspirin/ERDP group vs 11.4% in the clopidogrel group (HR, 1.03; 95% CI, 1.95-1.11). Comments: The study indicates no significant difference between the use of aspirin/ERDP vs clopidogrel in preventing recurrent stroke. This was a huge study with high patient numbers and international representation from 35 countries or regions. The results of the study, therefore, should be generalizable worldwide. Although the study failed to identify a superior treatment to prevent recurrent stroke, we now know the expected risk of recurrent stroke in patients treated according to the study protocol. The study has also provided us safety and efficacy data for physicians concerning individual treatment decisions for their patients with ischemic stroke.

Efficacy and safety of aspirin in prevention of venous thromboembolism after total joint arthroplasty

To study the efficacy and safety of aspirin in prophylaxis of venous thromboembolism (VTE) after total joint arthroplasty. 240 patients who received total joint arthroplasty, 157 undergoing total knee arthroplasty (TKA) and 83 undergoing total hip arthroplasty (THR), were divided into 2 basically matched groups, Group A (n = 100), receiving aspirin enteric-coated tablets 100 mg/day since the first day after operation till discharge 10-14 days after operation, and Group B (n = 140), receiving subcutaneous injection of low molecular weight heparin (LMWH) once daily for 10 d. The effects and safety were evaluated. 13 patients (13.0%) were diagnosed with deep venous thrombosis (DVT) in Group A, 7 of them were symptomatic, 3 were suspected of pulmonary embolism, and 2 suffered from cardio-cerebrovascular event. In Group B, 10 patients (7.1%) had DVT, 4 of them were symptomatic; suspicious pulmonary embolism and cardio-cerebrovascular event were diagnosed in 3 and 8 patients respectively. There were no statistic significances between the two groups in all these aspects. The quantity of bleeding, decrease of hemoglobin, hematoma rate, and infection rate of Group A were (693.4 +/- 480.1) ml, (32.9 +/- 18.0) g/L, 1%, and 0% respectively, all not significantly different from those of Group B (648.9 +/- 521.1) ml, (36.4 +/- 21.9) g/L, 2.1%, and 1.4% respectively, all P > 0.05. Aspirin is as effective as LMWH in venous thromboembolism prophylaxis after total joint arthroplasty. In addition, aspirin is cheap, administered orally, well tolerated, without necessity for surveillance, and with good compliance and potential of prevention of cardio-cerebrovascular events.

Aspirin Use and Outcomes in a Community-Based Cohort of 7352 Patients Discharged After First Hospitalization for Heart Failure

The safety of aspirin in heart failure (HF) has been called into question, particularly in those patients (1) without coronary disease, (2) with renal dysfunction, or (3) treated with low-dose angiotensin-converting enzyme (ACE) inhibitors and high-dose aspirin. We examined prescription patterns and outcomes (all-cause mortality and/or HF readmission) in patients discharged from 103 Canadian hospitals between April 1999 and March 2001 after a first hospitalization for HF. Of 7352 patients with HF (mean age, 75 years; 44% without coronary disease and 29% with renal dysfunction), 2785 (38%) died or required HF readmission within the first year. Compared with nonusers, aspirin users were no more likely to die or require HF readmission (hazard ratio [HR], 1.02 [0.91 to 1.16]), even in patients without coronary disease (HR, 0.98 [0.78 to 1.22]) or patients with renal dysfunction (HR, 1.13 [0.94 to 1.36]). On the other hand, users of ACE inhibitors were less likely to die or require HF readmission (HR, 0.87 [0.79 to 0.96]), even if they were using aspirin (HR, 0.86 [0.77 to 0.95]). There were no dose-dependent interactions between aspirin and ACE inhibitors. In this observational study, aspirin use was not associated with an increase in mortality rates or HF readmission rates, and aspirin did not attenuate the benefits of ACE inhibitors, even in patients without coronary disease, patients with renal dysfunction, or patients treated with high-dose aspirin and low-dose ACE inhibitors.

Aspirin for the Control of Platelet Activation and Prevention of Thrombosis in Essential Thrombocythemia and Polycythemia Vera: Current Insights and Rationale for Future Studies

Polycythemia vera and essential thrombocythemia are chronic myeloproliferative disorders characterized by a relatively benign clinical course that may be complicated by arterial and venous thromboses. A thrombotic diathesis often manifests at diagnosis or in the preclinical phase of the myeloproliferative disease. Peculiar microcirculatory disturbances such as erythromelalgia and visual and hearing symptoms also commonly occur in these patients, and are highly responsive to aspirin. In a placebo-controlled trial in relatively low-risk polycythemic subjects, low-dose aspirin recently was shown to reduce the incidence of both arterial and venous thrombosis with a limited increase of the hemorrhagic risk. Due to its favorable benefit/risk profile, low-dose aspirin should be prescribed to all patients with polycythemia vera who have no contraindication to this treatment. Future studies should assess primarily the efficacy and safety of aspirin in essential thrombocythemia, and test the possible use of more aggressive antithrombotic strategies in high-risk polycythemic patients.

Pharmacology update: daily aspirin—therapy?

More than 50 randomized trials have documented the efficacy and safety of aspirin as an antiplatelet agent and a cardiovascular drug. However, the optimal dose for preventing coronary and cerebral thrombosis has long been a cause of debate. For patients with ischaemic heart disease the range recommended for the prevention of a secondary event, based on strong clinical evidence, is 75–160 mg aspirin/day. For patients with cerebrovascular disease, recommendations range from 30–1300 mg/day. If these patients require a higher dose of aspirin it suggests that a different mechanism of action is involved. This paper considers hypotheses and reports the findings of recent clinical trials. The SALT study compared aspirin with placebo in 1360 patients with TIA or minor ischaemic stroke. It showed an 18% reduction in the risk of stroke or death in patients receiving 75 mg aspirin/day. Five other trials of 55,000 patients with ischaemic cerebrovascular disease compared the protective effect of aspirin (range 30–300 mg/day) with placebo, clopidogrel, or oral anticoagulants. Aspirin was better than placebo, safer than oral anticoagulants, and no different from clopidogrel. The implications of these findings are discussed. Mechanistic studies and randomized clinical trials strongly suggest that the mechanism of action and dose requirement of the antithrombotic effect of aspirin in patients with cerebrovascular disease is the same as that for ischaemic heart disease.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials