http://repub.eur.nl/res/aut/10617/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/34172/ 2011-09-01T00:00:00Z Objective: To investigate the combined beneficial effect of statin and beta-blocker use on perioperative mortality and myocardial infarction (MI) in patients undergoing abdominal aortic aneurysm surgery (AAA). Background: Patients undergoing elective AAA-surgery identified by clinical risk factors and dobutamine stress echocardiography (DSE) as being at high-risk often have considerable cardiac complication rate despite the use of beta-blockers. Methods: We studied 570 patients (mean age 69 ±9 years, 486 males) who underwent AAA-surgery between 1991 and 2001 at the Erasmus MC. Patients were evaluated for clinical risk factors (age>70 years, histories of MI, angina, diabetes mellitus, stroke, renal failure, heart failure and pulmonary disease), DSE, statin and beta-blocker use. The main outcome was a composite of perioperative mortality and MI within 30 days of surgery. Results: Perioperative mortality or MI occurred in 51 (8.9%) patients. The incidence of the composite endpoint was significantly lower in statin users compared to nonusers (3.7% vs. 11.0%; crude odds ratio (OR): 0.31, 95% confidence interval (CI): 0.13-0.74; p = 0.01). After correcting for other covariates, the association between statin use and reduced incidence of the composite endpoint remained unchanged (OR: 0.24,95% CI: 0.10-0.70; p = 0.01). Beta-blocker use was also associated with a significant reduction in the composite endpoint (OR: 0.24, 95% CI: 0.11-0.54). Patients using a combination of statins and beta-blockers appeared to be at lower risk for the composite endpoint across multiple cardiac risk strata; particularly patients with 3 or more risk factors experienced significantly lower perioperative events. Conclusions: A combination of statin and beta-blocker use in patients with AAA-surgery is associated with a reduced incidence of perioperative mortality and nonfatal MI particularly in patients at the highest risk. http://repub.eur.nl/res/pub/33503/ 2011-03-03T00:00:00Z Background: Meta-analyses of randomized trials show that primary percutaneous coronary intervention (PPCI) results in lower mortality than fibrinolytic therapy in patients with myocardial infarction. We investigated which categories of patients with myocardial infarction would benefit most from the strategy of PPCI and, thus, have lowest numbers needed to treat to prevent a death. Methods: Individual patient data were obtained from 22 (n = 6,763) randomized trials evaluating efficacy and safety of PPCI versus fibrinolysis. A risk score was developed and validated to estimate the probability of 30-day death in individuals. Patients were then divided in quartiles according to risk. Subsequent analyses were performed to evaluate if the treatment effect was modified by estimated risk. Results: Overall, 446 patients (6.6%) died within 30 days after randomization. The mortality risk score contained clinical characteristics, including the time from symptom onset to randomization. The c-index was 0.76, and the Hosmer-Lemeshow test was nonsignificant, reflecting adequate discrimination and calibration. Patients randomized to PPCI had lower mortality than did patients randomized to fibrinolysis (5.3% vs 7.9%, adjusted odds ratio 0.63, 95% CI 0.42-0.84, P < .001). The interaction between risk score and allocated treatment interaction term had no significant contribution (P = .52) to the model, indicating that the relative mortality reduction by PPCI was similar at all levels of estimated risk. In contrast, the absolute risk reduction was strongly related to estimated risk at baseline: the numbers needed to treat to prevent a death by PPCI versus fibrinolysis was 516 in the lowest quartile of estimated risk compared with only 17 in the highest quartile. Conclusion: Primary percutaneous coronary intervention is consistently associated with a strong relative reduction in 30-day mortality, irrespective of patient baseline risk, and should therefore be considered as the first choice reperfusion strategy whenever feasible. If access to percutaneous coronary intervention is >2 hours, fibrinolysis remains a legitimate option in low-risk patients because of the small absolute risk reduction by PPCI in this particular cohort. http://repub.eur.nl/res/pub/28704/ 2010-03-01T00:00:00Z Objectives: The aim of this study was to obtain a valid estimate of the clinical effects of primary percutaneous coronary intervention (PPCI) in relation to age. Background: Treatment with PPCI is most beneficial in high-risk myocardial infarction patients. Paradoxically, elderly patients, who are at increased risk of adverse outcome, are often withheld PPCI. Methods: Individual patient data were obtained from 22 randomized trials (n = 6,763) evaluating the clinical effects of PPCI versus fibrinolysis (FL). Differences in 30-day death, repeat myocardial infarction, and stroke between patients randomized to FL and PPCI were determined in 5 age-strata: ≤50, >50 to 60, >60 to 70, >70 to 80, and >80 years. Treatment effects are reported as odds ratios (ORs) and 95% confidence intervals (CI). Multivariable logistic regression analyses, which included age × treatment interaction, were applied to examine evidence of heterogeneity in age-specific ORs. Results: Thirty-day death increased with increasing age and ranged from 1.1% (FL) and 1.8% (PPCI) in patients ≤50 years to 26.4% and 18.3% in patients >80 years of age. The point estimate of treatment effect (overall adjusted OR: 0.65; 95% CI: 0.52 to 0.79) was compatible with a mortality reduction favoring PPCI in all age-strata (except in patients ≤50 years of age), and 95% CIs were largely overlapping. There was no evidence of heterogeneity in ORs between age categories. Similar results were observed for repeat myocardial infarction and stroke. Conclusions: In this analysis of randomized trials, the reduction in clinical end points by PPCI was not influenced by age. Hence, age per se should not be considered an exclusion criterion for the application of PPCI. http://repub.eur.nl/res/pub/11676/ 2008-03-14T00:00:00Z Objective: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. Methods: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60–69, 70–79, >=80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). Results: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5–4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients >=80 years had half of the NNT and a third of the NNH of patients <60 years. Conclusions: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted. http://repub.eur.nl/res/pub/10567/ 2007-10-17T00:00:00Z Risk, the possibility of loss or injury, is indeed a fixture in all aspects of our lives, from investing in the stock market to crossing the street. This concept that we now take for granted is in fact relatively novel. Some have argued that the ability to describe, estimate and control risk is a key distinction between past and modern times.1 In early civilization, the future of human beings was largely thought to be at the whim of the gods. The turning point came during the Renaissance when Chevalier de Méré, a French nobleman with an affinity for gambling and mathematics, challenged the famed French mathematician Blaise Pascal to solve an infamous puzzle: How to divide the stakes of an unfinished game of chance between two players when one of them is ahead.1,2 Collaboration between Pascal and Pierre de Fermat, a lawyer and a talented mathematician, resulted in a solution and consequently, the theory of probability was born. And it is this concept that is at the heart of modern cardiovascular medicine and research. http://repub.eur.nl/res/pub/35306/ 2007-08-01T00:00:00Z Background: Although relationships between chronic Chlamydia pneumoniae (Cpn) infection and the risk of coronary events in stable coronary artery disease patients have been reported, a similar link in acute coronary syndrome (ACS) patients has not been consistently observed. Methods: In a nested case-control substudy of the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial, 295 cases (30-day death/myocardial infarction [MI]) were matched by age, sex, baseline creatine kinase-myocardial kinase, and smoking status with 295 control subjects. To test the hypothesis on 1-year mortality, another subset (n = 276) was drawn from the 590-patient cohort; 138 patients who died at 1 year plus the matching controls who survived at 1 year. We measured Cpn IgG and IgA antibody titers in baseline serum with microimmunofluorescence. Conditional logistic regression was used to quantify the prognostic relevance seropositivity (IgG ≥1:32; IgA ≥1:16) and elevated titer levels. Results: The prevalence of Cpn IgG and IgA was similar between cases and controls (30-day death/MI: IgG, 80% vs 85%, P = .126; IgA, 45% vs 37%, P = .079), and were not statistically significant predictors of 30-day death/MI after baseline adjustment. Likewise, the 1-year death cohort had comparable proportions of Cpn IgG and IgA among cases and controls (86% vs 91% [P = .265] and 49% vs 43% [P = .334], respectively), and did not add prognostic value. Conclusions: These findings are in concert with study results suggesting that chronic Cpn infection is not associated with 30-day death/MI or 1-year mortality in non-ST elevation ACS. http://repub.eur.nl/res/pub/35314/ 2007-07-09T00:00:00Z Background: There is growing evidence for a clinical benefit of primary percutaneous coronary intervention (PCI) compared with fibrinolysis; however, whether the treatment effect is consistent among patients with diabetes mellitus is unclear. We compared PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction in patients with diabetes mellitus. Methods: A pooled analysis of individual patient data from 19 trials comparing primary PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction was performed. Trials that enrolled at least 50 patients with ST-segment elevation myocardial infarction and randomized patients to receive either primary PCI or fibrinolysis were considered for inclusion in our study. Clinical end points were total deaths, recurrent infarction, death or nonfatal recurrent infarction, and stroke, measured 30 days after randomization. Results: Of 6315 patients, 877 (14%) had diabetes. Thirty-day mortality (9.4% vs 5.9%; P<.001) was higher in patients with diabetes. Mortality was lower after primary PCI compared with fibrinolysis in both patients with diabetes (unadjusted odds ratio, 0.49; 95% confidence interval, 0.31-0.79; P=.004) and without diabetes (unadjusted odds ratio, 0.69; 95% confidence interval, 0.54-0.86, P=.001), with no evidence of heterogeneity of treatment effect (P=.24 for interaction). Recurrent infarction and stroke were also reduced after primary PCI in both patient groups. After multivariable analysis, primary PCI was associated with decreased 30-day mortality in patients with and without diabetes, with a point estimate of greater benefit in diabetic patients. Conclusions: Diabetic patients with ST-segment elevation myocardial infarction treated with reperfusion therapy have increased mortality compared with patients without diabetes. The beneficial effects of primary PCI compared with fibrinolysis in diabetic patients are consistent with effects in nondiabetic patients. http://repub.eur.nl/res/pub/8380/ 2005-01-01T00:00:00Z STUDY OBJECTIVE: International variation in the outcomes of patients with acute coronary syndromes (ACS) has been well reported. The relative contributions of patient, hospital, and country level factors on clinical outcomes, however, remain unclear, and thus, was the objective of this study. DESIGN: Multilevel logistic regression models were developed for death/(re)infarction (MI) at 30 days and death in one year, with patients (1st level) nested in hospitals (2nd level) and hospitals in countries (3rd level).Settings: The GUSTO IV ACS clinical trial was carried out at 458 hospital sites in 24 countries. PATIENTS: 7800 non-ST segment elevation (NSTE) ACS patients. MAIN RESULTS: There were substantial variations among countries in the processes and outcomes of care at 30 days, ranging from 5.4% to 50.0% for percutaneous coronary intervention, 4.3% to 21.2% for coronary artery bypass graft surgery, 5.0% to 13.9% for 30 day death/(re)MI, and 4.9% to 14.8% for one year mortality. However, the residual inter-country variations in 30 day death/(re)MI and one year mortality became non-significant and nearly disappeared (p > 0.500 for both) after adjusting for key baseline patient characteristics and hospital factors, which became significant (p < 0.01 for both). Patient level factors accounted for 96%-99% of total variation in these end points, leaving the remaining 1% and 4% of variance attributable to hospital level factors. CONCLUSION: The international differences in clinical outcomes in this study of NSTE ACS are primarily accounted for by the patient level factors, with hospital level factors playing a minor part, and the country level factors a negligible one. These findings have significant policy and research implications involving international collaboration and comparisons. http://repub.eur.nl/res/pub/13153/ 2003-04-15T00:00:00Z BACKGROUND: Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. METHODS AND RESULTS: To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%; P<0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. CONCLUSIONS: This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.