Magnus Ohman

Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction: The Joint European Society of Cardiology/ American College of Cardiology Committee∗

This document was developed by a consensus conference initiated by Kristian Thygesen, MD, and Joseph S. Alpert, MD, after formal approval by Lars Rydén, MD, President of the European Society of Cardiology (ESC), and Arthur Garson, MD, President of the American College of Cardiology (ACC). All of the participants were selected for their expertise in the field they represented, with approximately one-half of the participants selected from each organization. Participants were instructed to review the scientific evidence in their area of expertise and to attend the consensus conference with prepared remarks. The first draft of the document was prepared during the consensus conference itself. Sources of funding appear in Appendix A. The recommendations made in this document represent the attitudes and opinions of the participants at the time of the conference, and these recommendations were revised subsequently. The conclusions reached will undoubtedly need to be revised as new scientific evidence becomes available. This document has been reviewed by members of the ESC Committee for Scientific and Clinical Initiatives and by members of the Board of the ESC who approved the document on April 15, 2000.*

A Risk Score to Predict Bleeding in Patients With Acute Coronary Syndromes

OBJECTIVES The aim of this study was to develop a practical risk score to predict the risk and implications of major bleeding in acute coronary syndromes (ACS). BACKGROUND Hemorrhagic complications have been strongly linked with subsequent mortality in patients with ACS. METHODS A total of 17,421 patients with ACS (including non-ST-segment elevation myocardial infarction [MI], ST-segment elevation MI, and biomarker negative ACS) were studied in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) and the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trials. An integer risk score for major bleeding within 30 days was developed from a multivariable logistic regression model. RESULTS Non-coronary artery bypass graft surgery (CABG)-related major bleeding within 30 days occurred in 744 patients (7.3%) and had 6 independent baseline predictors (female sex, advanced age, elevated serum creatinine and white blood cell count, anemia, non-ST-segment elevation MI, or ST-segment elevation MI) and 1 treatment-related variable (use of heparin + a glycoprotein IIb/IIIa inhibitor rather than bivalirudin alone) (model c-statistic = 0.74). The integer risk score differentiated patients with a 30-day rate of non-CABG-related major bleeding ranging from 1% to over 40%. In a time-updated covariate-adjusted Cox proportional hazards regression model, major bleeding was an independent predictor of a 3.2-fold increase in mortality. The link to mortality risk was strongest for non-CABG-related Thrombolysis In Myocardial Infarction (TIMI)-defined major bleeding followed by non-TIMI major bleeding with or without blood transfusions, whereas isolated large hematomas and CABG-related bleeding were not significantly associated with subsequent mortality. CONCLUSIONS Patients with ACS have marked variation in their risk of major bleeding. A simple risk score based on 6 baseline measures plus anticoagulation regimen identifies patients at increased risk for non-CABG-related bleeding and subsequent 1-year mortality, for whom appropriate treatment strategies can be implemented.

A Prospective, Randomized Clinical Trial of Hemodynamic Support With Impella 2.5 Versus Intra-Aortic Balloon Pump in Patients Undergoing High-Risk Percutaneous Coronary Intervention The PROTECT II Study

Background— Although coronary artery bypass grafting is generally preferred in symptomatic patients with severe, complex multivessel, or left main disease, some patients present with clinical features that make coronary artery bypass grafting clinically unattractive. Percutaneous coronary intervention with hemodynamic support may be feasible for these patients. Currently, there is no systematic comparative evaluation of hemodynamic support devices for this indication. Methods and Results— We randomly assigned 452 symptomatic patients with complex 3-vessel disease or unprotected left main coronary artery disease and severely depressed left ventricular function to intra-aortic balloon pump (IABP) (n=226) or Impella 2.5 (n=226) support during nonemergent high-risk percutaneous coronary intervention. The primary end point was the 30-day incidence of major adverse events. A 90-day follow-up was required, as well, by protocol. Impella 2.5 provided superior hemodynamic support in comparison with IABP, with maximal decrease in cardiac power output from baseline of −0.04±0.24 W in comparison with −0.14±0.27 W for IABP (P=0.001). The primary end point (30-day major adverse events) was not statistically different between groups: 35.1% for Impella 2.5 versus 40.1% for IABP, P=0.227 in the intent-to-treat population and 34.3% versus 42.2%, P=0.092 in the per protocol population. At 90 days, a strong trend toward decreased major adverse events was observed in Impella 2.5–supported patients in comparison with IABP: 40.6% versus 49.3%, P=0.066 in the intent-to-treat population and 40.0% versus 51.0%, P=0.023 in the per protocol population, respectively. Conclusions— The 30-day incidence of major adverse events was not different for patients with IABP or Impella 2.5 hemodynamic support. However, trends for improved outcomes were observed for Impella 2.5–supported patients at 90 days. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00562016.

Flow Cytometric Monitoring of Glycoprotein IIb/IIIa Blockade and Platelet Function in Patients With Acute Myocardial Infarction Receiving Reteplase, Abciximab, and Ticlopidine Continuous Platelet Inhibition by the Combination of Abciximab and Ticlopidine

BackgroundImprovement of thrombolysis may be achieved by concomitant strong platelet inhibition. To monitor platelet function in patients with myocardial infarction (n=46) who were treated with the fibrinolytic agent reteplase, the glycoprotein (GP) IIb/IIIa blocker abciximab, and the ADP receptor antagonist ticlopidine, we developed a flow cytometric assay. Methods and ResultsBinding of abciximab to platelets was directly monitored as the percentage of platelets stained by a goat anti-mouse antibody. Blood drawn 10 minutes and 2 hours after the start of therapy with reteplase and abciximab and during the 12-hour infusion of abciximab demonstrated a maximal blockade of GP IIb/IIIa (10 minutes, 86.2±10.3%; 12 hours, 85.8±7.1%). Starting at 24 hours, abciximab binding gradually decreased (24 hours, 74.6±16.2%; 48 hours, 66.8±14.9%; 72 hours, 60.5±16.7%; 96 hours, 49.4±17.8%; 120 hours, 35.8±16.4%; and 144 hours, 29.9±15.3%). Binding of a chicken anti-fibrinogen antibody to platelets, indicating the level of functional blockade of GP IIb/IIIa, was inversely correlated with the binding of abciximab (r =−0.72, P <0.0001). In blood drawn at 10 minutes, platelet aggregation was maximally inhibited but recovered within 48 hours even if the majority of GP IIb/IIIa receptors were still blocked by abciximab. Reteplase did not influence abciximab binding and did not activate platelets, as measured by P-selectin expression, fibrinogen binding, and platelet aggregation. Platelet inhibition that was achieved during the first 24 hours by abciximab was directly maintained by additional treatment with ticlopidine. ConclusionsFlow cytometric monitoring of platelet function allows differentiation of the effects of reteplase, abciximab, and ticlopidine. The combination of abciximab and ticlopidine is an attractive therapeutic strategy that provides a fast and continuous platelet inhibition.

Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: Results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry

BACKGROUND Current American College of Cardiology/American Heart Association guidelines recommend initiation or intensification of statin therapy to achieve low-density lipoprotein cholesterol (LDL-C) goals after an acute coronary syndrome (ACS), yet little is known about the actual practice of intensifying lipid-lowering (LL) therapy and LDL-C achievement from hospital admission to 1-year follow-up. METHODS The MAINTAIN registry enrolled ACS patients from January 2006 through September 2007, collecting data on statin formulation, dose, and lipid profiles at both baseline and 12 months. Statin intensity (estimated LDL-C lowering) was categorized by formulation and dose as either moderate (<40%) or intensive (≥40%). In-hospital LL intensification is described and LDL goal attainment is reported for patients with complete baseline and 12-month lipid panels. RESULTS Of the 788 patients without contraindications to LL, 40% were on LL therapy before admission, and 89% at discharge. Among patients on LL therapy with LDL-C>100 mg/dL at admission, only 37% (n=38) had their LL therapy intensified. Among 382 patients with 12 months of data, 89% (n=341) were discharged on a statin. Of these, 89% were still on a statin at 12-month follow-up. A LDL-C goal of ≤100 mg/dL was achieved in 71% of patients, but the optional LDL-C goal≤70 mg/dL was achieved in only 31%. CONCLUSIONS Most high-risk ACS patients are prescribed statin therapy at hospital discharge and remain on therapy at 12-month follow-up. Despite this, the LDL-C goal of ≤70 mg/dL is achieved in a small minority. There is substantial opportunity to intensify LL therapy after ACS to achieve guideline LDL-C goals and prevent future morbidity and mortality.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high vascular risk

Objective ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely prescribed in patients with high cardiovascular (CV) risk. However, whether both classes have equivalent effectiveness to prevent CV events remains unclear. The aim of this study was to compare the incidence of major CV events between ACEI and ARB users. Methods The Reduction of Atherothrombosis for Continued Health registry is an observational study who enrolled 69 055 individuals with high CV risk. Among them, 40 625 patients (ACEIs 67.9% and ARBs 32.1%) were included. Main outcome was rates of CV mortality, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for CV disease at 4 years. Results In a propensity score-adjusted cohort, the incidence of the primary outcome was lower in patients on ARBs compared with ACEIs (29.2% vs 33.4%; adjusted HR 0.90; 95% CI 0.86 to 0.95; p<0.001). Similar results were observed for CV (6.9% vs 8.2%; HR 0.83; 95% CI 0.75 to 0.93; p=0.001) and all-cause mortality (11.6% vs 12.6%; HR 0.89; 95% CI 0.82 to 0.97; p=0.005). Analyses using propensity score matching yielded similar results. History of diabetes or estimated glomerular filtration rate did not affect the results. ARB use was associated with lower rates of all-cause mortality in secondary prevention but not in primary prevention patients (p-value for interaction=0.03). Conclusion ARB use appears to be associated with 10% lower rates of CV events compared with ACEIs, especially in patients with established CV disease. Our results suggest that ARBs may provide superior protection against CV events than ACEIs in high-risk patients in real-world practice.

Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction: The Joint European Society of Cardiology/ American College of Cardiology Committee∗∗A list of contributors to this ESC/ACC Consensus Document is provided in Appendix B.

This document was developed by a consensus conference initiated by Kristian Thygesen, MD, and Joseph S. Alpert, MD, after formal approval by Lars Rydén, MD, President of the European Society of Cardiology (ESC), and Arthur Garson, MD, President of the American College of Cardiology (ACC). All of the participants were selected for their expertise in the field they represented, with approximately one-half of the participants selected from each organization. Participants were instructed to review the scientific evidence in their area of expertise and to attend the consensus conference with prepared remarks. The first draft of the document was prepared during the consensus conference itself. Sources of funding appear in Appendix A. The recommendations made in this document represent the attitudes and opinions of the participants at the time of the conference, and these recommendations were revised subsequently. The conclusions reached will undoubtedly need to be revised as new scientific evidence becomes available. This document has been reviewed by members of the ESC Committee for Scientific and Clinical Initiatives and by members of the Board of the ESC who approved the document on April 15, 2000.*

HIGH-RISK PERCUTANEOUS CORONARY INTERVENTION RESULTS IN SUBSTANTIAL REVERSE REMODELING OF THE LEFT VENTRICLE IN ISCHEMIC CARDIOMYOPATHY

Reverse left ventricular (LV) remodeling is associated with decreased clinical events. The PROTECT II study was a multicenter trial of high-risk percutaneous coronary intervention (PCI) with hemodynamic support randomized to Impella 2.5 or intra-aortic balloon pump (IABP) in patients with ischemic

014 Risk score to predict serious bleeding in stable outpatients with atherothrombosis

Context Assessment of bleeding risk is often crucial for making decisions regarding chronic use of antithrombotics. Objective To develop a risk score to quantify bleeding risk in outpatients. Design, Setting, and Participants We studied patients enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) Registry, a cohort of 68 236 patients with or at risk of atherothrombosis. The outcome of interest was serious bleeding (non-fatal hemorrhagic stroke or bleeding requiring hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed. Competing scores were compared on their discriminative ability via logistic regression. The score was validated externally using the CHARISMA population. Results From a final cohort of 56 616 patients, 804 (1.42%) experienced serious bleeding between baseline and 2 years. A nine-item bleeding risk score, ranging from 0 to 23 points, was constructed including age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, and hypercholesterolemia. Observed incidence of bleeding at 2 years was: 0.46% in patients with a score ≤6; 0.95% for scores 7-8; 1.25% for scores 9-10; and 2.76% for scores ≥11. The scores discriminative performance was consistent in CHARISMA and REACH (c-statistics 0.63 and 0.68, respectively); calibration in the CHARISMA population was very good (modified Hosmer-Lemeshow χ2=4.74; P=.69). Conclusions Bleeding risk increases dramatically with a score >10. This score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients with atherothrombosis.

Low-osmolar ionic contrast media was better than nonionic media for ischemic complications of angioplasty

Source Citation Grines CL, Schreiber TL, Savas V, et al. A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable angina undergoing ...