The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials.

PURPOSE: To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy. METHODS: A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use. RESULTS: At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77-0.98) and non-statin users (aHR 0.80, 95% CI 0.74-0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant. CONCLUSION: Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.

The Treatment Effect of an ACE-Inhibitor Based Regimen with Perindopril in Relation to Beta-Blocker use in 29,463 Patients with Vascular Disease: a Combined Analysis of Individual Data of ADVANCE, EUROPA and PROGRESS Trials.

INTRODUCTION: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. METHODS: In this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. RESULTS: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71-0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65-0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68-0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75-1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. CONCLUSIONS: These data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.

The role of insulin therapy and glucose normalisation in patients with acute coronary syndrome.

Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose-insulin-potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemia improves outcome in patients with AMI, achievement of glucose regulation is difficult and carries the risk of hypoglycaemia. More research is needed to determine the optimal glucose target levels in AMI and to investigate whether computerised glucose protocols and continuous glucose sensors can improve safety and efficacy of IGL.

Encouraging survival rates in patients with acute myocardial infarction treated with an intra-aortic balloon pump.

OBJECTIVE: To evaluate a 30-day and long-term outcome of patients with acute myocardial infarction (AMI) treated with intra-aortic balloon pump (IABP) counterpulsation and to identify predictors of a 30-day and long-term all-cause mortality. METHODS: Retrospective cohort study of 437 consecutive AMI patients treated with IABP between January 1990 and June 2004. A Cox proportional hazards model was used to identify predictors of a 30-day and long-term all-cause mortality. RESULTS: Mean age of the study population was 61 ± 11 years, 80% of the patients were male, and 68% had cardiogenic shock. Survival until IABP removal after successful haemodynamic stabilisation was 78% (n = 341). Cumulative 30-day survival was 68%. Median follow-up was 2.9 years (range, 6 months to 15 years). In patients who survived until IABP removal, cumulative 1-, 5-, and 10-year survival was 75%, 61%, and 39%, respectively. Independent predictors of higher long-term mortality were prior cerebrovascular accident (hazard ratio (HR), 1.8; 95% confidence interval (CI), 1.0-3.4), need for antiarrhythmic drugs (HR, 2.3; 95% CI, 1.5-3.3), and need for renal replacement therapy (HR, 2.3; 95% CI, 1.2-4.3). Independent predictors of lower long-term mortality were primary percutaneous coronary intervention (PCI; HR, 0.6; 95% CI, 0.4-1.0), failed thrombolysis with rescue PCI (HR, 0.5; 95% CI, 0.3-0.9), and coronary artery bypass grafting (HR, 0.3; 95% CI, 0.1-0.5). CONCLUSIONS: Despite high in-hospital mortality in patients with AMI treated with IABP, a favourable number of patients survived in the long-term. These results underscore the value of aggressive haemodynamic support of patients throughout the acute phase of AMI.

Process of care partly explains the variation in mortality between hospitals after peripheral vascular surgery.

OBJECTIVES: The aim of this study is to investigate whether variation in mortality at hospital level reflects differences in quality of care of peripheral vascular surgery patients. DESIGN: Observational study. MATERIALS: In 11 hospitals in the Netherlands, 711 consecutive vascular surgery patients were enrolled. METHODS: Multilevel logistic regression models were used to relate patient characteristics, structure and process of care to mortality at 1 year. The models were constructed by consecutively adding age, sex and Lee index, then remaining risk factors, followed by structural measures for quality of care and finally, selected process of care parameters. RESULTS: Total 1-year mortality was 11%, ranging from 6% to 26% in different hospitals. Large differences in patient characteristics and quality indicators were observed between hospitals (e.g., age>70 years: 28-58%; beta-blocker therapy: 39-87%). Adjusted analyses showed that a large part of variation in mortality was explained by age, sex and the Lee index (Akaike's information criterion (AIC)=59, p<0.001). Another substantial part of the variation was explained by process of care (AIC=5, p=0.001). CONCLUSIONS: Differences between hospitals exist in patient characteristics, structure of care, process of care and mortality. Even after adjusting for the patient population at risk, a substantial part of the variation in mortality can be explained by differences in process measures of quality of care.

The rationale and design of the PERindopril GENEtic association study (PERGENE): a pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. METHODS: The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40 degrees C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). CONCLUSION: The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease.

Variation between hospitals in patient outcome after stroke is only partly explained by differences in quality of care: results from the Netherlands Stroke Survey.

BACKGROUND AND PURPOSE: Patient outcome is often used as an indicator of quality of hospital care. The aim of this study is to investigate whether there is a straightforward relationship between quality of care and outcome, and whether outcome measures could be used to assess quality of care after stroke. METHODS: In 10 centres in The Netherlands, 579 patients with acute stroke were prospectively and consecutively enrolled. Poor outcome was defined as a score on the modified Rankin scale >or=3 at 1 year. Quality of care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed proportions of patients with poor outcome with expected proportions, after adjustment for patient characteristics and quality of care parameters. RESULTS: A total of 271 (47%) patients were dead or disabled at 1 year. Poor outcome varied across the centres from 29% to 78%. Large differences between centres were also observed in clinical characteristics, prognostic factors and quality of care. For example, between hospital quartiles based on outcome, age >or=70 years varied from 50% to 65%, presence of vascular risk factors from 88% to 96%, intravenous fluids when indicated from 35% to 81%, and antihypertensive therapy when indicated from 60% to 85%. The largest part of variation in patient outcome between centres was explained by differences in patient characteristics (Akaike's Information Criterion (AIC) = 134.0). Quality of care parameters explained a small part of the variation in patient outcome (AIC = 5.5). CONCLUSIONS: Patient outcome after stroke varies largely between centres and is, for a substantial part, explained by differences in patient characteristics at time of hospital admission. Only a small part of the hospital variation in patient outcome is related to differences in quality of care. Unadjusted proportions of poor outcome after stroke are not valid as indicators of quality of care.

[Differences between hospitals in outcome after a stroke are only partially explained by differences in the quality of care]. / Verschillen tussen ziekenhuizen in uitkomst na een herseninfarct vooral verklaard door patiëntkenmerken en slechts ten dele door verschillen in de kwaliteit van zorg.

OBJECTIVE: To determine the extent to which the outcome of stroke patients stroke is correlated with patient characteristics and care process parameters, and to determine whether outcome measures can be used to measure the quality of hospital care provided for these patients. DESIGN: Descriptive cohort study. METHODS: At 10 hospitals in the Netherlands, in the period October 2002-April 2003, patients with acute stroke were included in the study. Poor outcome was defined as dead or disabled at 1 year (a score on the modified Rankin scale > or = 3). Quality of the care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed numbers of patients with a poor outcome with expected numbers per hospital, after adjustment for patient characteristics and quality of care parameters. RESULTS: In total, 579 patients were included in the study, of which 271 (47%) were dead or disabled at 1 year. Poor outcome varied across the hospitals from 29 to 78%. The mean age was 70 years. There were large differences between hospitals with respect to patient characteristics and quality of care. Most of the differences in outcome between hospitals were explained by the differences in patient characteristics (Akaike's information criterion (AIC) = 134). Quality of care parameters explained just a small additional part of the variation in patient outcome (AIC = 5.5). CONCLUSIONS: Large differences between Dutch hospitals in the patient outcome after stroke could mostly be explained by differences in patient characteristics. Only a small part of the hospital variation in patient outcome was related to differences in quality of care. Therefore, outcome indicators cannot be regarded as valid performance indicators for care following a stroke.

[Guideline 'Cardiovascular Risk Management']. / Richtlijn 'cardiovasculair risicomanagement'.

The aim of the clinical practice guideline 'Cardiovascular risk management' is an integral approach to all relevant risk factors for cardiovascular disease (CVD) caused by atherothrombosis. Patients with CVD, diabetes mellitus type 2 (DM2), elevated blood pressure or cholesterol, men of 50 years or older who smoke and women of 55 years or older who smoke are eligible for assessment of relevant risk factors for CVD. All high-risk patients should receive lifestyle counselling. In patients with CVD the use of acetylsalicylic acid and often, depending on the specific disease, a beta-blocker or an angiotensin converting enzyme (ACE) inhibitor are recommended. The use of a statin is recommended if the LDL-cholesterol concentration is > or = 2.5 mmol/l. In patients with DM2, the use of statins is recommended if LDL-cholesterol is > or = 2.5 mmol/l and use of a blood pressure lowering drug with a systolic blood pressure > or = 140 mmHg, as well as glucose lowering drugs. In patients without CVD and DM2, the need for drug treatment will be determined by estimation of the absolute 10-year mortality risk of CVD. Treatment is recommended if this risk exceeds 10%. The treatment and follow-up plan will be determined individually, depending on the risk profile, morbidity, comorbidity and patient's preferences.

Real-time transthoracic three-dimensional echocardiography provides additional information of left-sided AV valve morphology after AVSD repair.

AIMS: The purpose of this study was to assess the feasibility of real-time 3D echocardiography (RT-3DE) data acquisition in adult patients after atrioventricular septal defect (AVSD) repair and to evaluate whether RT-3DE has additional value over 2D echocardiography, regarding morphology and function of the left-sided AV valve (LAVV). METHODS: Twenty consecutive patients with surgically corrected partial or complete AVSD were enrolled in this study. The 3DE data sets were acquired with the Hewlett-Packard Sonos 7500 echo system (Philips Medical Systems, Andover, MA, USA). Images were reviewed off-line with assistance of TomTec Echoview 5.2 software (TomTec Inc., Munich, Germany) by experienced observers. En face reconstructions, from, respectively, the ventricular and atrial view, were made to evaluate the LAVV morphology and motion. RESULTS: 3DE reconstruction of the LAVV was feasible in 17 of 20 patients (85%). Mean time of 3DE acquisition was 9+/-6 min. The quality of the 3DE images was optimal in 35%, good in 30%, sufficient in 20% and insufficient in 15%. Identification of the LAVV structures was importantly better facilitated from a ventricular view. Accurate identification of LAVV morphology was possible in all 17 patients (85%). Relationship of the LAVV and the abnormal position of the LVOT was easier to evaluate from the 3DE reconstructions than from 2D echo. CONCLUSION: This study demonstrate that RT-3DE is feasible in daily practice and provides new insight into the dynamic morphology of the left-sided AV valve and LVOT anatomy after AVSD repair.

Angiographic findings in patients with refractory unstable angina according to troponin T status.

BACKGROUND: The CAPTURE (C7E3 fab AntiPlatelet Therapy in Unstable REfactory angina) trial enrolled patients with refractory unstable angina and documented a therapeutic benefit for abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, that was particularly evident in patients with elevated troponin T (TnT) levels. In the current study, we related the angiographic data to the TnT status of the CAPTURE patients. METHODS AND RESULTS: In 853 patients, angiographic data at baseline and 18 to 24 hours after treatment were available and assessed by an Angiographic Committee with respect to TIMI flow, lesion severity, and visibility of thrombus. TnT levels >0.1 microg/L were found in 30.9% of the patients. Before randomization, thrombus was visible in 14.6% of TnT-positive patients (TnT levels >0.1 microg/L) and 4.2% of TnT-negative patients (P=0.004). Complex lesion characteristics B2+/C (72.0% versus 53.9%; P<0.001) and TIMI flow <2 (15.6% versus 5. 1%; P<0.001) were more frequent in TnT-positive patients. Abciximab was effective with respect to reduction of visible thrombus, increase of TIMI flow, and reduction of cardiac events in TnT-positive patients only. Multivariate analysis identified TnT status, but not angiographic findings, as an independent predictor for both outcome and efficacy of treatment with abciximab. CONCLUSIONS: Complex lesion characteristics and visible thrombus formation at baseline were significantly linked to TnT elevation. However, TnT status was a more powerful predictor of increased cardiac risk and efficacy of treatment with abciximab than either. Relative to the angiogram, TnT can thus be considered a more sensitive marker for the underlying pathology, identifying patients with unstable angina who will particularly benefit from antiplatelet treatment.

Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention.

BACKGROUND: Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. METHODS AND RESULTS: We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. CONCLUSIONS: There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.

Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one-year survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV--Acute Coronary Syndrome) Trial.

BACKGROUND: This study was designed to investigate long-term effects of the glycoprotein IIb/IIIa inhibitor abciximab in patients with acute coronary syndrome without ST elevation who were not scheduled for coronary intervention. METHODS AND RESULTS: A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. They were randomized to abciximab bolus and 24-hour infusion, abciximab bolus and 48-hour infusion, or matching placebo. The overall 1-year mortality rate was 8.3% (649 patients). One-year mortality was 7.8% in the placebo group and 8.2% in the 24-hour and 9.0% in the 48-hour abciximab infusion group. Compared with placebo, the hazard ratio for the 24-hour infusion of abciximab was 1.1 (95% CI 0.86 to 1.29), and for the 48-hour infusion, it was 1.2 (95% CI 0.95 to 1.41). The lack of benefit of abciximab was observed in every subgroup studied. Patients with negative troponin or elevated C-reactive protein had a higher mortality rate after treatment with abciximab for 48 hours than with placebo: 8.5% versus 5.8% in those with negative troponin (P=0.02), 16.3% versus 12.1% in those with elevated C-reactive protein (P=0.04). CONCLUSIONS: Compared with placebo, abciximab did not provide any survival benefit at 1 year in patients admitted with an acute coronary syndrome with ST depression and/or elevated troponin who were not scheduled to undergo early coronary revascularization. In subgroups of patients, in particular those with low cardiac troponin or elevated C-reactive protein, abciximab was associated with excess mortality.

Attenuation of rebound ischemia after discontinuation of heparin therapy by glycoprotein IIb/IIIa inhibition with eptifibatide in patients with acute coronary syndromes: observations from the platelet IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

Background- A reactivation of ischemia after the discontinuation of intravenous heparin in acute coronary syndromes has been described. The effect of glycoprotein IIb/IIIa blockade on heparin rebound is unknown. Methods and Results- Patients with acute coronary syndromes who received heparin therapy but not initial revascularization in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial were analyzed. Rates of death or myocardial (re)infarction while on heparin therapy and in 12-hour periods in the 2 days after heparin discontinuation were compared between eptifibatide and placebo. There was no difference between study groups in event rates during heparin infusion. In the 12 hours after heparin discontinuation, there was a 2.5-fold increase in all events, an 8-fold increase in death, and a 2-fold increase in myocardial infarction. However, in the 12 hours after heparin discontinuation, there was a significantly lower rate of events (1.68% versus 2.53%, P=0.03) and death (0.77% versus 0.21%, P=0.002) in the eptifibatide group compared with the placebo group. When only considering patients who were on study drug at the time of heparin discontinuation, the reduction in the combined end point was marginally significant, but the difference in the rate of death remained significant (0.68% versus 0.06%, P=0.004). In logistic regression analyses, the multivariate predictors of rebound events were the duration of heparin therapy, age, North American site, and lack of eptifibatide treatment. Conclusions- An increase in death or myocardial infarction occurs in the 12 hours after heparin discontinuation in patients with acute coronary syndromes. This rebound is attenuated by glycoprotein IIb/IIIa inhibition with eptifibatide.

Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

BACKGROUND: A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. METHODS AND RESULTS: Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase-MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% (P=0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P=0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. CONCLUSIONS: Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.

Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease.The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators.

BACKGROUND: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized. METHODS AND RESULTS: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to

Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators.

BACKGROUND: Appropriate treatment policies should include an accurate estimate of a patient's baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation. METHODS AND RESULTS: We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81). CONCLUSIONS: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process.

Early percutaneous coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. PURSUIT Investigators.

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the composite end point of death or myocardial infarction (MI) in patients with acute coronary syndromes. There is uncertainty about whether this effect is confined to patients who have percutaneous coronary interventions (PCIs) and whether PCIs further prevent death or MI in patients already treated with GP IIb/IIIa antagonists. METHODS AND RESULTS: PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs were performed according to physician practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days. Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI preceded early PCI. In patients censored for PCI across the 30-day period, there was a significant reduction in the primary composite end point in eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI propensity, there was no evidence that eptifibatide treatment effect differed between patients with or without early PCI (P for interaction=0.634). PCI was not associated with a reduction of the primary composite end point but was associated with a reduced (nonspecified) composite of death or Q-wave MI. This association disappeared after adjustment for propensity for early PCI. CONCLUSIONS: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively.

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.