Stefan James

ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation

ACEn: angiotensin-converting enzymenACSn: acute coronary syndromenADPn: adenosine diphosphatenAFn: atrial fibrillationnAMIn: acute myocardial infarctionnAVn: atrioventricularnAIDA-4n: Abciximab Intracoronary vs. intravenously Drug ApplicationnAPACHE IIn: Acute Physiology Aand Chronic

Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis.

Background— Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention. Methods and Result— Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR,1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76). Conclusion— In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00391872.

Troponin T levels and risk of 30-day outcomes in patients with the acute coronary syndrome: prospective verification in the GUSTO IV trial

BACKGROUND: A third-generation troponin T assay with improved precision and a lower detection limit has been developed. However, the appropriate cutoff for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality has not been established. METHODS: A retrospective evaluation of data from the Fragmin and fast Revascularization during InStability in Coronary artery disease II (FRISC-II) trial suggested that a cutoff below 0.1 microg/L for troponin T levels might be more useful in risk stratification. A prospective validation of two cutoff levels (0.03 microg/L and 0.01 microg/L) was performed in 7115 patients with non-ST-elevation acute coronary syndrome from the Global Utilization of Strategies To open Occluded arteries IV (GUSTO-IV) trial. RESULTS: Patients with troponin T levels >0.1 microg/L had greater 30-day mortality (5.5% [201/3679]) than did those with levels <or=0.1 microg/L (2.2% [75/3436], P <0.001). A cutoff value of 0.03 microg/L provided better discrimination between high and low risk: 5.1% (234/4552) versus 1.6% (42/2563). However, a cutoff value at the lower limit of detection, 0.01 microg/L, provided the best discrimination: 5.0% (254/5123) versus 1.1% (22/1992) (P<0.001). This cutoff level had the highest negative predictive value; it also discriminated best for the combined endpoint of death and myocardial infarction. CONCLUSION: Using a cutoff of <or=0.01 microg/L for the third-generation troponin T assay, the detection level of the assay, is useful for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality.

Transcatheter Implantation of the MONARC Coronary Sinus Device for Mitral Regurgitation 1-Year Results From the EVOLUTION Phase I Study (Clinical Evaluation of the Edwards Lifesciences Percutaneous Mitral Annuloplasty System for The Treatment of Mitral Regurgitation)

OBJECTIVESnThis study sought to assess the safety and efficacy of transcatheter valve annuloplasty in patients with mitral regurgitation (MR).nnnBACKGROUNDnMitral regurgitation is associated with a worsened prognosis in patients with dilated cardiomyopathy. Surgical mitral annuloplasty reduces the septal-lateral dimension of the mitral annulus resulting in improved leaflet coaptation with a reduction in regurgitation. Percutaneous annuloplasty with the MONARC device (Edwards Lifesciences, Irvine, California) implanted within the coronary sinus is designed to reduce mitral regurgitation through a similar mechanism.nnnMETHODSnA total of 72 patients with MR grade ≥ 2 were enrolled at 8 participating centers in 4 countries. Clinical evaluation and transthoracic echocardiography were performed at baseline and at 3, 6, and 12 months. Multislice cardiac computed tomography and coronary angiography were performed at baseline and 3 months.nnnRESULTSnThe MONARC device was implanted in 59 of 72 patients (82%). The primary safety end point (freedom from death, tamponade, or myocardial infarction at 30 days) was met in 91% of patients at 30 days and in 82% at 1 year. Computed tomography imaging documented passage of the great cardiac vein over an obtuse marginal artery in 55% of patients and was associated with angiographic coronary artery compression in 15 patients and myocardial infarction in 2 patients (3.4%). At 12 months, a reduction in MR by ≥ 1 grade was observed in 50.0% of 22 implanted patients with matched echocardiograms and in 85.7% of 7 patients with baseline MR grade ≥ 3.nnnCONCLUSIONSnImplantation of the MONARC device in the coronary sinus is feasible and may reduce MR. However, coronary artery compression may occur in patients in whom the great cardiac vein passes over a coronary artery, necessitating strategies in future studies to avoid this occurrence.

Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes A Substudy From the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial

Background—Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (≥75 years of age) with acute coronary syndrome compared with those <75 years of age. Methods and Results—The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years of age (n=2878) and those <75 years of age (n=15 744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged ≥75 years (hazard ratio, 1.02; 95% confidence interval, 0.82–1.27) or patients aged <75 years (hazard ratio, 1.04; 95% confidence interval, 0.94–1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction. Conclusions—The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Long-Term Results After Simple Versus Complex Stenting of Coronary Artery Bifurcation Lesions Nordic Bifurcation Study 5-Year Follow-Up Results

OBJECTIVESnThis study sought to report the 5-year follow-up results of the Nordic Bifurcation Study.nnnBACKGROUNDnRandomized clinical trials with short-term follow-up have indicated that coronary bifurcation lesions may be optimally treated using the optional side branch stenting strategy.nnnMETHODSnA total of 413 patients with a coronary bifurcation lesion were randomly assigned to a simple stenting strategy of main vessel (MV) and optional stenting of side branch (SB) or to a complex stenting strategy, namely, stenting of both MV and SB.nnnRESULTSnFive-year clinical follow-up data were available for 404 (98%) patients. The combined safety and efficacy endpoint of cardiac death, non-procedure-related myocardial infarction, and target vessel revascularization were seen in 15.8% in the optional SB stenting group as compared to 21.8% in the MV and SB stenting group (pxa0= 0.15). All-cause death was seen in 5.9% versus 10.4% (pxa0= 0.16) and non-procedure-related myocardial infarction in 4% versus 7.9% (pxa0=xa00.09) in the optional SB stenting group versus the MV and SB stenting group, respectively. The rates of target vessel revascularization were 13.4% versus 18.3% (pxa0= 0.14) and the rates of definite stent thrombosis were 3% versus 1.5% (pxa0= 0.31) in the optional SB stenting group versus the MV and SB stenting group, respectively.nnnCONCLUSIONSnAt 5-year follow-up in the Nordic Bifurcation Study, the clinical outcomes after simple optional side branch stenting remained at least equal to the more complex strategy of planned stenting of both the main vessel and the side branch.

Differences in Restenosis Rate With Different Drug-Eluting Stents in Patients With and Without Diabetes Mellitus: A Report From the SCAAR (Swedish Angiography and Angioplasty Registry)

OBJECTIVESnOur aim was to evaluate restenosis rate of drug-eluting stents (DES) in patients with and without diabetes mellitus (DM) in a real-world setting.nnnBACKGROUNDnDES seem less effective in patients with DM.nnnMETHODSnThe SCAAR (Swedish Coronary Angiography and Angioplasty Registry) includes all patients undergoing percutaneous coronary intervention in Sweden. From April 1, 2004, to April 20, 2008, all restenoses detected at a subsequent angiography and all DES types implanted at more than 500 occasions were assessed using Cox regression.nnnRESULTSnFour DES types qualified for inclusion. In total, 35,478 DES were implanted at 22,962 procedures in 19,004 patients and 1,807 restenoses were reported over a mean 29 months follow-up. In the entire population, the restenosis rate per stent was 3.5% after 1 year and 4.9% after 2 years. The adjusted risk of restenosis was higher in patients with DM compared with that in patients without DM (relative risk [RR]: 1.23, 95% confidence interval [CI]: 1.10 to 1.37). In patients with DM, restenosis was twice as frequent with the zotarolimus-eluting Endeavor stent (Medtronic, Minneapolis, Minnesota) compared with that in the other DES types. The Endeavor stent and the sirolimus-eluting Cypher stent (Cordis, Johnson & Johnson, Miami, Florida) had higher restenosis rates in patients with DM compared with those in patients without DM (RR: 1.77, 95% CI: 1.29 to 2.43 and RR: 1.25, 95% CI: 1.04 to 1.51). Restenosis rate with the paclitaxel-eluting Taxus Express and Liberté (Boston Scientific, Natick, Massachusetts) stents was unrelated to DM. Mortality did not differ between different DES.nnnCONCLUSIONSnRestenosis rate with DES was higher in patients with DM compared with that in patients without DM. There seem to be important differences between different brands of DES.

Unfractionated heparin administration in patients treated with bivalirudin during primary percutaneous coronary intervention is associated lower mortality and target lesion thrombosis: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

Background Bivalirudin reduces bleeding events and is associated with a lower mortality than the combination of unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitor during primary percutaneous coronary intervention (PCI). However, the effect of adding UFH in patients with ST elevation myocardial infarction (STEMI) treated with bivalirudin during primary PCI is unknown. Methods Patients enrolled in the national Swedish Coronary Angiography and Angioplasty Registry who underwent primary PCI due to STEMI with bivalirudin as anticoagulant were evaluated. Patients were divided into two groups: those treated with bivalirudin only and those treated with bivalirudin plus a bolus dose of UFH. Results 2996 patients were included in the study: 1928 (64%) received only bivalirudin and 1068 (36%) received bivalirudin plus a bolus dose of UFH. The primary combined endpoint of death or target lesion thrombosis at 30u2005days occurred more often in the bivalirudin group (11.3% vs 6.5%, OR 0.55, 95% CI 0.41 to 0.72, p<0.001). This difference remained significant after adjustment (HR 0.64, 95% CI 0.44 to 0.95, p=0.03). Death at 30u2005days and definite target lesion thrombosis at 30u2005days did not differ between the two groups after adjustment (9.2% vs 5.1%, adjusted HR 0.66, 95% CI 0.42 to 1.03, p=0.07 and 2.3% vs 1.5%, adjusted HR 0.59, 95% CI 0.27 to 1.33, p=0.21, respectively). Conclusion An additional bolus dose of UFH is associated with a lower rate of death or definite target lesion thrombosis at 30u2005days in patients undergoing primary PCI with bivalirudin as anticoagulant.

Prevalence and clinical outcomes of undiagnosed diabetes mellitus and prediabetes among patients with high-risk non–ST-segment elevation acute coronary syndrome

BACKGROUNDnWe examined the prevalence of undiagnosed diabetes or prediabetes and associations with ischemic outcomes among non-ST-segment elevation acute coronary syndrome (ACS) patients.nnnMETHODSnWe categorized 8795 EARLY ACS trial patients into one of the following groups: known diabetes (n = 2860 [32.5%]; reported on the case report form), undiagnosed diabetes (n = 1069 [12.2%]; no diabetes history and fasting glucose ≥126 mg/dL or hemoglobin A1c ≥6.5%), prediabetes (n = 947 [10.8%]; fasting glucose ≥110 to <126 mg/dL, or normal (n = 3919 [44.5%]). Adjusted associations of known diabetes, undiagnosed diabetes, and prediabetes (versus normal) with 30-day and 1-year outcomes were determined.nnnRESULTSnUndiagnosed diabetes was associated with greater 30-day death or myocardial infarction (MI) (ORadj 1.28, 95% CI 1.05-1.57), driven primarily by greater 30-day mortality (ORadj 1.65, 95% CI 1.09-2.48). Known diabetic patients had 30-day death or MI outcomes similar to those of normal patients, but 30-day mortality was higher (ORadj 1.40, 95% CI 1.01-1.93). Prediabetic patients had 30-day death or MI outcomes similar to those of normal patients. One-year mortality was greater among known diabetic patients (HRadj 1.38, 95% CI 1.13-1.67) but not among those with undiagnosed diabetes or prediabetes.nnnCONCLUSIONSnUndiagnosed diabetes and prediabetes were common among high-risk non-ST-segment elevation ACS patients. Routine screening for undiagnosed diabetes may be useful since these patients seem to have worse short-term outcomes and deserve consideration of alternative management strategies.

Reduction in First and Recurrent Cardiovascular Events With Ticagrelor Compared With Clopidogrel in the PLATO Study

Background— We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (eg, cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events. Methods and Results— In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model, and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary end point events versus 1225 for patients on clopidogrel (rate ratio, 0.86; 95% confidence interval, 0.79–0.93; P=0.003). The number of additional events was numerically lower for ticagrelor (189 versus 205; P=0.40), resulting in a hazard for time to second event/death of 0.80 (95% confidence interval, 0.70–0.90; P<0.001) and a number needed to treat of 54. For cardiovascular death/myocardial infarction/stroke/(severe) recurrent ischemia/transient ischemic attack/arterial thrombotic events, total events were fewer with ticagrelor (2030 versus 2290; rate ratio, 0.88; 95% confidence interval, 0.82–0.95; P<0.001), with fewer recurrent events with ticagrelor (740 versus 834; P=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% confidence interval, 0.75–0.91; P<0.001). Recurrent PLATO major or Thrombolysis in Myocardial Infarction (TIMI) major non–coronary artery bypass graft bleeding events were infrequent and not different between the two therapies (P=0.96 and 0.38, respectively). Conclusions— In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared with clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported. Clinical Trial Registration— URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00391872.