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Aims Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into heart failure pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters as well as with elevated left atrial pressure (LAP), in patients with HFrEF, to provide insights into underlying mechanisms. Methods and results In 173 patients with HFrEF, we performed 6-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7 (inter-quartile range: 2.5–2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular [left ventricular ejection fraction (LVEF), global longitudinal strain (GLS)] and left atrial function [left atrial reservoir strain (LASr)] and elevated LAP (E / e ʹ ratio >15) and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792, and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr, and E / e ʹ ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix. Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: cystatin-D, fibulin-5, and HSP40. Conclusion Circulating proteins show varying associations with different echocardiographic parameters in patients with HFrEF. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct. [ABSTRACT FROM AUTHOR]

Aims Oral glycoprotein IIb/IIIa inhibitors might enhance the early benefit of an intravenous agent and prevent subsequent cardiac events in patients with acute coronary syndromes. We assessed the safety and preliminary efficacy of 1 month treatment with three dose levels of the oral GP IIb/IIIa blocker lefradafiban in patients with unstable angina or myocardial infarction without persistent ST elevation.Methods The Fibrinogen Receptor Occupancy STudy (FROST) was designed as a dose-escalation trial with 20, 30 and 45mg lefradafiban t.i.d. or placebo. Five hundred and thirty-one patients were randomized in a 3:1 ratio to lefradafiban or placebo in a double-blind manner. Efficacy was assessed by the incidence of death, myocardial infarction, coronary revascularization and recurrent angina. Safety was evaluated by the occurrence of bleeding classified according to the TIMI criteria and by measuring clinical laboratory parameters.Results There was a trend towards a reduction in cardiac events with lefradafiban 30mg when compared with placebo and lefradafiban 20mg. The benefit was particularly apparent in patients with a positive (≥0·1ng.ml−1) troponin I test at baseline and less so in those with a negative test result. In patients receiving lefradafiban, the cardiac event rate decreased with increasing minimal levels of fibrinogen receptor occupancy. There was a dose-dependent increase in the incidence of bleeding: the composite of major or minor bleeding occurred in 1% of placebo patients, 5% of patients receiving lefradafiban 20mg and in 7% of patients receiving 30mg, with an excessive risk (15%) in the 45mg group which resulted in early discontinuation of this dose level. Gingival and arterial or venous puncture site bleedings were most common and accounted for more than 60% of all haemorrhagic events. There was an increased incidence of neutropenia (neutrophils <1·5×109/l) in the lefradafiban groups (5·2% vs 1·5% in the placebo group), which did not result from bone marrow depression but rather from a reversible redistribution of neutrophils by margination or clustering.Conclusion One month's treatment with the oral glycoprotein IIb/IIIa inhibitor lefradafiban in patients with unstable angina and myocardial infarction without persistent ST elevation resulted in a decrease in cardiac events with lefradafiban 30mg and a dose-dependent increase in haemorrhagic events. The observed favourable trend towards a reduction in cardiac events in patients with elevated troponin levels requires confirmation in a large clinical trial. [ABSTRACT FROM PUBLISHER]

Objectives Our objective was to investigate the actual incidence and clinical determinants of cough leading to discontinuation of ACE-inhibitors. Cough is the most frequent reason to stop ACE-inhibitor treatment. Methods We studied 27,492 ACE-inhibitor naïve patients randomized to the ACE-inhibitor perindopril or placebo using individual data of 3 clinical trials. Multivariate logistic regression analysis was used to study the incidence of cough in relation to baseline clinical characteristics including racial background. Results In 27,492 patients with cardiovascular disease, 1076 patients discontinued ACE-inhibitor perindopril due to cough (3.9%), 703 patients during run-in period of 4 weeks and 373 patients during a mean four years of follow-up. Significant determinants of cough were female gender (OR 1.92 95% CI 1.68-2.18), age above 65 years (OR 1.53 95% CI 1.35-1.73), and concomitant use of lipid-lowering agents (OR 1.37; 95% CI 1.18-1.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 4.4 (95% CI 3.1-5.4) in the subjects with highest score (i.e. all determinants present). Racial background was not related to a differential incidence of cough in patients of Caucasian or Asian descendent (OR 1.11 95% CI 0.92-1.39). Conclusion This large combined analysis of randomized clinical trials in 27,492 patients showed an overall lower incidence of cough leading to discontinuation of ACE-inhibitors (3.9%) as compared to literature. Clinical determinants of such cough are older age, female gender and concomitant use of lipid-lowering agents. In contrast, racial differences were not related to the incidence of cough. [ABSTRACT FROM AUTHOR]

Background: Although anxiety and depression have been associated with adverse outcomes in chronic heart failure (HF), data on temporal evolution of these symptoms are scarce. We aimed to investigate the association between repeatedly measured depression and anxiety symptoms and clinical outcome in chronic HF patients., Methods: In this prospective observational study, outpatients with chronic HF were included and followed-up for a maximum of 2.5 years. The hospital anxiety and depression scale (HADS) questionnaire was conducted every six months. The primary endpoint was a composite of HF hospitalization, cardiovascular death, heart transplantation and left ventricular assist device (LVAD) implantation. Cox and joint models were used to investigate the association between the HADS score and the endpoint., Results: A total of 362 patients filled out a median (25th-75th percentile) of 3 [2-4] questionnaires each. Mean ± SD age was 63 ± 13 years, 72% were men. Anxiety scores remained relatively stable leading up to the endpoint, while depression scores increased. Higher baseline depression scores were significantly associated with the endpoint (hazard ratio [HR] 1.68 and 95% confidence interval [CI] 1.19-2.36 per log(score+1), p = 0.003), while higher baseline anxiety scores did not reach statistical significance (HR [95% CI] 1.34 [0.99-1.83], p = 0.061). When repeatedly measured, both higher anxiety (HR [95% CI] 1.57[1.07-2.30], p = 0.022) and depression (HR [95% CI] 2.04 [1.39-3.06], p < 0.001) scores were significantly associated with the endpoint., Conclusion: Serial measurements of depression and anxiety symptoms identify chronic HF patients with increased risk of adverse clinical outcomes. Screening for both disorders should be considered in clinical practice., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into heart failure pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters as well as with elevated left atrial pressure (LAP), in patients with HFrEF, to provide insights into underlying mechanisms., Methods and Results: In 173 patients with HFrEF, we performed 6-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7 (inter-quartile range: 2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular [left ventricular ejection fraction (LVEF), global longitudinal strain (GLS)] and left atrial function [left atrial reservoir strain (LASr)] and elevated LAP (E/e' ratio >15) and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792, and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr, and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix. Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: cystatin-D, fibulin-5, and HSP40., Conclusion: Circulating proteins show varying associations with different echocardiographic parameters in patients with HFrEF. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct., Competing Interests: Conflict of interest: J.J.B. received independent research grant from Abbott for ISS and has had speaker engagement or advisory boards in the past 5 years with Astra Zeneca, Abbott, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Novartis, and Vifor. R.A.d.B. received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche and has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: We aimed to assess differences in clinical characteristics, prognosis, and the temporal evolution of circulating biomarkers in male and female patients with HFrEF., Methods: We included 250 patients (66 women) with chronic heart failure (CHF) between 2011 and 2013 and performed trimonthly blood sampling during a median follow-up of 2.2 years [median (IQR) of 8 (5-10) urine and 9 (5-10) plasma samples per patient]. After completion of follow-up we measured 8 biomarkers. The primary endpoint (PE) was the composite of cardiac death, cardiac transplantation, left ventricular assist device implantation, and hospitalization due to acute or worsened CHF. Joint models were used to determine whether there were differences in the temporal patterns of the biomarkers between men and women as the PE approached., Results: A total of 66 patients reached the PE of which 52 (78.8%) were male and 14 (21.2%) were female. The temporal patterns of all studied biomarkers were associated with the PE, and overall showed disadvantageous changes as the PE approached. For NT-proBNP, HsTnT, and CRP, women showed higher levels over the entire follow-up duration and concomitant numerically higher hazard ratios [NT-proBNP: women: HR(95%CI) 7.57 (3.17-21.93), men: HR(95%CI) 3.14 (2.09-4.79), p for interaction = 0.104, HsTnT: women: HR(95%CI) 6.38 (2.18-22.46), men: HR(95%CI) 4.91 (2.58-9.39), p for interaction = 0.704, CRP: women: HR(95%CI) 7.48 (3.43-19.53), men: HR(95%CI) 3.29 [2.27-5.44], p for interaction = 0.106). In contrast, temporal patterns of glomerular and tubular renal markers showed similar associations with the PE in men and women., Conclusion: Although interaction terms are not statistically significant, the associations of temporal patterns of NT-proBNP, HsTnT, and CRP appear more outspoken in women than in men with HFrEF, whereas associations seem similar for temporal patterns of creatinine, eGFR, Cystatin C, KIM-1 and NAG. Larger studies are needed to confirm these potential sex differences., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Hyperglycemia is associated with increased mortality in cardiac patients. However, the predictive value of admission- and average glucose levels in patients admitted to an intensive cardiac care unit (ICCU) has not been described., Methods: Observational study of patients admitted to the ICCU of a tertiary medical center in whom glucose levels were measured at and during admission. Over a 19-month period, 1713 patients were included. Mean age was 63±14 years, 1228 (72%) were male, 228 (17%) had known diabetes. Median (interquartile) glucose levels at admission were 7.9 (6.5-10.1) mmol/l; median glucose levels during ICCU admission (873 patients with three or more measurements) were 7.3 (6.7-8.3) mmol/l. Cox regression analysis was performed including the variables age, gender, admission diagnosis, length of stay, prior (cardio)vascular disease and diabetes., Results: A 1 mmol/l increase in admission glucose level (above 9 mmol/l) was associated with a 10% (95% confidence interval (CI): 7 -13%) increased risk for all-cause mortality. A 1 mmol/l higher average glucose level (above 8 mmol/l) was an additional independent predictor of mortality (HR 1.11, 95% CI: 1.03 - 1.20). At 30 days, 16.8% (97/579) of the patients with an admission glucose level in the highest tertile (>9.8 mmol/L) had died vs 5.2% (59/1134) of those with a lower admission glucose level., Conclusion: In a high risk ICCU population, both high admission glucose levels as well as high average glucose levels during hospitalization were independently associated with increased mortality, even when accounting for other risk factors and parameters of disease severity.

Congenital long QT-syndrome (LQTS) was diagnosed in three patients. The first patient, a 10-year-old girl, presented with recurrent episodes of syncope during swimming and was diagnosed with type 1 LQTS. The second patient, a 36-year-old asymptomatic man, was accidentally diagnosed with type 2 LQTS. His family history revealed syncope and sudden death at a young age after auditory stimuli. Type 3 LQTS was diagnosed post-mortem in a 16-year-old boy who died during his sleep. All clinical diagnoses were confirmed by genetic testing. Congenital LQTS is one of the leading causes of sudden cardiac death at a young age. Mutations in genes encoding for myocardial ion channel proteins lead to a prolonged QT-interval and abnormal ST-T segments in the 12-lead ECG. Patients may present with syncope or sudden cardiac death caused by ventricular tachyarrhythmias. Genotype-specific differences in ECG-abnormalities and triggers for cardiac events may help to distinguish the type of LQTS and make possible the initiation of genotype-specific treatment before the results of genetic testing are known. Identification of the genetic substrate by genetic testing, genotype-specific treatment, and the possibility of treatment with an implantable cardioverter-defibrillator have all led to dramatic improvement in the prognosis of patients with LQTS. Therefore, young patients with unexplained recurrent syncope after specific stimuli and those with atypical forms of epilepsy should be referred for cardiologic evaluation in a specialised centre.

Aim: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS)., Methods and Results: Peak CK-MB ratios (peak CK-MB level/upper limit of normal [ULN]) after PCI were analysed in 6164 patients with NSTE ACS from four randomized trials who underwent in-hospital PCI. We excluded 696 patients with elevated CK or CK-MB levels <24h before PCI; the primary analysis included 2384 of the remaining 5468 patients (43.6%) with CK-MB levels measured <==24h after PCI. The incidence of in-hospital heart failure (0.1%, 0.8%, 3.4%, 4.1%, and 6.1%; P<0.001), arrhythmias (0.8%, 1.9%, 6.9%, 4.1%, and 7.9%; P<0.001), cardiogenic shock (0.1%, 1.3%, 2.0%, 2.3%, and 2.6%; P=0.004), and mortality through 6 months (2.1%, 2.4%, 4.9%, 4.1%, and 5.7%, P=0.005) was increased with peak CK-MB ratios of 0-1, 1-3, 3-5, 5-10, and >10xULN, respectively. The continuous peak CK-MB ratio after PCI significantly predicted adjusted 6-month mortality (risk ratio, 1.06 per unit increase above ULN; 95% confidence interval, 1.01-1.11; P=0.017)., Conclusions: Greater CK-MB elevation after PCI is independently associated with adverse outcomes in NSTE ACS. These results underscore the adverse implications of elevated CK-MB levels after PCI in this high-risk population.

Background: Many patients with acute coronary syndromes are offered percutaneous coronary intervention. However, the appropriate indications for, and optimal timing of, such procedures are uncertain. We analysed timing of intervention and associated events (death and myocardial infarction) in the PURSUIT trial in which 9461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide, or placebo for 72 h. Other treatment was left to the investigators. 2430 patients underwent percutaneous coronary intervention within 30 days. Four groups were distinguished, who underwent percutaneous coronary intervention on day 1; on days 2 or 3; at 4 to 7 days; or between 8 until 30 days, for eptifibatide- and placebo-treated patients., Results: The four groups treated with placebo demonstrated total 30-day events of 15.9% for day 1 percutaneous coronary intervention, 17.7%, 15.0% and 18.2%, respectively, for successive intervals of later intervention. Later intervention was associated with more pre-procedural events (2.2% to 13.7%, P=0.001) which was balanced by a decrease in procedure-related events (12.1 to 3.1%, P=0.001), while the overall 30-day event rates were similar. Eptifibatide-treated patients with percutaneous coronary intervention on day 1 had the lowest rate of 30-day events (9.2%, P<0.05 vs other groups). In this group, pre-procedural risk was only 0.3%, while percutaneous coronary intervention on eptifibatide treatment was associated with low procedural risk (7.2%). The total 30-day event rate for later percutaneous coronary intervention in patients receiving eptifibatide was 14.0 on days 2 and 3, 15.0% for days 4 to 7 and 17.4% for days 7 to 30, respectively., Conclusion: Patients treated with a platelet glycoprotein IIb/IIIa receptor blocker, and early percutaneous coronary intervention (within 24 h) had the lowest event rate in this post hoc analysis. Thus 'watchful waiting' may not be the optimal strategy. Rather an early invasive strategy with percutaneous coronary intervention under protection of a platelet glycoprotein IIb/IIIa receptor blocker should be considered in selected patients. Randomized trials are warranted to verify this issue., (Copyright 2001 The European Society of Cardiology.)

Aims: Recurrent ischaemia, detected by continuous ECG monitoring, in patients with unstable angina increases the risk of unfavourable outcome. Studies that evaluated this relationship have been limited by the small series of patients. By combining data from three studies, the present analysis aims to provide an accurate assessment of the impact of recurrent ischaemia detected by multilead ECG-ischaemia monitoring on the occurrence of death and myocardial infarction in patients with acute coronary syndromes., Methods and Results: Data were obtained from CAPTURE, PURSUIT and FROST, three trials evaluating glycoprotein IIb/IIIa blockers in patients with non-ST-elevation acute coronary syndromes. Patients were monitored for 24 h after enrollment with a computer-assisted 12-lead or a vectorcardiographic ECG-ischaemia monitoring device. In a retrospective blinded analysis, recurrent ischaemic episodes were identified by a computer algorithm. The number of ischaemic episodes was normalized to 24 h. Ischaemic episodes were detected in 271 (27%) of 995 patients. There was a direct proportional relationship between the number of ischaemic episodes per 24 h and the probability of cardiac events at 5 and 30 days. The 30-day composite of death and myocardial infarction occurred in 5.7% of patients without episodes and increased to 19.7% in patients with >/=5 episodes. After adjustment for baseline predictors of adverse outcome, the relative risk of death or myocardial infarction at 5 and 30 days increased by 25% for each additional ischaemic episode per 24 h., Conclusions: This analysis emphasizes the need for integration of multilead ECG-ischaemia monitoring systems in coronary care units and emergency wards to improve early risk stratification in patients with acute coronary syndromes., (Copyright 2001 The European Society of Cardiology.)

Context: Abciximab, a potent inhibitor of the platelet glycoprotein IIb/IIIa receptor, reduces thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). Because of its potent inhibition of platelet aggregation, the effect of abciximab on risk of stroke is a concern., Objective: To determine whether abciximab use among patients undergoing PCI is associated with an increased risk of stroke., Design: Combined analysis of data from 4 double-blind, placebo-controlled, randomized trials (EPIC, CAPTURE, EPILOG, and EPISTENT) conducted between November 1991 and October 1997 at a total of 257 academic and community hospitals in the United States and Europe., Patients: A total of 8555 patients undergoing PCI with or without stent deployment for a variety of indications were randomly assigned to receive a bolus and infusion of abciximab (n = 5476) or matching placebo (n = 3079). One treatment group in EPIC received a bolus of abciximab only., Main Outcome Measure: Risk of hemorrhagic and nonhemorrhagic stroke within 30 days of treatment among abciximab and placebo groups., Results: No significant difference in stroke rate was observed between patients assigned abciximab (n = 22 [0.40%]) and those assigned placebo (n = 9 [0.29%]; P =.46). Excluding the EPIC abciximab bolus-only group, there were 9 strokes (0.30%) among 3023 patients who received placebo and 15 (0.32%) in 4680 patients treated with abciximab bolus plus infusion, a difference of 0.02% (95% confidence interval [CI], -0.23% to 0.28%). The rate of nonhemorrhagic stroke was 0.17% in patients treated with abciximab and 0.20% in patients treated with placebo (difference, -0.03%; 95% CI, -0.23% to 0.17%), and the rates of hemorrhagic stroke were 0.15% and 0.10%, respectively (difference, 0.05%; 95% CI, -0.11% to 0.21%). Among patients treated with abciximab, the rate of hemorrhagic stroke in patients receiving standard-dose heparin in EPIC, CAPTURE, and EPILOG was higher than in those receiving low-dose heparin in the EPILOG and EPISTENT trials (0.27% vs 0.04%; P =.057)., Conclusions: Abciximab in addition to aspirin and heparin does not increase the risk of stroke in patients undergoing PCI. Patients undergoing PCI and treated with abciximab should receive low-dose, weight-adjusted heparin.

Computer-assisted continuous monitoring of the ST-segment allows detection and quantification of recurrent ischemia in patients with acute coronary syndromes. In a substudy of the PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial, this technique was used to evaluate the effects of the glycoprotein IIb/IIIa inhibitor eptifibatide on the incidence and severity of recurrent ischemia, and to investigate the relationship between recurrent ischemia and the occurrence of subsequent death or myocardial (re)infarction. A total of 258 patients with unstable angina or evolving myocardial infarction without ST elevation were monitored for 24 hours during infusion with either eptifibatide or placebo with a computer-assisted 12-lead ECG-ischemia monitoring device. Recurrent ischemic episodes were identified by an automated computer algorithm. Two hundred and sixteen patients (84%) had ECG recordings suitable for analysis. Ischemic episodes were detected in 35 (33%) of the 105 eptifibatide patients and in 32 (29%) of the 111 placebo patients (not significant). No difference in ischemic burden was apparent between both treatment groups. Patients who exhibited 2 or more episodes of recurrent ischemia more frequently died or suffered a myocardial infarction, both at 7 and 30 days, as well as through the 6-month follow-up. A greater ischemic burden was significantly related to adverse outcome during the 6-month follow-up period. Real-time computer-assisted continuous multilead ECG-ischemia monitoring may help to identify patients with unstable coronary syndromes at increased risk of adverse outcome and, thus, allow for better prognostic triage and more appropriate selection of therapeutic strategies. Integration of these systems in coronary care units and emergency wards should, therefore, be recommended.

Aims: Variations in outcome of patients from different geographic regions have been observed in many large international trials. We analysed the factors that might contribute to the geographic variations in patient outcome and treatment effect as observed in the PURSUIT trial., Methods: In PURSUIT, 9461 patients with acute coronary syndromes without persistent ST-elevation were randomized to the platelet inhibitor eptifibatide or placebo for 72 h in 27 countries in four geographic regions: Western (n=3697) and Eastern Europe (n=1541) as well as North (n=3827) and Latin America (n=396). The primary end-point was the 30-day composite of death or myocardial infarction. In the initial univariate analysis, the treatment effect appeared greater in N. America than in W. Europe, while no benefit was apparent in L. America and E. Europe. However, the confidence intervals were wide and overlapping. To study these differences, a subdivision in an early and late patient outcome and treatment effect was made. Accordingly, we analysed the rate of death or infarction at 72 h censored for percutaneous coronary intervention and the rate between 3 and 30 days, respectively. Additional analyses were performed with different definitions of myocardial infarction using progressively higher thresholds of CK(-MB) elevation. Multivariable analysis was used to evaluate the relation between region and outcome and to determine the adjusted odds ratios for the eptifibatide treatment effect., Results: Major differences in baseline demographics were apparent among the four regions; in particular, more patients from E. Europe had characteristics associated with impaired outcome. Interventional treatment also varied considerably, with more patients from N. America undergoing revascularization. Despite differences in the 72 h event rate, eptifibatide showed a consistent trend towards a reduction in the composite end-point among all four regions and for all definitions of infarction. Relative reductions ranged from 17-42% in W. Europe, 23-35% in N. America, 0-33% in E. Europe, and 55-82% in L. America. After multivariable adjustment, the pattern of benefit with eptifibatide was consistent among the regions. In patients undergoing percutaneous coronary intervention during study drug infusion in W. Europe (n=266) and N. America (n=931), the relative reduction in myocardial infarction during medical therapy ranged from 56-75% in W. Europe and 14-67% in N. America, while the reduction in procedure-related events ranged from 12-44% and 25-61% for different definitions of infarction. After multivariable adjustment neither benefit nor rebound were apparent after study drug discontinuation, or after 3 days in all regions, except in L. America. In general, the differences in outcome and treatment effect were greatest when the protocol definition of myocardial infarction (CK(-MB) >1 upper normal limit) was applied. Under stricter definitions, these differences became smaller and disappeared with the investigator's assessment., Conclusion: The analysis suggests that the apparent differences in patient outcome and eptifibatide treatment effect can be explained largely by differences in baseline demographics and adjunctive treatment strategies as well as by the methodology of myocardial infarction definition and the adjudication process., (Copyright 2000 The European Society of Cardiology.)

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.

Objective: Comparison of diabetes regulation by strict or less strict observance of the relevant standard protocol of the Netherlands College of General Practitioners (NHG standard)., Setting: Two general practices in the region 'Nieuwe Waterweg Noord', near Rotterdam, the Netherlands., Design: Cross-sectional comparative descriptive study., Method: Type II diabetic patients from two general practices were investigated for diabetic symptoms, type of medication, metabolic abnormalities and (risk factors for) complications in relation to their HbA1c as a measure of mean blood glucose regulation. One GP strictly observed the NHG standard as a protocol, the other GP used it as a guideline., Results: Metabolic control was significantly better in the 'strictly observing' general practice than in the 'guideline' practice: HbA1c 7.3% (SD: 1.7) versus 8.1% (1.5) (p < 0.01). Systolic blood pressure was also significantly lower in the 'strict' practice: 141 mmHg (23) versus 155 mmHg (21) (p < 0.01), but mean age was lower and mean duration of diabetes was significantly shorter. The prevalence of macrovascular complications, diabetic retinopathy and nephropathy did not differ significantly in these practices; symptoms of polyneuropathy, however, were found more often in the patients of the 'strict' practice (41% versus 20%; p < 0.05)., Conclusion: Good metabolic control in patients with type II diabetes mellitus is made possible by strict application of the NHG standard for general practitioners.