Prior Aspirin Use Research Articles

Ornithine decarboxylase (Odc)-1 gene polymorphism effects on baseline tissue polyamine levels and adenoma recurrence in a randomized phase III adenoma prevention trial of DFMO + sulindac versus placebo

1502 Background: The Odc G315A single nucleotide polymorphism (SNP) affects Odc transcription and favorably modifies aspirin's effect on colorectal adenoma risk. Treatment with the polyamine-inhibitory regimen difluoromethylornithine (DFMO) and sulindac has been shown to markedly decrease adenoma recurrence compared to placebo. Here we investigate modifying effects of the Odc G315A SNP on baseline tissue polyamine content and polyp recurrence after treatment with DFMO + sulindac or placebo. Methods: Data from the randomized phase III DFMO (500mg daily) + sulindac (150mg daily) colorectal adenoma prevention trial were analyzed. Odc genotyping was performed on patient-derived genomic DNA samples using allele-specific TaqMan probes. Baseline rectal tissue polyamine content was determined via HPLC. Clinicopathologic data were compared after stratification by genotype. Fisher's exact test or χ2 tests for independence were used for comparisons of categorical variables. Two-tailed t-tests or Kruskal-Wallis nonparametric analysis of variance were used for numerical comparisons between groups. Results: Data were available for 122 of 375 study patients. Odc genotype distribution was 54% GG, 5% AA, 41% GA. Patients with any Odc A- allele (AA/GA) were similar in age, gender, race, and prior aspirin use across treatment arms, as were Odc GG patients. Odc GG vs AA/GA patients had significantly higher median baseline rectal tissue putrescine (0.52 vs 0.31 nmol/mg protein, P=0.046) and spermidine (2.10 vs 1.65 nmol/mg protein, P=0.011) content. Among Odc AA/GA patients, 7/26 patients (27%) had recurrent adenoma in the DFMO + sulindac arm vs 14/30 patients (47%) in the placebo arm (P=0.13, absolute risk difference=20%). Among Odc GG patients, 6/39 patients (15%) had recurrent adenoma in the DFMO + sulindac arm compared with 14/27 (52%) placebo patients (P=0.002, absolute risk difference=37%). Conclusions: DFMO + sulindac treatment lowers the incidence of recurrent adenomata among adenoma patients, with pronounced effects observed among Odc homozygous GG patients. This may be related to baseline tissue polyamine differences across these genetically-defined groups. No significant financial relationships to disclose.

Failure of aspirin to prevent myocardial infarction and adverse outcome during follow-up—a large series of all-comers

Background. Aspirin has been used for secondary prevention of myocardial infarction (MI) in individuals with coronary disease. Although supported by several large controlled trials, aspirin prevents only a portion of recurrent events.Aim and method. We set out to study the prevalence of long-term aspirin use prior to admission for MI and its significance for medium-term event-free survival; 998 consecutive patients with acute MI admitted to a tertiary center were included in the study.Results. Nearly half (42.4%) of all patients reported long-term use of low-dose aspirin prior to the index event. Prior aspirin use was associated with a 50% increase in the risk of both the combined end point of recurrent unstable angina, recurrent myocardial infarction, stroke, or death (OR 1.49; 95% CI 1.12–2.00, P=0.006) and mortality (OR 1.50; 95% CI 1.03–2.17, P=0.03) during 10-month follow-up. Prior aspirin use was not associated with an increased frequency of added antithrombotic therapy at discharge.Conclusions. We have found that prior aspirin use is common in patients hospitalized for acute MI. Individuals already on aspirin had increased risk of recurrent ischemic events and all-cause mortality during the 10-month follow-up after their index MI.

2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention

2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention

The Role of Aspirin Resistance in the Treatment of Acute Coronary Syndromes

The TIMI Risk Score recognizes prior aspirin use as an independent risk factor for adverse outcomes in subjects presenting with an acute coronary syndrome. The etiology of this increased risk awaits clarification, but prior aspirin use may be associated with altered thrombus composition which is more resistant to current treatment modalities as compared to thrombus formation in subjects without prior aspirin use. Post hoc analysis of acute coronary syndrome trials has shown that prior aspirin users treated with unfractionated heparin are at particularly high risk. The addition of glycoprotein IIb/IIIa receptor inhibitor to unfractionated heparin or substitution of low-molecular-weight heparin significantly improves outcomes in prior aspirin users. The prognostic significance of prior aspirin use in acute coronary syndromes has important implications not only in clinical practice, but also in the design and interpretation of clinical trials.

Prior Statin Use Reduces Mortality in Intracerebral Hemorrhage

To assess the impact of blood glucose, coagulopathy, seizures and prior statin and aspirin use on clinical outcome following intracerebral hemorrhage (ICH). Intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes with mortality rates approaching 50%. Glasgow Coma Scale (GCS), ICH volume, age, pulse pressure, ICH location, intraventricular hemorrhage (IVH) and hydrocephalus are known to impact 30-day survival following ICH and are included in various prediction models. The role of other clinical variables in the long-term outcome of these patients is less clear. Records of consecutive ICH patients admitted to The Johns Hopkins Hospital from 1999 to 2006 were reviewed. Patients with ICH related to trauma or underlying lesions (e.g. brain tumors, aneurysms, arterio-venous malformations) and of infratentorial location were excluded. The impact of admission blood glucose, coagulopathy, seizures on presentation and prior statin and aspirin use on 30-day mortality and functional outcomes at discharge was assessed using dichotomized Modified Rankin Scale (dMRS) and Glasgow Outcomes scale (dGOS). Other variables known to impact outcomes that were included in the multiple logistic regression analysis were age, admission GCS, pulse pressure, ICH volume, ICH location, volume of IVH and hydrocephalus. A total of 314 patients with ICH were identified, 125 met inclusion criteria. Patients' age ranged from 34 to 90 years (mean 63.5), 57.6 % were male. Mean ICH volume was 32.09 cc (range 1-214 cc). Following multiple logistic regression analysis, prior statin use (P = 0.05) was found to be associated with decreased mortality with a greater than 12-fold odds of survival while admission blood glucose (P = 0.023) was associated with increased 30-day mortality. Coagulopathy, seizures on presentation, and prior aspirin use had no significant impact on 30-day mortality or outcomes at discharge in our study cohort. The significant association of prior statin use with decreased mortality warrants prospective evaluation of the use of statins following ICH.

Does Prior Aspirin Use Reduce Stroke Mortality?

Millions of people around the world regularly consume aspirin, but its value in determining stroke severity is still not clear. It has been stated that prior aspirin use might reduce the severity of ischemic stroke by reducing the size of fibrin-platelet emboli or by ameliorating platelet hyperaggregability that occurs in the microcirculation. However there are only few large studies focusing on the early outcome of stroke patients including both ischemic stroke and primary intracerebral hemorrhage patients with prior aspirin therapy. We retrospectively analyzed the medical records of 2509 consecutive stroke patients who were hospitalized in the 2nd Neurology Clinic of Haydarpaşa Numune Education and Research Hospital, Istanbul, Turkey, during the period of 1993-2003. We compared the early mortality rates in the patients with prior aspirin use versus the patients without. Of the patients without prior aspirin use, 20.1% died during the first 3 weeks of the stroke, while only 11.5% of the patients with prior aspirin use died during the same period. The difference in early mortality rate between 2 groups was extremely significant (P = 0.0008). Logistic regression analysis indicated that aspirin use was a significant (P < 0.01) and independent predictor of early stroke mortality. Daily low dose (100-300 mg) aspirin has a protective effect in reducing the risk of early death in stroke.

Effects of Conjugated Equine Estrogen on Stroke in the Women’s Health Initiative

The Women's Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database. The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10,739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin. CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.

Prior clopidogrel use and outcome of acute coronary syndrome

Background Prior aspirin use has been associated with poorer outcome in acute coronary syndrome, and forms part of the TIMI Risk Score. It is not known if prior use of clopidogrel is associated with similar risk. Aim To assess if prior clopidogrel use is associated with higher risk in acute coronary syndrome. Participants Participants were 869 consecutive admissions to a Scottish district general hospital with suspected acute coronary syndrome. Methods Incidence of death, recurrent myocardial infarction or urgent percutaneous intervention at 2 weeks was recorded. Odds ratios for sub-groups on clopidogrel, aspirin or neither were calculated. Results Odds ratios were: clopidogrel 1.46 (95% ci 0.62–3.33), aspirin 1.09 (95% ci 0.64–1.85), neither 0.91 (95% ci 0.53–1.54). Conclusion No definite association was shown between clopidogrel use and outcome but there was a trend towards increased risk of major acute coronary events.

Prior Aspirin Use and Outcomes in Elderly Patients Hospitalized With Acute Myocardial Infarction

We sought to assess the association between prior aspirin use and mortality, all-cause readmission, and condition-specific readmission at one month and six months in a national sample of Medicare beneficiaries hospitalized with a confirmed myocardial infarction (MI). Prior aspirin use is considered a marker of higher risk in patients with MI, yet the prognostic significance of this factor has been debated. Medicare beneficiaries > or =65 years old hospitalized with MI were evaluated to determine whether there was an association between prior aspirin use and mortality (n = 118,992), all-cause readmission, and condition-specific readmission (n = 78,975) at one month and six months. One-third of the patients (n = 39,531, 33.2%) were using aspirin before admission. Those with prior aspirin use had significantly lower mortality at one month (16.1% vs. 19.0%, p < 0.0001) and six months (24.7% vs. 27.5%, p < 0.0001). After multivariable adjustment, prior aspirin use was found to be associated with a lower risk of one-month (relative risk ratio 0.93, 95% confidence interval [CI] 0.90 to 0.96) and six-month mortality (hazard ratio 0.94, 95% CI 0.91 to 0.96). Prior aspirin use tended to reduce all-cause or coronary artery disease readmissions at one month or six months. Prior aspirin use is not a marker of increased mortality in patients > or =65 years old hospitalized with MI.

Correlation between the TIMI risk score and high-risk angiographic findings in non–ST-elevation acute coronary syndromes: Observations from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial

The TIMI risk score for unstable angina and non-ST elevation myocardial infarction is an effective tool for predicting the risk of death and ischemic events among patients with non-ST elevation acute coronary syndromes, as well as for identifying those who are likely to benefit most from low-molecular-weight heparin and glycoprotein IIb/IIIa inhibition. To explore the pathobiologic basis for this interaction, we evaluated the relationship between the risk score, assessed at presentation, and angiographic findings among patients with non-ST elevation acute coronary syndromes. Angiographic data regarding thrombus, epicardial flow, and lesion severity were available for 1491 patients from the angiographic substudy of PRISM-PLUS. Patients with risk scores of 5 to 7 (N = 435) were more likely to have a severe culprit stenosis (81% vs 58%, P < .001) and multivessel disease (80% vs 43%, P < .001) compared to those with scores of 0 to 2 (N = 220). The probability of left main disease (P = .01), visible thrombus, and impaired flow in the culprit lesion also increased progressively with rising risk scores (P < .001). Of the risk indicators that comprise the score, history of coronary disease, advanced age, and ST changes showed the strongest association with severe epicardial disease. Positive biomarkers of necrosis, ST changes, and prior aspirin use emerged as stronger correlates of visible thrombus and/or impaired culprit artery flow. The TIMI risk score identifies patients who are more likely to have intracoronary thrombus, impaired flow, and increased burden of coronary atherosclerosis. These findings likely explain in part the particular benefit of potent antithrombin and antiplatelet agents among patients with higher risk scores.

Prior aspirin use may increase the risk of intracerebral haemorrhage following alteplase treatment

Prior aspirin use may increase the risk of intracerebral haemorrhage following alteplase treatment

Grade 3 ischemia on admission and absence of prior beta-blockade predict failure of ST resolution following thrombolysis for anterior myocardial infarction

Background ST segment resolution (STR) is a strong predictor of outcome following thrombolysis. If failure of STR could be predicted on admission, better selection of treatment may be possible. Among patients given reperfusion, those with terminal QRS distortion (grade 3 ischemia) have larger infarcts, but the mechanism underlying this association is unclear. Whether grade 3 ischemia on admission can predict STR is unknown. Methods We studied 180 consecutive patients given thrombolysis for a first anterior acute myocardial infarction (AMI). Multiple variables available on admission were analyzed as predictors of STR at 1, 2, and 24 h and as predictors of the need for rescue percutaneous coronary intervention (PCI). Results Multivariate predictors of failure of STR were: for 1 h: extent of ST elevation (OR: 1.09 [1.01–1.18]); for 2 h: no previous use of beta-blockers (OR: 4.71 [1.56–13.98]) and grade 3 ischemia (OR: 6.77 [3.27–13.95]); for 24 h: previous use of aspirin (OR: 6.70 [1.31–34.01]) and grade 3 ischemia (OR: 29.44 [7.30–118.1]). Grade 3 ischemia had a strong positive predictive value for failure of STR at 1 and 2 h and was the strongest predictor of the need for rescue PCI. Conclusions Grade 3 ischemia on admission is the strongest independent predictor of failure to achieve myocardial reperfusion after thrombolysis. This association may underlie the larger infarcts associated with grade 3 ischemia. Other predictors of reperfusion failure are the extent of ST segment elevation, prior use of aspirin and no prior use of beta-blockers.

Influence of aspirin on outcome following aneurysmal subarachnoid hemorrhage

Previous studies have indicated an increased incidence of death in patients with subarachnoid hemorrhage (SAH) who are currently receiving anticoagulation therapy. The significance of previous aspirin use in patients with SAH is unknown. The authors analyzed the effects of prior aspirin use on clinical course and outcomes following aneurysmal SAH. The medical records of 305 patients with angiogram-confirmed aneurysmal SAH who consecutively presented to our institution between 1990 and 1997 within 7 days of ictus were analyzed. Twenty-nine (9.5%) of these patients had a history of regular aspirin use before onset of the SAH. The Glasgow Outcome Scale (GOS) was used to measure patient outcome at the longest available follow up. Aspirin users were older on average than nonusers (59 years of age compared with 53 years; p = 0.018). The mean admission Hunt and Hess grades of patients with and without aspirin use were similar (2 compared with 2.3; p = 0.51). Two trends, which did not reach statistical significance, were observed. 1) The rebleeding rate in aspirin users was 14.3%, compared with a 4.7% rebleeding rate in nonusers (p = 0.06). 2) Permanent disability from vasospasm was less common among aspirin users (23% compared with 50%; p = 0.069). Outcomes did not differ between aspirin users and nonusers (mean GOS Score 3.83 compared with GOS Score 3.86, respectively; p = 0.82). Despite trends indicating increased rebleeding rates and a lower incidence of permanent disability due to delayed ischemic neurological deficits, there was no significant effect of previous aspirin use on overall outcome following aneurysmal SAH. Based on these preliminary data, the presence of an intracranial aneurysm is not a strict contraindication to aspirin use.

Thromboxane and prostacyclin biosynthesis in patients with acute spontaneous intracerebral hemorrhage

Objective: Elevated levels of 11-dehydrothromboxane B 2 (11-dehydro-TXB 2) excreted in urine have been observed in acute ischemic stroke. This marker of platelet activation has not been investigated in patients with acute spontaneous intracerebral hemorrhage (ICH). Methods: We examined 43 patients with spontaneous ICH and 23 controls. Urinary excretion rates of 11-dehydro-TXB 2, 2,3-dinor-thromboxane B 2 (2,3 dinor-TXB 2) and 2,3-dinor-6-ketoprostaglandin F 1α (2,3-dinor-PGF 1α) during the first week and at 3 months after ICH were compared between patients who had or had not used aspirin and controls. Results: On admission, ICH patients without aspirin use had significantly higher urinary levels of 11-dehydro-TXB 2 ( p<0.001), 2,3-dinor-TXB 2 ( p<0.001) and 2,3-dinor-PGF 1α ( p=0.019) than controls. Aspirin users had significantly lower urinary levels of these metabolites than nonusers. The metabolite levels of aspirin users on admission did not significantly differ from those of controls. The differences between aspirin users and nonusers leveled off during the following 3–5 days, however, as the blocking effect of aspirin on the production of TXA 2 and PGI 2 ceased. Three months after ICH, the metabolite excretion levels in all the patients were similar to those in nonusers of aspirin on admission. On admission, aspirin users had longer bleeding times ( p=0.032) than nonusers, but aspirin use did not associate with impaired recovery or hematoma enlargement. Conclusions: Urinary excretion levels of 11-dehydro-TXB 2, 2,3-dinor-TXB 2 and 2,3-dinor-PGF 1α were higher in patients with acute ICH than in controls. The levels in aspirin users were equally low as in controls but rose to the levels of the other patients within a few days. The metabolite levels remained high 3 months after ICH in all patients. Prior use of aspirin did not seem to cause hematoma enlargement.

Non-st–elevation acute coronary syndrome in the elderly: treatment strategies and 30-day outcome

Background The purpose of this study was to assess the current care of elderly patients with non-ST–elevation acute coronary syndrome (ACS), with particular regard to the rate of use of antiplatelet drugs and the type of strategy, aggressive or conservative, in a population of consecutive patients admitted to 76 Coronary Care Units in Italy. Methods Prospective registry of patients admitted to Coronary Care Units with a diagnosis of non-ST–elevation ACS during a 2-month period. Thirty-day follow-up was available in all patients. Results Of 1581 patients enrolled in the registry, 564 were 75 years or older. As compared with the 1017 younger patients, elderly patients had a greater prevalence of female sex (42% vs 27%, P < .001), hypertension (70% vs 59%, P < .001), prior myocardial infarction (MI) (41% vs 29%, P < .001), prior angina (18% vs 13%, P < .01), prior use of aspirin (49% vs 39%, P < .001), ST-segment depression (54% vs 43%, P < .001), and troponin positivity (66% vs 59%, P < .05). The higher-risk profile of elderly patients was confirmed by the greater number of patients with a high TIMI risk score (37% vs 22%, P < .001). GPIIb/IIIa inhibitors were less frequently used in elderly patients ( P < .05). An aggressive strategy (coronary arteriography within 4 days of admission, followed by revascularization, if feasible) was adopted in 39% elderly patients and in 56% younger patients ( P < .001). An interventional procedure within 30 days was performed in 30% of elderly patients and 48% of younger patients ( P < .001). Elderly patients had a more unfavorable 30-day outcome compared with younger ones, as shown by the higher rates of death (6.4% vs 1.7%), acute myocardial infarction (7.1% vs 5%), and stroke (1.3% vs 0.5%). Multivariate analysis of the elderly group identified a conservative strategy (OR, 2.31; 95% CI, 1.20 to 4.48) and a diagnosis of non–Q-wave MI (OR, 2.27; 95% CI, 1.32 to 3.93) as independent predictors of 30-day events. Conclusions The elderly represent a very high-risk subgroup among patients with non-ST–elevation ACS, with a nearly 4-fold as high 30-day death rate as that of younger patients. These data call for a greater attention to such population, both in terms of an improved representation in clinical research and of the assessment of the outcome of different strategies in appropriately designed randomized trials.

C-reactive protein levels as an early predictor of 30-day mortality in patients with acute myocardial infarction

Background: In patients with unstable angina, elevated C-reactive protein (CRP) has been shown to predict recurrent coronary events. However, little data is available on the prognostic value of CRP in acute myocardial infarction (AMI), and its relation to measures of infarct size. Methods: CRP was measured within 24-h of symptoms onset in a prospective series of 348 consecutive patients (mean age 62 + 13 y, men 76%) with AMI (260 with ST-elevation AMI). Echocardiographic examination was performed on day 2 or 3. Thirty-day mortality was evaluated using Cox proportional-hazards model wtth the following covariates: age, gender, prior aspirin use, Killip class, diabetes, peak CK. SBP 2.2 mg/UL) had higher peak CK (1999 t 166 vs 1762 * 116, p = 0.01) and higher echocardiographic wall motion score index (1.6 * 0.4 vs 1.5 + 0.4, p < 0.0001). Kaplan-Meier surwal wives indicated that patients with CRP levels in the upper tertile were at Increased risk of 30.day mortality (Figure). In a Cox’s multivariate analysis, CRP level in the upper tertile was a significant and independent predictor of 30-day mortality (Relative Risk = 3.2, 95% Cl 1.2-6.2, p = 0.007). Conclusion: CRP level on admission is a powerful predictor of 30-day mortality in patients with AMI independent of infarct size and other traditional predictors of outcome.

Prior aspirin use in unstable angina patients with modified plasma inflammatory markers and endothelial nitric oxide synthase in neutrophils.

Prior use of aspirin in patients with acute coronary syndrome has been associated with a lower incidence of acute myocardial infarction. The aim of this study was to explore if prior aspirin therapy in unstable angina (UA) patients could modify systemic inflammatory markers such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) and the expression of endothelial nitric oxide synthase (eNOS) in neutrophils. Unstable angina was defined as transient S-T segment changes without significant increases in CK and CK-MB. We studied 50 consecutive patients admitted to hospital within 24 h after the onset of chest pain. The number of patients with prior aspirin was significantly higher (n = 32) than those not taking aspirin (n = 18) on admission. Plasma levels of IL-6 and ICAM-1 were significantly increased in the UA patients when compared with the healthy control volunteers (n = 20) used as a reference for normal values. Plasma levels of both IL-6 and ICAM-1 were reduced in patients taking aspirin. There were no differences in the plasma levels of TNF-alpha between the UA patients and the control volunteers. The eNOS protein expression was also higher in neutrophils from the UA patients taking aspirin than in those not taking aspirin. Patients taking aspirin before UA showed a lower systemic inflammatory response and higher eNOS protein expression in their neutrophils

Prior Aspirin Therapy, Subsequent Stroke Severity and Mortality and Relationship with Cardiovascular Risk Factors in Patients Admitted to Hospital with Acute Stroke

Objective: To investigate whether the prior use of aspirin has an association with the severity and mortality of subsequent stroke and its relationship with cardiovascular risk factors. Methods: This was a study of 296 patients, with a median age of 75 years, admitted to hospital with acute stroke. Data were collected on demography, risk factors, stroke syndromes, infarct size, parameters of stroke severity and acute-phase and 90-day mortality. Patients were categorised into aspirin (n = 95) and non-aspirin (n = 201) groups, depending on whether or not they had received prior aspirin therapy. Analysis was performed to study the relationship between prior aspirin therapy, cardiovascular risk factors, previous stroke and stroke mortality. Results: Patients in the aspirin group were more disabled prior to stroke (p < 0.001) and had a higher incidence of prior stroke (p < 0.001) and ischaemic heart disease (p < 0.001). There was insignificantly higher acute-phase and 90-day mortality in the aspirin group (p = 0.13 and 0.30, respectively) in all patients. There was significantly higher acute-phase mortality among patients with ischemic strokes in the aspirin group [p = 0.02; relative risk (RR) 2.26, 95% confidence interval (CI) 1.14–4.50] and non-significantly higher 90-day mortality (p = 0.08; RR 1.50, 95% CI 0.96–2.35). The significance did not persist when previous stroke was controlled for. Patients with pre-existing cardiac failure on aspirin had higher mortality (0.001) than did patients in the non-aspirin group. Conclusions: There was a trend for higher mortality in patients with ischaemic strokes on prior aspirin therapy. This may have been due to a higher incidence of cardiovascular disease in the aspirin group. Patients with cardiac failure on aspirin had higher mortality following a stroke.

Prior aspirin users with acute non-ST-elevation coronary syndromes are at increased risk of cardiac events and benefit from enoxaparin

Background The aim of this article was to investigate whether prior aspirin use in patients with acute coronary syndromes affects clinical outcome. The Efficacy Safety Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials have shown superiority of enoxaparin over unfractionated heparin (UFH) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the treatment effect of enoxaparin in the subset of patients reporting prior aspirin use has not been determined. Methods The rate of death, myocardial infarction, and urgent revascularization at days 8 and 43 after randomization was compared among patients who received aspirin within the week before randomization with those who did not receive aspirin in the TIMI 11B trial. A total of 3275 patients (84%) were prior aspirin users. Results The admission diagnosis was similar for prior and nonprior aspirin users. At both day 8 and day 43 the event rate was higher for prior aspirin users than for nonprior aspirin users (odds ratio 1.6 [1.24-2.08], P =.0004 at day 43), even after correction for baseline characteristics. Compared with those prior aspirin users taking UFH, enoxaparin-treated prior aspirin users had a reduced rate of the composite end point of death, myocardial infarction, and urgent revascularization at day 8 (odds ratio 0.82 [0.67-1.00], P =.046) and day 43 (odds ratio 0.83 [0.70-0.98], P =.032). Conclusion Patients with UA/NSTEMI and prior aspirin use had a 60% higher risk of death and cardiac ischemic events compared with nonprior aspirin users. On the basis of this subanalysis, enoxaparin is superior to UFH in all patients. In prior aspirin users the benefit is more clearly demonstrated. (Am Heart J 2001;141:566-72.)

Inter-regional differences and outcome in unstable angina; analysis of the international ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events.

Worldwide there is a large variation in outcome (death, myocardial infarction and recurrent myocardial infarction) in patients with unstable angina or non-Q wave myocardial infarction. These variations may be explained by differences in characteristics of the presenting patients. Here we describe differences in patient presentation, treatment protocols and outcome and we investigate their relationship using data from the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) trial. A total of 2981 patients from six countries which enrolled more than 100 patients were included in the present analysis: United States, Canada, Argentina, France, the Netherlands and United Kingdom. Logistic regression analysis was performed to determine the effect of baseline characteristics on regional outcome. At day 30, the lowest triple end-point rate, irrespective of study drug treatment, was noted in the Netherlands (18.9%) and the highest in Argentina (30.5%). A model including the variables age > or = 65 years, prior angina, diabetes, prior aspirin use, ECG changes at baseline and diagnosis of non-Q wave myocardial infarction and dummy variables for Argentina and France resulted in concordance of about 60%. Inter-regional differences in outcome in unstable angina and non-Q wave myocardial infarction patients can reasonably well be explained by differences in patient characteristics. However, other so far unidentified variables present in Argentina and France also contributed to differences in outcome and their effect warrants further investigation.