Complete revascularization with multivessel PCI for myocardial infarction

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS: We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS: At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P=0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P=0.62 and P=0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS: Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.). (AU)

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

BackgroundTwo large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice.MethodsThe trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear...

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial

Background Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reducesvascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronaryangiography with possible intervention.Methods The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group,multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voiceresponse system to radial or femoral artery access. The primary outcome was a composite of death, myocardialinfarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. Findings Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries.3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72–1·17; p=0·50). Of the six prespecifi ed subgroups, there was a signifi cant interaction for the primary outcome with benefi t for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28–0·87; p=0·015)...

Design and rationale of the radIal Vs. femorAL access for coronary intervention (RIVAL) trial: A randomized comparison of radial versus femoral access for coronary angiography or intervention in patients with acute coronary syndromes

Background Major bleeding in acute coronary syndromes (ACS) is associated with an increased risk of subsequentmortality and recurrent ischemic events. Observational data and small randomized trials suggest that radial instead of femoralaccess for coronary angiography/intervention results in fewer bleeding complications, with preserved and possibly improvedefficacy. Radial access versus femoral access has yet to be formally evaluated in a randomized trial adequately powered forthe comparison of clinically important outcomes.Objectives The aim of this study is to evaluate the efficacy and safety of radial versus femoral access for coronaryangiography/intervention in patients with ACS managed with an invasive strategy.Design This was a multicenter international randomized trial with blinded assessment of outcomes. 7021 patients withACS (with or without ST elevation) have been randomized to either radial or femoral access for coronary angiography/intervention. The primary outcome is the composite of death, myocardial infarction, stroke, or non–coronary artery bypassgraft-related major bleeding up to day 30. The key secondary outcomes are (1) death, myocardial infarction, or stroke up today 30 and (2) non–coronary artery bypass graft-related major bleeding up to day 30. Percutaneous coronary intervention(PCI) success rates will also be compared between the two access sites.Conclusions The RIVAL trial will help define the optimal access site for coronary angiography/intervention in patientswith ACS.

Early versus delayed invasive intervention in acute coronary syndromes

Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain.Methods We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography ¡Ü24 hours after randomization)or delayed intervention (coronary angiography ¡Ý36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, orrefractory ischemia at 6 months.Results Coronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6%of patients in the early-intervention group, as compared with 11.3% in the delayedintervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P = 0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group(12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P = 0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P = 0.01 for heterogeneity)...

Glucose levels compared with diabetes history in the risk assessment of patients with acute myocardial infarction

Background Both a history of diabetes mellitus and elevated inhospital glucose levels predict death after acute myocardial infarction (AMI). However, only diabetes history (and not glucose levels) is routinely considered in AMI risk assessment. Methods We conducted a post hoc analysis of 2 randomized controlled trials of AMI with ST-segment elevation to compare the prognostic value of inhospital glucose levels with diabetes history in 30,536 subjects. Average inhospital glucose (mean of glucose levels at admission, 6 hours, and 24 hours), diabetes history, and death at 30 days (occurring in 2,808subjects) were documented. Results Average glucose predicted 30-day death (OR 1.10 per 1-mmol/L [18-mg/dL] increase, 95% CI 1.09-1.11, P < .0001); this was unchanged after adjusting for diabetes history. In contrast, diabetes history alone predicted 30-day death (OR 1.63, 95% CI 1.48-1.78, P < .0001), but not after adjusting for average glucose (OR 0.98, 95% CI 0.88-1.09, P = .72). The C-indices (areas under the receiver operating characteristic curves) for 30-day death were 0.54 for diabetes history alone, 0.64 for average glucose alone, and 0.64 for glucose plus diabetes. Higher glucose levels predicted death in patients with and without diabetes history, but this relationship was more steep in nondiabetic subjects such that their rate of 30-day death (13.2%) matched that of diabetic patients (13.7%) when average glucose was ¡Ý144 mg/dL (8 mmol/L) (P = .55 after multivariable adjustment). Conclusions Although diabetes history is routinely considered in the risk stratification of AMI patients, inhospital glucose levels are a much stronger predictor of death and should be incorporated in their risk assessment. Patients with AMI with inhospitalglucose ¡Ý144 mg/dL have a very high risk of death regardless of diabetes history.

Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study

In the setting of percutaneous coronary intervention (PCI), due to a paucity of data, the optimal dose of aspirin isuncertain. We evaluated the safety of different doses of aspirin after PCI.Methods and results In the PCI-CURE study, 2658 patients with acute coronary syndromes undergoing PCI were stratified into three aspirin dose groups 200 mg (high, n » 1064), 101–199 mg (moderate, n » 538), and 100 mg (low, n » 1056). For efficacy, the moderate- (7.4%) and high-dose groups (8.6%) had similar rates of cardiovascular death, myocardialinfarction, or stroke compared with the low-dose group (7.1%). For safety, major bleeding was increased with highdose aspirin [3.9, 1.5, and 1.9% in the high-, moderate-, and low-dose groups; hazard ratio (HR) of high vs. low dose 2.05 (95% CI 1.20–3.50, P » 0.009]. The net adverse clinical events (death, MI, stroke, major bleeding) favoured low-over high-dose aspirin (8.4 vs. 11.0%, HR 1.31, 95% CI 1.00–1.73 P » 0.056). Conclusion In this large observational analysis of patients undergoing PCI, low-dose aspirin appeared to be as effective as higherdoses in preventing ischaemic events but was also associated with a lower rate of major bleeding and an improved net efficacy to safety balance.

Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction.

CONTEXT: The clinical benefit of glucose-insulin-potassium (GIK) infusion in patients with ST-segment elevation myocardial infarction (STEMI) is unclear. While some smaller trials suggest benefit, in the CREATE-ECLA trial, GIK infusion had no effect on 30-day mortality in 20,201 patients. OBJECTIVES: To determine the association between GIK infusion therapy and 30-day and 6-month outcomes in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Primary analysis of the OASIS-6 GIK randomized controlled trial of 2748 patients with acute STEMI; prespecified analyses of the combined trial data from the OASIS-6 GIK and CREATE-ECLA GIK trial populations of 22,943 patients with acute STEMI; subgroup analysis on the timing of initiation of GIK infusion therapy and outcomes; and post hoc analyses exploring whether GIK infusion may cause early harm by increasing glucose and potassium levels and net fluid gain. INTERVENTION: High-dose GIK solution consisting of 25% glucose, 50 U/L of regular insulin, and 80 mEq/L of potassium infused at 1.5 mL/kg per hour for 24 hours. MAIN OUTCOME MEASURES: Mortality rates at 30 days and 6 months in the OASIS-6 GIK trial and rates of death, heart failure, and the composite of death or heart failure at 3 and 30 days in the combined OASIS-6 GIK and CREATE-ECLA GIK trial populations. RESULTS: At 6 months, 148 (10.8%) GIK infusion patients and 143 (10.4%) control patients died in the OASIS-6 trial (hazard ratio [HR], 1.04; 95% CI, 0.83-1.31; P = .72); 153 (11.1%) GIK patients and 185 (13.5%) control patients had heart failure (HR, 0.83; 95% CI, 0.67-1.02; P = .08); and 240 (17.5%) GIK patients and 264 (19.2%) control patients had a composite of death or heart failure (HR, 0.91; 95% CI, 0.76-1.08; P = .27). In the prespecified analyses of the combined trial data, there were 712 deaths (6.2%) in the GIK group and 632 deaths (5.5%) in the control group at 3 days (HR, 1.13; 95% CI, 1.02-1.26; P = .03). This difference disappeared by 30 days, with 1108 deaths (9.7%) in the GIK group and 1068 (9.3%) in the control group (HR, 1.04; 95% CI, 0.96-1.13; P = .33). GIK therapy increased levels of glucose, potassium, and net fluid gain postinfusion, all 3 of which predicted death after adjusting for multiple confounders. Adjusting for glucose, potassium, and net fluid gain eliminated the apparent increase in mortality at 3 days observed with GIK infusion, suggesting a direct association with these factors. Administration of GIK infusion within 4 hours of symptom onset yielded no benefit compared with later initiation. CONCLUSIONS: Infusion of GIK provided no benefit and may cause early harm following STEMI. Avoidance of infusion-related hyperglycemia, hyperkalemia, and net fluid gain may be advisable in future studies of metabolic modulation in patients with STEMI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00064428.

Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non–ST-segment elevation acute coronary syndromes

Background: A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding. Objective: To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial. Design: Subgroup analysis of a randomized, controlled trial. Setting: Patients presenting to the hospital with non–ST-segment elevation ACS. Patients: 19 979 of the 20 078 patients in the OASIS 5 trial in whom creatinine was measured at baseline. Measurements: Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula. Results: The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. Limitations: Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States. Conclusions: The benefits of fondaparinux over enoxaparin when administered for non–ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.