Birgit Vogel

Influence of updated guidelines on short- and long-term mortality in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS)

AIM In 2002 the ACC/AHA guidelines for the management of patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) were updated. We aimed to answer whether the implementation of updated guidelines was capable of influencing short- and long-term mortality in these patients. METHODS We analyzed data on 812 consecutive patients who were admitted with either UA or NSTEMI between 2001 and 2004. Patients admitted in the two years before the implementation of updated guidelines (UA(01/02) group and NSTEMI(01/02) group) were compared to patients admitted in the two years thereafter (UA(03/04) group and NSTEMI(03/04) group). Yearly follow-up concerning all-cause mortality was obtained up to four years. RESULTS The rate of revascularizations, the percentage of procedures performed within 48 h of admission, and the administration of clopidogrel increased significantly. However, still many - especially high-risk - patients did not receive revascularization. Patients of both UA groups had an identical in-hospital mortality rate. Differences in mortality between groups gained statistical significance over time (four-year mortality; 15.1% for the UA(03/04) group vs. 26.5% for the UA(01/02) group, p=0.014; HR 0.49 95% CI 0.28-0.87). In patients with NSTEMI in-hospital mortality decreased from 18.4% in the NSTEMI(01/02) group to 9.6% in the NSTEMI(03/04) group (p=0.011; HR 0.47 95% CI 0.26-0.84), and 1-year mortality from 34.7% to 25.1% (p=0.038; HR 0.63 95% CI 0.41-0.98), respectively. Mortality rates beyond one year were still lower in the NSTEMI(03/04) group as compared to the NSTEMI(01/02) group but it did not reach statistical significance. Multivariate Cox-regression analysis revealed furthermore that also patients with higher age and/or renal dysfunction benefit from an early invasive strategy. CONCLUSION The implementation of updated guidelines for NSTE-ACS had significant impact on short- and long-term mortality. However, an early invasive strategy is still withheld to a significant number of high-risk patients, who would benefit from an invasive treatment.

Sex-related differences in baseline characteristics, management and outcome in patients with acute coronary syndrome without ST-segment elevation.

Aim: To detect sex-related differences in baseline characteristics, management and outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: Data from 812 consecutive patients admitted to our cardiology department for NSTE-ACS between 2001 and 2004 were obtained. Early invasive therapy was defined as revascularization during first hospital stay. A seven-year follow-up for the clinical endpoint of all-cause mortality could be obtained in 342 women and 440 men, respectively. Results: Compared with men, women were significantly older and more likely to suffer from renal insufficiency. The proportion treated with clopidogrel at admission was 43.6% for women and 52.7% for men, respectively (p=0.011). Significantly fewer women underwent an early invasive therapy compared with men (27.5% vs. 35.2%; p=0.021). Age and renal insufficiency were the strongest predictors for a conservative approach in both female and male patients. After adjustment for baseline characteristics there was no significant difference in treatment between women and men (odds ratio 0.89; 95% confidence interval 0.59–1.35; p=0.588). While in-hospital mortality was similar between the sexes, long-term mortality was significantly higher in women compared with men (8.2% vs. 7.0%; p=0.549 for in-hospital mortality and 54.8% vs. 39.3%; p<0.001 for seven-year mortality). However, after adjustment for baseline characteristics and treatment there was no significant difference in long-term mortality between women and men (hazard ratio 1.14; 95% confidence interval 0.89–1.47; p=0.307). Conclusion: In these patients with NSTE-ACS women were less likely to undergo an early invasive therapy compared with men due to their higher age and the higher rate of renal insufficiency. After adjustment for age, comorbidities and treatment female sex was not associated with worse long-term outcome.

Variability of on-treatment platelet reactivity in patients on clopidogrel

Abstract Response to clopidogrel therapy is subject to inter-individual variability. However, data with regard to on-treatment platelet reactivity over time in patients undergoing coronary stenting are scarce. For this prospective observational study, 102 consecutive patients on dual antiplatelet therapy undergoing coronary stenting due to stable coronary artery disease (CAD; n = 29), non ST-elevation acute coronary syndrome (NSTE-ACS; n = 45) and ST-elevation myocardial infarction (STEMI; n = 28) were enrolled. Vasodilator-stimulated phosphoprotein-phosphorylation assay was performed at baseline, as well as 1, 3 and 6 months thereafter. Platelet reactivity index (PRI) measured after 1, 3 and 6 months was lower compared to baseline values (p < 0.001). Variables responsible for reduced response to clopidogrel at baseline (reticulated platelet fraction, simvastatin therapy) and during steady-state phase (body mass index, blood glucose concentrations, cholesterol/HDL-ratio and quality of life score) were different. High on-treatment platelet reactivity (HTPR)-phenotype (cut-off = 50% PRI) within the first month changed in 31% of stable CAD, 33% of NSTE-ACS and 39% of STEMI patients, respectively. HTPR-phenotype in the steady-state phase (month 1 to 6) changed in 45% of stable CAD, 33% of NSTE-ACS and 25% of STEMI patients. Response to clopidogrel and accordingly platelet function might vary over time, especially when a cut-off based approach, is used. There was a significant reduction of on-treatment platelet reactivity within the first month after percutaneous coronary intervention with stenting which was maintained for up to 6 months. Variables associated with reduced response to clopidogrel at baseline and during steady-state phase were different, as the latter mainly reflected an unfavorable metabolic profile, comprising elevated BMI, blood glucose levels as well as cholesterol/HDL-ratio.

Patterns and associations between DAPT cessation and 2-year clinical outcomes in left main/proximal LAD versus other PCI: Results from the Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients (PARIS) registry

OBJECTIVES Percutaneous coronary intervention (PCI) of the left main (LM) or proximal left anterior descending artery (pLAD) is considered high-risk as these segments subtend substantial left ventricular myocardial area. We assessed the patterns and associations between dual antiplatelet therapy (DAPT) cessation and 2-year outcomes in LM/pLAD vs. other PCI from the all-comer PARIS registry. METHODS Two-year major adverse cardiovascular events (MACE) were a composite of cardiac death, myocardial infarction, definite/probable stent thrombosis or target lesion revascularization. DAPT cessation was predefined as physician-guided permanent discontinuation, temporary interruption, or non-recommended disruption due to non-compliance or bleeding. RESULTS Of the study population (n=5018), 25.0% (n=1252) underwent LM/pLAD PCI and 75.0% (n=3766) PCI to other segments. Compared to others, LM/pLAD patients presented with fewer comorbidities, less frequent acute coronary syndromes but more multivessel and bifurcation disease treated with greater stent lengths. Two-year adjusted risk of MACE (11.4% vs. 11.6%; HR 1.10, 95% CI 0.90-1.34, p=0.36) was similar between LM/pLAD vs. other patients. DAPT discontinuation was significantly higher (43.3% vs. 39.4%, p=0.01) in LM/pLAD patients with borderline significance for lower disruption (10.0% vs. 14.7%, p=0.059) compared to other patients. DAPT discontinuation was not associated with higher risk of MACE in LM/pLAD (HR 0.65, 95% CI 0.34-1.25) or other PCI groups (HR 0.67, 95% CI 0.47-0.95). CONCLUSIONS LM/pLAD PCI was not an independent predictor of 2-year MACE. Compared to other PCI, patients undergoing LM/pLAD PCI had higher rates of physician recommended DAPT discontinuation, however, discontinuation did not result in greater adverse events.

Contrast induced acute kidney injury in acute coronary syndrome patients: A single centre experience

Background: The aim of the study was to investigate predictors of contrast induced acute kidney injury, in-hospital and long-term mortality in patients with acute coronary syndrome treated by percutaneous coronary intervention. Methods: We investigated 536 consecutive patients with acute coronary syndrome who underwent percutaneous coronary intervention. Contrast induced acute kidney injury was classified according to risk, injury, failure, loss of kidney function and end-stage kidney disease/acute kidney injury network (RIFLE/AKIN) criteria into those with normal kidney function, risk, RIFLE stage I and those with stage ⩾II. We investigated in-hospital, all-cause mortality during index hospitalization and long-term all-cause mortality during the follow-up period of 94 months (interquartile 81.6–108.9 months) in adjustment with parameters of the Global Risk of Acute Coronary Events score. Results: Patients with contrast induced acute kidney injury had worse baseline clinical characteristics and displayed more co-morbidities than patients with normal kidney function. In multivariate logistic regression analysis intra-aortic balloon pump use, congestive heart failure, age >75 years and admission serum creatinine >1.5mg/dl were independent predictors of contrast induced acute kidney injury development. contrast induced acute kidney injury RIFLE stage ⩾II was an independent predictor of in-hospital mortality (odds ratio 33.16, confidence interval 1.426–770.79, p=0.029) and long-term mortality (hazard ratio 4.713, confidence interval 1.53–14.51, p=0.007) even after adjustment for confounders (variables of Global Risk of Acute Coronary Events score). Conclusion: Contrast induced acute kidney injury is a common complication of acute coronary syndrome patients treated by percutaneous coronary intervention. Advanced deterioration in renal function after percutaneous coronary intervention is an independent predictor for in-hospital and long-term mortality.

Admission Proinsulin Is Associated with Mortality in Patients with Admission Hyperglycemia during Acute Coronary Syndrome: Results from a Pilot Observational Study

BACKGROUND Acute hyperglycemia (AHG) is associated with mortality in patients with acute coronary syndrome (ACS). The extent to which hyperproinsulinemia contributes to worse clinical outcomes for this specific patient population is unknown. METHODS We included 308 consecutive ACS patients who underwent coronary angioplasty in this pilot observational study. Patients were separated into 3 groups: patients with proven diabetes mellitus (DM group) (n =55), nondiabetic patients with a normal glucose concentration at admission (NAG group) (n =175), and nondiabetic patients with AHG at presentation (AHG group) (n =78). Blood samples for glucose, insulin, and proinsulin measurements were obtained at admission. The primary end point of the study was all-cause mortality, which was assessed at a mean follow-up of 19 months (interquartile range, 12-28 months). RESULTS Patients in the AHG and DM groups had significantly (P =0.048) higher all-cause mortality compared with the NAG group. A univariate Cox regression analysis revealed that the proinsulin concentration was significantly associated with all-cause mortality for all study participants (hazard ratio, 1.013; 95% CI, 1.002-1.024; P =0.023). AHG patients with increased proinsulin concentrations showed a mortality rate similar to that of DM patients but had a significantly higher mortality rate than patients with AHG and a low proinsulin concentration (χ² =7.57; P =0.006) and patients with NAG (with or without increased proinsulin) [χ² =7.66 (P =0.006) and 13.98 (P < 0.001), respectively]. A multivariate regression analysis revealed that the concentrations of glucose and proinsulin at admission were significant (P =0.002) predictors of all-cause mortality. CONCLUSIONS An increased proinsulin concentration may be a marker for mortality in ACS patients with hyperglycemia at admission and without known diabetes. Further studies are needed to evaluate the role of metabolic parameters such as proinsulin.

Reperfusion strategies in acute myocardial infarction and multivessel disease

Approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel disease. The optimal reperfusion strategy in these patients is still uncertain. Whether percutaneous coronary intervention (PCI) of only the culprit vessel or a strategy of complete revascularization, either in a simultaneous or staged multivessel PCI approach, should be performed remains unclear. Although a large number of observational studies have mostly shown worse clinical outcomes associated with a multivessel PCI approach, increasing evidence from randomized controlled trials suggests that multivessel PCI is safe, while reducing the need for revascularization in selected patients, compared with culprit vessel-only PCI. However, adequately-powered studies are still needed to determine the best treatment strategy in patients with STEMI and multivessel disease, particularly to demonstrate a reduction in the hard end point of death or myocardial infarction. In this Review, we provide a comprehensive summary of current evidence on the different treatment options for patients with STEMI and multivessel disease, highlighting current guideline recommendations and providing future directions on reperfusion strategies in these patients.

Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical outcomes following transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial

Prior studies have suggested that patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk for adverse cardiovascular events. Whether procedural bivalirudin compared with unfractionated heparin (UFH) has a beneficial effect on early outcomes in these patients is unknown. We examined for the effect of baseline or new‐onset AF within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by AF status, on 30‐day outcomes from the BRAVO 3 trial.

Antiplatelet treatments: recent evidence from randomized controlled trials

Purpose of review To provide an overview of selected randomized studies reported over the last 2 years evaluating antiplatelet therapies in patients with either acute or stable manifestations of atherosclerosis. Recent findings From large outcome trials included evidence for reduced risk of ischemic events associated with use of ticagrelor and aspirin versus aspirin alone, albeit with an increased bleeding risk in patients with stable coronary artery disease and history of myocardial infarction. No benefit regarding ischemic outcomes could be demonstrated for ticagrelor monotherapy compared with aspirin or clopidogrel in patients with stroke or peripheral vascular disease, respectively. Results from pharmacokinetic/pharmacodynamic studies suggest that switching from prasugrel to ticagrelor is safe, regardless of the use of a loading dose, and that loading with prasugrel or ticagrelor compared with clopidogrel leads to more prompt and potent platelet inhibition in patients undergoing ad hoc percoutaneous coronary intervention. No evidence could be demonstrated for the prognostic value of routine platelet function monitoring to adjust antiplatelet therapy. Summary Large outcome trials demonstrated various effects of antithrombotic strategies including ticagrelor on clinical outcomes across patient populations. Pharmacokinetic/pharmacodynamic studies confirmed a more prompt and potent platelet inhibition after loading with the new P2Y12 inhibitors versus clopidogrel, and suggested the safety of switching from prasugrel to ticagrelor.

Effect of valve design and anticoagulation strategy on 30-day clinical outcomes in transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial

Selection of valve type and procedural anticoagulant may impact bleeding and vascular complications in transfemoral transcatheter aortic valve replacement (TAVR). We sought to compare outcomes by valve [balloon expandable (BE) or non‐BE] and anticoagulant [bivalirudin vs. unfractionated heparin (UFH)] type from the BRAVO‐3 trial.