Thomas Kellerth

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial

BACKGROUND Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease. METHODS In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651. FINDINGS Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke. INTERPRETATION The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease. FUNDING Biosensors, Aarhus University Hospital, and participating sites.

Randomized Comparison of Final Kissing Balloon Dilatation Versus No Final Kissing Balloon Dilatation in Patients With Coronary Bifurcation Lesions Treated With Main Vessel Stenting The Nordic-Baltic Bifurcation Study III

Background— It is unknown whether the preferred 1-stent bifurcation stenting approach with stenting of the main vessel (MV) and optional side branch stenting using drug-eluting stents should be finalized by a kissing balloon dilatation (FKBD). Therefore, we compared strategies of MV stenting with and without FKBD. Methods and Results— We randomized 477 patients with a bifurcation lesion to FKBD (n=238) or no FKBD (n=239) after MV stenting. The primary end point was major adverse cardiac events: cardiac death, non–procedure-related index lesion myocardial infarction, target lesion revascularization, or stent thrombosis within 6 months. The 6-month major adverse cardiac event rates were 2.1% and 2.5% (P=1.00) in the FKBD and no-FKBD groups, respectively. Procedure and fluoroscopy times were longer and more contrast media was needed in the FKBD group than in the no-FKBD group. Three hundred twenty-six patients had a quantitative coronary assessment. At 8 months, the rate of binary (re)stenosis in the entire bifurcation lesion (MV and side branch) was 11.0% versus 17.3% (P=0.11), in the MV was 3.1% versus 2.5% (P=0.68), and in the side branch was 7.9% versus 15.4% (P=0.039) in the FKBD versus no-FKBD groups, respectively. In patients with true bifurcation lesions, the side branch restenosis rate was 7.6% versus 20.0% (P=0.024) in the FKBD and no-FKBD groups, respectively. Conclusions— MV stenting strategies with and without FKBD were associated with similar clinical outcomes. FKBD reduced angiographic side branch (re)stenosis, especially in patients with true bifurcation lesions. The simple no-FKBD procedures resulted in reduced use of contrast media and shorter procedure and fluoroscopy times. Long-term data on stent thrombosis are needed. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00914199.

Oxygen Therapy in Suspected Acute Myocardial Infarction

BACKGROUND The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS In this registry‐based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient‐air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient‐air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1‐year all‐cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X‐AMI ClinicalTrials.gov number, NCT01787110.)

The Effect of Music Intervention in Relation to Gender During Coronary Angiographic Procedures: A Randomized Clinical Trial:

Several studies have evaluated music interventions prior and after coronary angiography and percutaneous coronary intervention (PCI), but there is no clear evidence showing that music has an effect on patients during these procedures. The purpose was to investigate the effects of music on anxiety, angina, pain, relaxation, and comfort in patients during angiographic procedures and to evaluate gender differences. The study was a four-armed, prospective randomized controlled trial included 240 patients undergoing coronary angiography and/or PCI. Patients were allocated to receive relaxing music, MusiCure® or standard care during the procedure. Outcome measures were; puncture pain and the discomfort related to it, angina and the discomfort related to it, anxiety, experience of the sound environment, discomfort of lying still, and the doses of anxiolytics and analgesics during the procedure. No differences were found between the music and control groups regarding any of the trial endpoints or gender-related differences. The overall rating of the sound environment and feeling of relaxation was high. In conclusion, music intervention in patients undergoing angiographic procedures was highly feasible, but not effective in this study though the delivery of music went smoothly and did not disturb the examination and patients and staff alike looked favorably on it.

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction

BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial‐artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS In this multicenter, randomized, registry‐based, open‐label clinical trial, we enrolled patients with either ST‐segment elevation myocardial infarction (STEMI) or non‐STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial‐artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow‐up. RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end‐point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart–Lung Foundation and others; VALIDATE‐SWEDEHEART ClinicalTrialsRegister.eu number, 2012–005260–10; ClinicalTrials.gov number, NCT02311231.)

Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS).

BACKGROUND This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial. METHODS 124 patients with definite ST were assessed by IVUS during the acute ST event. The study was conducted in 15 high-volume percutaneous coronary intervention -centers in the Nordic-Baltic countries. RESULTS In early or late ST there were no differences in ISA between DES and BMS. In very late ST, ISA was a more frequent finding in DES than in BMS (52% vs.16%; p=0.005) and the maximum ISA area was larger in DES compared to BMS (1.1 ± 2.3mm(2) vs. 0.1 ± 0.5mm(2); p=0.004). Further, ISA was more prevalent in sirolimus-eluting than in paclitaxel-eluting stents (58% vs. 37%; p=0.02). Stent fractures were found both in DES (16%) and BMS (24%); p=0.28, and not related to time of stent thrombosis occurrence. For stents with nominal diameters ≥ 2.75 mm, 38% of the DES and 22% of the BMS had a minimum stent area of less than 5mm(2); p=0.14. CONCLUSIONS Very late stent thrombosis was more prevalent and associated with more extensive ISA in DES than in BMS treated patients. Stent fracture was a common finding in ST after DES and BMS implantation.

Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments : experiences from the SWEDEHEART registry 1995-2014

Abstract Aims Impact of changes of treatments on outcomes in ST-elevation myocardial infarction (STEMI) patients in real-life health care has not been documented. Methods and results All STEMI cases (n = 105.674) registered in the nation-wide SWEDEHEART registry between 1995 and 2014 were included and followed for fatal and non-fatal outcomes for up to 20 years. Most changes in treatment and outcomes occurred from 1994 to 2008. Evidence-based treatments increased: reperfusion from 66.2 to 81.7%; primary percutaneous coronary intervention: 4.5 to 78.0%; dual antiplatelet therapy from 0 to 89.6%; statin: 14.1 to 93.6%; beta-blocker: 78.2 to 91.0%, and angiotensin-converting-enzyme/angiotensin-2-receptor inhibitors: 40.8 to 85.2% (P-value for-trend <0.001 for all). One-year mortality decreased from 22.1 to 14.1%. Standardized incidence ratio compared with the general population decreased from 5.54 to 3.74 (P < 0.001). Cardiovascular (CV) death decreased from 20.1 to 11.1%, myocardial infarction (MI) from 11.5 to 5.8%; stroke from 2.9 to 2.1%; heart failure from 7.1 to 6.2%. After standardization for differences in demography and baseline characteristics, the change of 1-year CV-death or MI corresponded to a linear trend of 0.915 (95% confidence interval: 0.906–0.923) per 2-year period which no longer was significant, 0.997 (0.984–1.009), after adjustment for changes in treatment. The changes in treatment and outcomes were most pronounced from 1994 to 2008. Conclusion Gradual implementation of new and established evidence-based treatments in STEMI patients during the last 20 years has been associated with prolonged survival and lower risk of recurrent ischaemic events, although a plateauing is seen since around 2008.

Long-Term Outcome of Incomplete Revascularization After Percutaneous Coronary Intervention in SCAAR (Swedish Coronary Angiography and Angioplasty Registry)

OBJECTIVES The aim of this study was to describe current practice regarding completeness of revascularization in patients with multivessel disease undergoing percutaneous coronary intervention (PCI) and to investigate the association of incomplete revascularization (IR) with death, repeat revascularization, and myocardial infarction (MI) in a large nationwide registry. BACKGROUND The benefits of multivessel PCI are controversial. METHODS Between 2006 and 2010 we identified 23,342 patients with multivessel disease in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and merged data with official Swedish health data registries. IR was defined as any nontreated significant (60%) stenosis in a coronary artery supplying >10% of the myocardium. RESULTS Patients with IR (n = 15,165) were older, had more extensive coronary disease, and more often had ST-segment elevation MI at presentation than those with complete revascularization (CR) (n = 8,177). All-cause 1-year mortality, MI, and repeat revascularization were higher in IR than CR: 7.1% versus 3.8%, 10.4% versus 6.0%, and 20.5% versus 8.5%, respectively. Propensity score methodology was used in the adjusted analyses. Adjusted hazard ratio (HR) for the composite of death, MI, or repeat revascularization at 1 year was higher in IR than CR: 2.12 (95% confidence interval [CI]: 1.98 to 2.28; p < 0.0001). Adjusted HR for death and the combination of death/MI were 1.29 (95% CI: 1.12 to 1.49; p = 0.0005) and 1.42 (95% CI: 1.30 to 1.56; p < 0.0001), respectively. CONCLUSIONS Incomplete revascularization at the time of hospital discharge in patients with multivessel disease undergoing PCI is associated with a high risk of recurrent 1-year adverse cardiac events.

Aspects on the intensity and the relief of pain in the prehospital phase of acute coronary syndrome: experiences from a randomized clinical trial

The primary aim of this study was to evaluate the pain relief and tolerability of two pain-relieving strategies in the prehospital phase of presumed acute coronary syndrome (ACS), and the secondary aim was to assess the relationship between the intensity and relief of pain and heart rate, blood pressure, and ST deviation. Patients with chest pain judged as caused by ACS were randomized (open) to either metoprolol 5 mg intravenously (i.v.) three times at 2-min intervals (n = 84; metoprolol group) or morphine 5 mg i.v. followed by metoprolol 5 mg three times i.v (n = 80; morphine group). Pain was assessed on a 10-grade scale before randomization and 10, 20, and 30 min thereafter. The mean pain score decreased from 6.5 at randomization to 2.8 30 min later, with no significant difference between groups. The percentages with complete pain relief (pain score ≤1) after 10, 20, and 30 min were 11, 16, and 21%, respectively, with no difference between groups. Hypotension was less frequent in the metoprolol group compared with the morphine group (0 vs. 6.3%; P=0.03), as was nausea/vomiting (7.2 vs. 24.0%; P=0.004). At randomization intensity of pain was associated with degree of ST elevation (P=0.009). The degree of pain relief over 30 min was associated with decrease in heart rate (P=0.03) and decrease in ST elevation (P=0.01).In conclusion, in the prehospital phase of presumed ACS, neither a pain-relieving strategy including an anti-ischemic agent alone nor an analgesic plus anti-ischemic strategy in combination resulted in complete pain relief. Fewer side effects were found with the former strategy. Other pain-relieving strategies need to be evaluated.

Oxygen therapy in ST-elevation myocardial infarction

Aims To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes. Methods and results The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days. Conclusions Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.