Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial.

BACKGROUND: Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI. METHODS: We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408. FINDINGS: Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups. INTERPRETATION: In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population. FUNDING: Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.

Nationwide trends in use and timeliness of diagnostic coronary angiography in acute coronary syndromes from 2005 to 2011: Does distance to invasive heart centres matter?

AIMS: To examine trends in the use of diagnostic coronary angiography according to distance from home to the nearest invasive heart centre following implementation of fast-track protocols and extensive pre-hospital triaging of acute coronary syndrome patients. METHODS AND RESULTS: We performed a register-based cohort study of all patients admitted to Danish hospitals with incident acute coronary syndrome in 2005-2011. Diagnostic coronary angiography within 60 days of admission was investigated according to distance tertiles (DTs) calculated as range from each patient's home to the nearest invasive heart centre (short DT: <22 km, medium DT: 22-65 km, long DT: >65 km). Cox proportional hazards models were applied.Among the 52,409 patients included, diagnostic coronary angiography was increasingly used during 2005-2011 (short DT: 76% to 81%; medium DT: 74% to 81%; long DT: 69% to 78%; all p-values for trend <0.001). Using the short DT as reference the adjusted hazard ratios for medium DT were 0.87 (0.84-0.89) for 2005-2007, 0.94 (0.90-0.98) for 2008-2009 and 0.94 (0.90-0.98) for 2010-2011. Corresponding figures for long DT were 0.74 (0.72-0.76) for 2005-2007, 0.87 (0.83-0.90) for 2008-2009 and 0.94 (0.90-0.98) for 2010-2011. Length of hospital stay, time to coronary angiography, and 60-day mortality decreased in all DT. CONCLUSIONS: This nationwide study found significant increases in diagnostic coronary angiography use over time in incident acute coronary syndrome patients with a relatively larger increase in patients residing farthest from an invasive heart centre. Additionally, selected quality of care measures improved in the entire cohort, suggesting a benefit of national clinical protocols.

Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease: a registry-based cohort study.

AIMS: To evaluate risk of hospitalization due to cardiovascular disease (CVD) and repeat coronary angiography (CAG) in stable angina pectoris (SAP) with no obstructive coronary artery disease (CAD) versus obstructive CAD, and asymptomatic reference individuals. METHODS AND RESULTS: We followed 11,223 patients with no prior CVD having a first-time CAG in 1998-2009 due to SAP symptoms and 5,695 asymptomatic reference individuals from the Copenhagen City Heart Study through registry linkage for 7.8 years (median). In recurrent event survival analysis, patients with SAP had 3-4-fold higher risk of hospitalization for CVD irrespective of CAG findings and cardiovascular comorbidity. Multivariable adjusted hazard ratios(95%CI) for patients with angiographically normal coronary arteries was 3.0(2.5-3.5), for angiographically diffuse non-obstructive CAD 3.9(3.3-4.6) and for 1-3-vessel disease 3.6-4.1(range)(all P<0.001). Mean accumulated hospitalization time was 3.5(3.0-4.0)(days/10 years follow-up) in reference individuals and 4.5(3.8-5.2)/7.0(5.4-8.6)/6.7(5.2-8.1)/6.1(5.2-7.4)/8.6(6.6-10.7) in patients with angiographically normal coronary arteries/angiographically diffuse non-obstructive CAD/1-, 2-, and 3-vessel disease, respectively (all P<0.05, age-adjusted). SAP symptoms predicted repeat CAG with multivariable adjusted hazard ratios for patients with angiographically normal coronary arteries being 2.3(1.9-2.9), for angiographically diffuse non-obstructive CAD 5.5(4.4-6.8) and for obstructive CAD 6.6-9.4(range)(all P<0.001). CONCLUSIONS: Patients with SAP symptoms and angiographically normal coronary arteries or angiographically diffuse non-obstructive CAD suffer from considerably greater CVD burdens in terms of hospitalization for CVD and repeat CAG compared with asymptomatic reference individuals even after adjustment for cardiac risk factors and exclusion of cardiovascular comorbidity as cause. Contrary to common perception, excluding obstructive CAD by CAG in such patients does not ensure a benign cardiovascular prognosis.

Symptoms of angina pectoris increase the probability of disability pension and premature exit from the workforce even in the absence of obstructive coronary artery disease.

AIMS: To evaluate probabilities of disability pension (DP) and premature exit from the workforce (PEW) in patients with stable angina symptoms and no obstructive coronary artery disease (CAD) at angiography compared with obstructive CAD and asymptomatic reference individuals. METHODS AND RESULTS: We followed 4303 patients with no prior cardiovascular disease having a first-time coronary angiography (CAG) in 1998-2009 due to stable angina symptoms and 2772 reference individuals from the Copenhagen City Heart Study, all aged <65 years, through registry linkage until 2009 for DP and PEW. Five-year age-adjusted DP-free survival probabilities for reference individuals, patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1 stenotic coronary vessel (1VD), 2VD, and 3VD, respectively, were 0.96, 0.88, 0.84, 0.82, 0.85, and 0.78 in women and 0.98, 0.90, 0.89, 0.89, 0.88, and 0.87 in men. Significant predictors of DP were higher age, angina symptoms, higher body mass index, diabetes, smoking, job status, non-marital status in men, lower income, lower educational level, and co-morbidity. Compared with the reference population, probabilities of DP and PEW were significantly increased in all patients with no gender difference (P > 0.2 for interaction). Thus, in pooled multivariable-adjusted analysis, patients referred to CAG for angina had a three-fold higher probability of DP and ~50% higher probability of PEW, with little difference between patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1VD, 2VD, 3VD, the hazard ratios for DP being 2.7, 3.0, 3.3, 3.1, and 3.2 (all P < 0.001) and for PEW being 1.3, 1.4, 1.5, 1.6, and 1.6 (all P < 0.05). CONCLUSION: Patients with angina symptoms and angiographically normal coronary arteries, diffuse non-obstructive CAD, or obstructive CAD at angiography have a three-fold increased probability of DP regardless of angiographic findings.

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

AIMS: Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. METHODS AND RESULTS: We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. CONCLUSION: Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

Long-term clinical outcome in STEMI patients treated with primary PCI and drug-eluting or bare-metal stents: insights from a high-volume single-center registry.

OBJECTIVE: Use of drug-eluting stents (DES) in patients with ST-elevation myocardial infarction (STEMI) during routine primary percutaneous coronary intervention (pPCI) is controversial. METHODS: From January 2004 to July 2008, a total of 2,155 STEMI patients were treated with pPCI [DES or bare-metal stent (BMS)] at a single high-volume invasive center. We present 4-year outcomes in this observational registry study. RESULTS: A total of 1,725 were treated with DES and 430 with BMS. Patients treated with DES were younger and had more complex angiographic characteristics compared to BMS patients. Patients treated with DES had lower adjusted risk of target lesion revascularization (TLR) [hazard ratio (HR) = 0.68; 95% confidence interval (CI): 0.40-0.98; p = 0.04], but had a trend toward increased risk of definite stent thrombosis (HR = 1.96; 95% CI: 0.83-4.61; p = 0.12). No difference was found when evaluating all-cause mortality and non-fatal myocardial infarction. CONCLUSIONS: In this study, we set out to evaluate the independent impact of DES or BMS treatment on long-term clinical outcomes in STEMI patients treated with pPCI in a real-life setting. DES use was associated with a reduced risk of TLR, but a trend toward increased risk of stent thrombosis was found. However, this safety issue did not translate into an increased risk of death or overall non-fatal myocardial infarction for DES patients.

Impact of abciximab in elderly patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention: an observational registry study.

BACKGROUND: An increasing proportion of patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are classified as elderly (aged ≥70 years). The glycoprotein IIb/IIIa inhibitor abciximab is known to reduce adverse outcomes in patients aged <70 years with high-risk ACS undergoing PCI, but conflicting findings relating to its effects in the elderly have been reported. OBJECTIVE: The aim of this study was to evaluate the effect of abciximab in elderly high-risk ACS patients undergoing PCI. METHODS: From our dedicated PCI registry we identified 2068 ACS patients with high-risk lesions that were treated with PCI. Baseline data were collected prospectively. All-cause mortality, target vessel revascularization (TVR), myocardial infarction (MI), and the combination of these were primary study endpoints. All endpoints within 1 year after PCI were registered and validated. The population was subsequently stratified according to age and use of abciximab. RESULTS: Elderly patients constituted 42% of the total population. They presented with more co-morbidities, were less frequently treated with abciximab and had a higher risk of reaching the combined endpoint and higher all-cause mortality than younger patients. The age/abciximab stratified analysis revealed no effect of abciximab on any of the endpoints in elderly patients (combined endpoint: no abciximab 22.6% vs abciximab 23.4%, p=0.85; all-cause mortality: no abciximab 15.4% vs abciximab 15.9%, p=0.91; TVR: no abciximab 3.4% vs abciximab 5.5%, p=0.21; MI: no abciximab 7.0% vs abciximab 8.5%, p=0.54), whereas all-cause mortality and the risk of reaching the combined endpoint were significantly reduced in younger patients (combined endpoint: no abciximab 14.0% vs abciximab 9.4%, p=0.03; all-cause mortality: no abciximab 4.5% vs abciximab 1.7%, p=0.02; TVR: no abciximab 5.5% vs abciximab 4.3%, p=0.39; MI: no abciximab 7.2% vs abciximab 6.6%, p=0.80). These findings were confirmed in our adjusted analyses. CONCLUSIONS: In this large observational study we found no benefit of abciximab treatment in elderly high-risk ACS patients who underwent PCI. These findings should be taken into consideration when deciding on the treatment strategy for elderly ACS patients undergoing PCI.

Three-year follow-up in a subset of high-risk patients randomly assigned to off-pump versus on-pump coronary artery bypass surgery: the Best Bypass Surgery trial.

OBJECTIVE: To evaluate off-pump versus on-pump coronary artery bypass grafting (CABG) in patients with three-vessel disease and a high-risk operative profile. DESIGN: A randomised clinical trial. SETTING: Rigshospitalet, University Hospital, Copenhagen, Denmark. PARTICIPANTS: 341 patients with three-vessel disease and a EuroSCORE of 5 or greater. Main exclusion criteria were previous heart surgery, poor left ventricular function (ejection fraction <30%), or unstable preoperative condition. INTERVENTION: CABG performed with versus without cardiopulmonary bypass. MAIN OUTCOME MEASURE: The primary outcome was a composite of major adverse cardiac and cerebrovascular events (MACCE) including all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke and coronary reintervention. RESULTS: MACCE occurred in 69 (40%) patients allocated to off-pump versus 54 (33%) patients allocated to on-pump CABG during the median 3.7 years of follow-up (HR 1.22; 95% CI 0.86 to 1.75; p=0.26). All-cause mortality was significantly increased in the off-pump group (24% vs 15%; HR 1.66, 95% CI 1.02 to 2.73; p=0.04), but cardiac-related death was not significantly different (10% vs 7%; HR 1.30, 95% CI 0.64 to 2.66; p=0.47). An insignificant trend towards a reduction in myocardial infarction after off-pump CABG was observed (7% vs 14%; HR 0.53, 95% CI: 0.27 to 1.04; p=0.06). CONCLUSIONS: No significant difference in the primary outcome of MACCE was found between off-pump and on-pump CABG. However, mortality seemed higher after off-pump CABG. TRIAL REGISTRATION: http://clinicaltrials.gov/number, NCT00120991.

Efficacy of post-operative clopidogrel treatment in patients revascularized with coronary artery bypass grafting after myocardial infarction.

OBJECTIVES: The objective of this study was to examine the clinical efficacy of clopidogrel treatment on death and recurrent myocardial infarction (MI) among MI patients revascularized by coronary artery bypass graft surgery (CABG). BACKGROUND: The benefit from post-operative clopidogrel in CABG-treated MI patients is largely unknown. METHODS: All patients admitted with first-time MI between 2002 and 2006, treated with CABG within 180 days after admission, were identified by nationwide administrative registers. Clopidogrel treatment was determined by claimed prescriptions after discharge from surgery. Risk of death or recurrent MI, and of a combined end point of the 2, were assessed by cumulative incidence and Cox proportional hazards model. A propensity score-matched subgroup analysis was done. RESULTS: We included 3,545 patients, and of these, 957 (27.0%) were treated with clopidogrel after CABG. Mean follow-up was 466 ± 144 days. Among patients treated with clopidogrel, 39 (4.1%) died or experienced a recurrent MI, whereas that occurred in 203 (7.8%) patients without clopidogrel (log-rank p = 0.0003). Hazard ratio was 0.59 (95% confidence interval [CI]: 0.42 to 0.85) for patients treated with clopidogrel, with no-clopidogrel as reference. By propensity score, of 945 patients with or without clopidogrel treatment who were matched, death or recurrent MI occurred in 38 (4.0%) patients with clopidogrel and 57 (6.0%) without clopidogrel (log-rank p = 0.05). Corresponding hazard ratio was 0.67 (95% CI: 0.44 to 1.00) for clopidogrel users, with no-clopidogrel as reference. CONCLUSIONS: Among MI patients revascularized by CABG, only 27% received clopidogrel after discharge. Clopidogrel-treated patients had a lower risk of the combined end point of death or recurrent MI. Focus on discharge clopidogrel treatment of these patients should be made.

Comparably improved health-related quality of life after total arterial revascularization versus conventional coronary surgery--Copenhagen arterial revascularization randomized patency and outcome trial.

OBJECTIVE: We compared health-related quality of life up to 11 months after coronary artery bypass grafting using total arterial revascularization versus conventional coronary surgery. METHODS: In this randomized single-center trial, 161 patients underwent total arterial revascularization using single or bilateral internal thoracic artery (ITA) and radial artery grafts versus 170 patients conventionally revascularized using left ITA and saphenous vein grafts. Preoperatively, and at 3 and 11 months, postoperatively, patients filled in the generic questionnaire Short Form-36 (SF-36). RESULTS: The mean age was 59±8 years and 39 were women (12%). Median EuroSCORE (European System for Cardiac Risk Evaluation) was 2 (interquartile range 1-4). More than 90% of patients filled in the questionnaire at all three time points. Preoperatively, all scores were lower (P<0.001) than for a sample of the general Danish population. On all scales of the SF-36, there was statistically significant improvement at 3 and 11 months in both groups. For 'social functioning', the improvement following total arterial revascularization was significantly higher than following conventional revascularization (P=0.01). For total arterial revascularization, there were also not statistically significant improvements for 'physical component summary' (P=0.09), 'bodily pain' (P=0.07) and 'vitality' (P=0.08). CONCLUSION: Health-related quality of life up to 1 year after total arterial revascularization is equal or slightly better than results after conventional coronary surgery.

Impact of abciximab in diabetic patients with acute coronary syndrome who undergo percutaneous coronary intervention: results from a high-volume, single-center registry.

BACKGROUND: The prevalence of diabetes mellitus (DM) and ischemic heart disease is increasing. Moreover, patients with DM experiencing an acute coronary syndrome (ACS) have an increased risk of adverse outcomes after revascularization compared to non-diabetics. Data have suggested that the glycoprotein IIb/IIIa inhibitor abciximab might be more efficient in diabetics than in those without DM. METHODS AND RESULTS: We evaluated the effect of abciximab in patients with DM and ACS from our percutaneous coronary intervention (PCI) registry. Among 5,003 patients with ACS who underwent PCI, 629 had DM. Patients were followed for up to 3 years with regard to mortality, myocardial infarction (MI) and target vessel revascularization (TVR). Despite a more severe risk profile, adjusted analyses revealed a marked reduction in TVR (hazard ratio [HR], 0.30; confidence interval [CI], 0.14-0.63; p = 0.002), mortality (HR, 0.53; CI, 0.28-0.97; p = 0.04) and the combined endpoint, also including MI (HR, 0.53; CI, 0.35-0.79; p = 0.002) in the DM patients who received abciximab compared to those who did not, resulting in a risk of reaching the endpoints at levels similar to the risk in patients without DM. The reduction in MI was not significant. CONCLUSION: Our findings suggest that abciximab administered to ACS patients with DM during PCI reduces mortality and the need for TVR to rates similar to those seen in patients without DM and far below the risk in DM patients who do not receive abciximab.

Intracoronary compared to intravenous bolus abciximab during primary percutaneous coronary intervention in ST-segment Elevation Myocardial Infarction (STEMI) patients reduces 30-day mortality and target vessel revascularization: a randomized trial.

BACKGROUND: Abciximab is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been questioned. Preliminary studies suggest that IC-bolus is superior, probably due to high local concentration. In this study, we assess the short-term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI. METHODS: In 2006-2008, we randomized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion. Primary end-points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end-points were bleeding complications. RESULTS: The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end-point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). CONCLUSION: IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus.

Long-term effects of invasive treatment in patients with a post-thrombolytic Q-wave myocardial infarction.

OBJECTIVES: The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. DESIGN: Patients (N=751) with post-thrombolytic Q-wave myocardial infarction and inducible ischemia (angina pectoris or silent myocardial ischemia) were randomized to a deferred invasive treatment (balloon angioplasty or coronary bypass surgery) or medical treatment. Vital status and non-fatal cardiac events defined as hospitalization caused by acute cardiac events were recorded for a median of 11.4 years. RESULTS: Survival was significantly improved in patients receiving invasive treatment compared to patients treated medically (hazard ratio 0.85 (95% confidence limits 0.73-0.99), p=0.034). Subgroup analysis showed a reduction of non-fatal cardiac events and improved survival among the patients with post-infarction angina pectoris and not among the patients with silent myocardial ischemia. CONCLUSIONS: A deferred invasive treatment strategy improves survival compared to medical treatment in patients with inducible myocardial ischemia after a post-thrombolytic Q-wave myocardial infarction.

Graft patency after off-pump versus on-pump coronary artery surgery in high-risk patients.

OBJECTIVE: To compare angiographic graft patency in high-risk patients randomly allocated to off-pump vs. on-pump coronary artery bypass grafting (CABG). DESIGN: From a randomised, single-centre clinical trial including patients undergoing isolated first-time coronary bypass surgery a subgroup of patients were scheduled to 1-year coronary angiographic follow-up. Patients had 3-vessel disease and a EuroSCORE > or =5. We evaluated graft patency using a patency index (percentage of patent grafts out of the total number of grafts in each patient). RESULTS: One-year angiography was performed in 34 patients undergoing off-pump surgery and 35 patients undergoing on-pump surgery. The mean number of distal anastomoses was 3.38+/-0.65 in the off-pump group versus 3.46+/-0.61 in the on-pump group (NS). The number of patients without graft failure was 22 in the off-pump group and 24 in the on-pump group (NS). The overall patency index was 85% in the off-pump group versus 87% in the on-pump group with a mean difference of -2.1%, 95% confidence interval -12.9 to 8.7 (NS). CONCLUSIONS: In patients with 3-vessel disease and a high-risk profile we found no statistically significant difference in graft patency between off-pump and on-pump CABG at 1-year coronary angiographic follow-up.

Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study.

BACKGROUND: The optimal duration of clopidogrel treatment after percutaneous coronary intervention (PCI) is unclear. We studied the risk of death or recurrent myocardial infarction (MI) in relation to 6- and 12-months clopidogrel treatment among MI patients treated with PCI. METHODS: Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens. RESULTS: The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06). CONCLUSIONS: We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.

No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery: the best bypass surgery trial.

BACKGROUND: Off-pump coronary artery bypass grafting compared with coronary revascularization with cardiopulmonary bypass seems safe and results in about the same outcome in low-risk patients. Observational studies indicate that off-pump surgery may provide more benefit in high-risk patients. Our objective was to compare 30-day outcomes in high-risk patients randomized to coronary artery bypass grafting without or with cardiopulmonary bypass. METHODS AND RESULTS: We randomly assigned 341 patients with a EuroSCORE > or = 5 and 3-vessel coronary disease to undergo coronary artery bypass grafting without or with cardiopulmonary bypass. Patients were followed through the Danish National Patient Registry. The primary outcome was a composite of adverse cardiac and cerebrovascular events (ie, all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention). An independent adjudication committee blinded to treatment allocation assessed the outcomes. Baseline characteristics were well balanced between groups. The mean number of grafts per patient did not differ significantly between groups (3.22 in off-pump group and 3.34 in on-pump group; P=0.11). Fewer grafts were performed to the lateral part of the left ventricle territory during off-pump surgery (0.97 versus 1.14 after on-pump surgery; P=0.01). No significant differences in the composite primary outcome (15% versus 17%; P=0.48) or the individual components were found at 30-day follow-up. CONCLUSIONS: Both off- and on-pump coronary artery bypass grafting can be performed in high-risk patients with low short-term complications. CLINICAL TRIAL REGISTRATION- clinicaltrials.gov. Identifier: NCT00120991.

Field triage reduces treatment delay and improves long-term clinical outcome in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVES: We evaluated the independent impact of field triage on treatment delay and long-term clinical outcome in a large contemporary, consecutive population of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND: Reduction of treatment delay is crucial for patients with STEMI. METHODS: From January 2005 to July 2008, 1,437 STEMI patients were treated with pPCI at a single high-volume invasive center. We present the 1-year outcome in this observational registry study. RESULTS: A total of 616 patients were admitted by field triage and 821 by emergency departments. Baseline and angiographic variables were similar in the 2 populations. Patients admitted by field triage had a significantly shorter median door-to-balloon time compared with patients admitted by emergency department triage (83 min, interquartile range 67 to 100 min vs. 103 min, interquartile range 80 to 135 min; p<0.001). Door-to-balloon times of less than the recommended 90 min were achieved in 61% of field triage patients, but only in 36% of nonfield-triage patients (p<0.001). After adjustment for relevant baseline variables, patients admitted by field triage had a reduced risk of reaching the combined end point of all-cause mortality or nonfatal myocardial infarction (hazard ratio: 0.67; 95% confidence interval: 0.46 to 0.97; p=0.035). CONCLUSIONS: This study shows that field triage of STEMI patients to pPCI significantly reduces treatment delay and improves outcome. These results emphasize the value of field triage as an important tool in the quest to improve clinical outcomes in STEMI patients undergoing pPCI.

Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data.

BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens. METHODS: By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. FINDINGS: During a mean follow-up of 476.5 days (SD 142.0), 1891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 1.33 (95% CI 1.11-1.59) for clopidogrel, 1.23 (0.94-1.61) for vitamin K antagonist, 1.47 (1.28-1.69) for aspirin plus clopidogrel, 1.84 (1.51-2.23) for aspirin plus vitamin K antagonist, 3.52 (2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08-5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18.4%) of 38 960 patients without non-fatal bleeding (HR 3.00, 2.75-3.27, p<0.0001). INTERPRETATION: In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment. FUNDING: Danish Heart Foundation and the Danish Medical Research Council.

One-year results of total arterial revascularization vs. conventional coronary surgery: CARRPO trial.

AIMS: To investigate clinical and angiographic outcomes after coronary surgery using total arterial revascularization (TAR). METHODS AND RESULTS: We randomized 331 patients with multivessel or isolated left main disease to TAR [internal thoracic (ITA) and radial arteries] vs. conventional revascularization (CR) using left ITA and vein grafts. The primary angiographic outcome was the patency index: number of patent grafts (<50% stenosed) divided by number of constructed grafts. One-year angiography was complete for 83% of patients. Mean patency index (+/-SD) was 87 +/- 22% in the TAR group and 88 +/- 18% in the conventional group (P = 0.52). In 72% of TAR patients and 67% of the conventional group, all grafts were patent (P = 0.45). Multiple imputation of missing angiographic data did not influence on results. Within 1 year, 37 (23%) TAR patients and 43 (25%) conventional group patients suffered cardiac events (HR 1.09, 95% CI 0.70-1.69, P = 0.70). One patient (0.6%) in the TAR group and two (1.2%) in the conventional group died (P = 1.00). CONCLUSION: Within 1 year post-operatively, TAR seems at least as safe and effective as CR. Prolonged follow-up will reveal whether this is sustained or superior results of TAR can justify a more general use.

Clinical reinfarction according to infarct location and reperfusion modality in patients with ST elevation myocardial infarction. A DANAMI-2 long-term follow-up substudy.

OBJECTIVES: To evaluate clinical reinfarction during a 3-year follow-up after randomization to primary angioplasty versus fibrinolysis in anterior and non-anterior ST elevation myocardial infarction (STEMI). METHODS: Clinical reinfarction was prospectively assessed by an endpoint committee blinded to the study treatment. RESULTS: At 30 days, primary angioplasty compared with fibrinolysis reduced the reinfarction rate both in anterior STEMI patients (n = 823; 2.5 vs. 5.6%, p = 0.02) and in non-anterior STEMI patients (n = 743; 0.8 vs. 7.4%, p < 0.001). After 3 years, the reduction in reinfarction rate was no longer present in anterior STEMI patients (11.2 vs. 11.2%, p = 0.86), but persisted in non-anterior STEMI patients (5.2 vs. 13.5%, p < 0.001). Reinfarction after anterior STEMI carried a higher mortality than reinfarction after non-anterior STEMI (37.6 vs. 15.3%, p = 0.01). Independent predictors of death were: age [hazard ratio (HR) per 1-year increase in age = 1.08 (1.07-1.09)], clinical reinfarction [HR = 5.15 (3.57-7.43)], anterior index STEMI [HR = 1.65 (1.24-2.19)], and Killip class > or =2 [HR = 1.42 (1.01-2.00)]. The additional late reinfarctions after angioplasty for anterior STEMI were located within the angioplasty-treated target segment. Anterior STEMI patients had smaller mean target vessel diameter, which was associated with reinfarction. CONCLUSIONS: Clinical reinfarction is an independent predictor of death. The early superiority of primary angioplasty over fibrinolysis on reinfarction rate after anterior STEMI diminished during long-term follow-up.