The MI SYNTAX score for risk stratification in patients undergoing primary percutaneous coronary intervention for treatment of acute myocardial infarction: A substudy of the COMFORTABLE AMI trial.

BACKGROUND To investigate the performance of the MI Sxscore in a multicentre randomised trial of patients undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS The MI Sxscore was prospectively determined among 1132 STEMI patients enrolled into the COMFORTABLE AMI trial, which randomised patients to treatment with bare-metal (BMS) or biolimus-eluting (BES) stents. Patient- (death, myocardial infarction, any revascularisation) and device-oriented (cardiac death, target-vessel MI, target lesion revascularisation) major adverse cardiac events (MACEs) were compared across MI Sxscore tertiles and according to stent type. The median MI SXscore was 14 (IQR: 9-21). Patients were divided into tertiles of Sxscorelow (≤10), Sxscoreintermediate (11-18) and Sxscorehigh (≥19). At 1year, patient-oriented MACE occurred in 15% of the Sxscorehigh, 9% of the Sxscoreintermediate and 5% of the Sxscorelow tertiles (p<0.001), whereas device-oriented MACE occurred in 8% of the Sxscorehigh, 6% of the Sxscoreintermediate and 4% of the Sxscorelow tertiles (p=0.03). Addition of the MI Sxscore to the TIMI risk score improved prediction of patient- (c-statistic value increase from 0.63 to 0.69) and device-oriented MACEs (c-statistic value increase from 0.65 to 0.70). Differences in the risk for device-oriented MACE between BMS and BES were evident among Sxscorehigh (13% vs. 4% HR 0.33 (0.15-0.74), p=0.007 rather than those in Sxscorelow: 4% vs. 3% HR 0.68 (0.24-1.97), p=0.48) tertiles. CONCLUSIONS The MI Sxscore allows risk stratification of patient- and device-oriented MACEs among patients undergoing PPCI. The addition of the MI Sxscore to the TIMI risk score is of incremental prognostic value among patients undergoing PPCI for treatment of STEMI.

Predictors of adverse events among patients undergoing primary percutaneous coronary intervention: insights from a pooled analysis of the COMFORTABLE AMI and EXAMINATION trials

Aims: The aim of this study was to identify predictors of adverse events among patients with ST-elevation myocardial infarction (STEMI) undergoing contemporary primary percutaneous coronary intervention (PCI). Methods and results: Individual data of 2,655 patients from two primary PCI trials (EXAMINATION, N=1,504; COMFORTABLE AMI, N=1,161) with identical endpoint definitions and event adjudication were pooled. Predictors of all-cause death or any reinfarction and definite stent thrombosis (ST) and target lesion revascularisation (TLR) outcomes at one year were identified by multivariable Cox regression analysis. Killip class III or IV was the strongest predictor of all-cause death or any reinfarction (OR 5.11, 95% CI: 2.48-10.52), definite ST (OR 7.74, 95% CI: 2.87-20.93), and TLR (OR 2.88, 95% CI: 1.17-7.06). Impaired left ventricular ejection fraction (OR 4.77, 95% CI: 2.10-10.82), final TIMI flow 0-2 (OR 1.93, 95% CI: 1.05-3.54), arterial hypertension (OR 1.69, 95% CI: 1.11-2.59), age (OR 1.68, 95% CI: 1.41-2.01), and peak CK (OR 1.25, 95% CI: 1.02-1.54) were independent predictors of all-cause death or any reinfarction. Allocation to treatment with DES was an independent predictor of a lower risk of definite ST (OR 0.35, 95% CI: 0.16-0.74) and any TLR (OR 0.34, 95% CI: 0.21-0.54). Conclusions: Killip class remains the strongest predictor of all-cause death or any reinfarction among STEMI patients undergoing primary PCI. DES use independently predicts a lower risk of TLR and definite ST compared with BMS. The COMFORTABLE AMI trial is registered at: http://www.clinicaltrials.gov/ct2/show/NCT00962416. The EXAMINATION trial is registered at: http://www.clinicaltrials.gov/ct2/show/NCT00828087.

Additive effect of anemia and renal impairment on long-term outcome after percutaneous coronary intervention

INTRODUCTION Anemia and renal impairment are important co-morbidities among patients with coronary artery disease undergoing Percutaneous Coronary Intervention (PCI). Disease progression to eventual death can be understood as the combined effect of baseline characteristics and intermediate outcomes. METHODS Using data from a prospective cohort study, we investigated clinical pathways reflecting the transitions from PCI through intermediate ischemic or hemorrhagic events to all-cause mortality in a multi-state analysis as a function of anemia (hemoglobin concentration <120 g/l and <130 g/l, for women and men, respectively) and renal impairment (creatinine clearance <60 ml/min) at baseline. RESULTS Among 6029 patients undergoing PCI, anemia and renal impairment were observed isolated or in combination in 990 (16.4%), 384 (6.4%), and 309 (5.1%) patients, respectively. The most frequent transition was from PCI to death (6.7%, 95% CI 6.1-7.3), followed by ischemic events (4.8%, 95 CI 4.3-5.4) and bleeding (3.4%, 95% CI 3.0-3.9). Among patients with both anemia and renal impairment, the risk of death was increased 4-fold as compared to the reference group (HR 3.9, 95% CI 2.9-5.4) and roughly doubled as compared to patients with either anemia (HR 1.7, 95% CI 1.3-2.2) or renal impairment (HR 2.1, 95% CI 1.5-2.9) alone. Hazard ratios indicated an increased risk of bleeding in all three groups compared to patients with neither anemia nor renal impairment. CONCLUSIONS Applying a multi-state model we found evidence for a gradient of risk for the composite of bleeding, ischemic events, or death as a function of hemoglobin value and estimated glomerular filtration rate at baseline.

Three-year outcomes of percutaneous coronary intervention with next-generation zotarolimus-eluting stents for de novo coronary bifurcation lesions.

AIMS To investigate the outcomes of percutaneous coronary intervention (PCI) in bifurcation versus non-bifurcation lesions using the next-generation Resolute zotarolimus-eluting stent (R-ZES). METHODS AND RESULTS We analyzed 3-year pooled data from the RESOLUTE All-Comers trial and the RESOLUTE International registry. The R-ZES was used in 2772 non-bifurcation lesion patients and 703 bifurcation lesion patients, of which 482 were treated with a simple-stent technique (1 stent used to treat the bifurcation lesion) and 221 with a complex bifurcation technique (2 or more stents used). The primary endpoint was 3-year target lesion failure (TLF, defined as the composite of death from cardiac causes, target vessel myocardial infarction, or clinically-indicated target lesion revascularization [TLR]), and was 13.3% in bifurcation vs 11.3% in non-bifurcation lesion patients (adjusted P=.06). Landmark analysis revealed that this difference was driven by differences in the first 30 days between bifurcation vs non-bifurcation lesions (TLF, 6.6% vs 2.7%, respectively; adjusted P<.001), which included significant differences in each component of TLF and in-stent thrombosis. Between 31 days and 3 years, TLF, its components, and stent thrombosis did not differ significantly between bifurcation lesions and non-bifurcation lesions (TLF, 7.7% vs 9.0%, respectively; adjusted P=.50). CONCLUSION The 3-year risk of TLF following PCI with R-ZES in bifurcation lesions was not significantly different from non-bifurcation lesions. However, there was an increased risk associated with bifurcation lesions during the first 30 days; beyond 30 days, bifurcation lesions and non-bifurcation lesions yielded similar 3-year outcomes.

Differences in coronary risk factors, procedural characteristics, mortality and stent thrombosis between two all-comers percutaneous coronary intervention registries from Europe and Japan: a patient-level data analysis of the Bern-Rotterdam and j-Cypher registries

Aims: The reported rate of stent thrombosis (ST) after drug-eluting stent (DES) implantation varies among registries. To investigate differences in baseline characteristics and clinical outcome in European and Japanese all-comers registries, we performed a pooled analysis of patient-level data. Methods and results: The j-Cypher registry (JC) is a multicentre observational study conducted in Japan, including 12,824 patients undergoing SES implantation. From the Bern-Rotterdam registry (BR) enrolled at two academic hospitals in Switzerland and the Netherlands, 3,823 patients with SES were included in the current analysis. Patients in BR were younger, more frequently smokers and presented more frequently with ST-elevation myocardial infarction (MI). Conversely, JC patients more frequently had diabetes and hypertension. At five years, the definite ST rate was significantly lower in JC than BR (JC 1.6% vs. BR 3.3%, p<0.001), while the unadjusted mortality tended to be lower in BR than in JC (BR 13.2% vs. JC 14.4%, log-rank p=0.052). After adjustment, the j-Cypher registry was associated with a significantly lower risk of all-cause mortality (HR 0.56, 95% CI: 0.49-0.64) as well as definite stent thrombosis (HR 0.46, 95% CI: 0.35-0.61). Conclusions: The baseline characteristics of the two large registries were different. After statistical adjustment, JC was associated with lower mortality and ST.

Predicting 3-year mortality after percutaneous coronary intervention: updated logistic clinical SYNTAX score based on patient-level data from 7 contemporary stent trials

OBJECTIVES This study aimed to update the Logistic Clinical SYNTAX score to predict 3-year survival after percutaneous coronary intervention (PCI) and compare the performance with the SYNTAX score alone. BACKGROUND The SYNTAX score is a well-established angiographic tool to predict long-term outcomes after PCI. The Logistic Clinical SYNTAX score, developed by combining clinical variables with the anatomic SYNTAX score, has been shown to perform better than the SYNTAX score alone in predicting 1-year outcomes after PCI. However, the ability of this score to predict long-term survival is unknown. METHODS Patient-level data (N = 6,304, 399 deaths within 3 years) from 7 contemporary PCI trials were analyzed. We revised the overall risk and the predictor effects in the core model (SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction) using Cox regression analysis to predict mortality at 3 years. We also updated the extended model by combining the core model with additional independent predictors of 3-year mortality (i.e., diabetes mellitus, peripheral vascular disease, and body mass index). RESULTS The revised Logistic Clinical SYNTAX models showed better discriminative ability than the anatomic SYNTAX score for the prediction of 3-year mortality after PCI (c-index: SYNTAX score, 0.61; core model, 0.71; and extended model, 0.73 in a cross-validation procedure). The extended model in particular performed better in differentiating low- and intermediate-risk groups. CONCLUSIONS Risk scores combining clinical characteristics with the anatomic SYNTAX score substantially better predict 3-year mortality than the SYNTAX score alone and should be used for long-term risk stratification of patients undergoing PCI.

Prognostic implications of coronary calcification in patients with obstructive coronary artery disease treated by percutaneous coronary intervention: a patient-level pooled analysis of 7 contemporary stent trials

OBJECTIVE To investigate the long-term prognostic implications of coronary calcification in patients undergoing percutaneous coronary intervention for obstructive coronary artery disease. METHODS Patient-level data from 6296 patients enrolled in seven clinical drug-eluting stents trials were analysed to identify in angiographic images the presence of severe coronary calcification by an independent academic research organisation (Cardialysis, Rotterdam, The Netherlands). Clinical outcomes at 3-years follow-up including all-cause mortality, death-myocardial infarction (MI), and the composite end-point of all-cause death-MI-any revascularisation were compared between patients with and without severe calcification. RESULTS Severe calcification was detected in 20% of the studied population. Patients with severe lesion calcification were less likely to have undergone complete revascularisation (48% vs 55.6%, p<0.001) and had an increased mortality compared with those without severely calcified arteries (10.8% vs 4.4%, p<0.001). The event rate was also high in patients with severely calcified lesions for the combined end-point death-MI (22.9% vs 10.9%; p<0.001) and death-MI- any revascularisation (31.8% vs 22.4%; p<0.001). On multivariate Cox regression analysis, including the Syntax score, the presence of severe coronary calcification was an independent predictor of poor prognosis (HR: 1.33 95% CI 1.00 to 1.77, p=0.047 for death; 1.23, 95% CI 1.02 to 1.49, p=0.031 for death-MI, and 1.18, 95% CI 1.01 to 1.39, p=0.042 for death-MI- any revascularisation), but it was not associated with an increased risk of stent thrombosis. CONCLUSIONS Patients with severely calcified lesions have worse clinical outcomes compared to those without severe coronary calcification. Severe coronary calcification appears as an independent predictor of worse prognosis, and should be considered as a marker of advanced atherosclerosis.

4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention)

OBJECTIVES The aim of the study was to investigate 4-year outcomes and predictors of repeat revascularization in patients treated with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Minneapolis, Minnesota) and XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Abbott Park, Illinois) in the RESOLUTE (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) All-Comers trial. BACKGROUND Data on long-term outcomes of new-generation drug-eluting stents are limited, and predictors of repeat revascularization due to restenosis and/or progression of disease are largely unknown. METHODS Patients were randomly assigned to treatment with the R-ZES (n = 1,140) or the EES (n = 1,152). We assessed pre-specified safety and efficacy outcomes at 4 years including target lesion failure and stent thrombosis. Predictors of revascularization at 4 years were identified by Cox regression analysis. RESULTS At 4 years, the rates of target lesion failure (15.2% vs. 14.6%, p = 0.68), cardiac death (5.4% vs. 4.7%, p = 0.44), and target vessel myocardial infarction (5.3% vs. 5.4%, p = 1.00), clinically-indicated target lesion revascularization (TLR) (7.0% vs. 6.5%, p = 0.62), and definite/probable stent thrombosis (2.3% vs. 1.6%, p = 0.23) were similar with the R-ZES and EES. Independent predictors of TLR were age, insulin-treated diabetes, SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score, treatment of saphenous vein grafts, ostial lesions, and in-stent restenosis. Independent predictors of any revascularization were age, diabetes, previous percutaneous coronary intervention, absence of ST-segment elevation myocardial infarction, smaller reference vessel diameter, SYNTAX score, and treatment of left anterior descending, right coronary artery, saphenous vein grafts, ostial lesions, or in-stent restenosis. CONCLUSIONS R-ZES and EES demonstrated similar safety and efficacy throughout 4 years. TLR represented less than one-half of all repeat revascularization procedures. Patient- and lesion-related factors predicting the risk of TLR and any revascularization showed considerable overlap. (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention [RESOLUTE-AC]; NCT00617084).

Drug-eluting stents compared to bare-metal stents improve short-term survival in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a nationwide prospective analysis of the AMIS Plus registry

BACKGROUND Recently, it has been suggested that the type of stent used in primary percutaneous coronary interventions (pPCI) might impact upon the outcomes of patients with acute myocardial infarction (AMI). Indeed, drug-eluting stents (DES) reduce neointimal hyperplasia compared to bare-metal stents (BMS). Moreover, the later generation DES, due to its biocompatible polymer coatings and stent design, allows for greater deliverability, improved endothelial healing and therefore less restenosis and thrombus generation. However, data on the safety and performance of DES in large cohorts of AMI is still limited. AIM To compare the early outcome of DES vs. BMS in AMI patients. METHODS This was a prospective, multicentre analysis containing patients from 64 hospitals in Switzerland with AMI undergoing pPCI between 2005 and 2013. The primary endpoint was in-hospital all-cause death, whereas the secondary endpoint included a composite measure of major adverse cardiac and cerebrovascular events (MACCE) of death, reinfarction, and cerebrovascular event. RESULTS Of 20,464 patients with a primary diagnosis of AMI and enrolled to the AMIS Plus registry, 15,026 were referred for pPCI and 13,442 received stent implantation. 10,094 patients were implanted with DES and 2,260 with BMS. The overall in-hospital mortality was significantly lower in patients with DES compared to those with BMS implantation (2.6% vs. 7.1%,p < 0.001). The overall in-hospital MACCE after DES was similarly lower compared to BMS (3.5% vs. 7.6%, p < 0.001). After adjusting for all confounding covariables, DES remained an independent predictor for lower in-hospital mortality (OR 0.51,95% CI 0.40-0.67, p < 0.001). Since groups differed as regards to baseline characteristics and pharmacological treatment, we performed a propensity score matching (PSM) to limit potential biases. Even after the PSM, DES implantation remained independently associated with a reduced risk of in-hospital mortality (adjusted OR 0.54, 95% CI 0.39-0.76, p < 0.001). CONCLUSIONS In unselected patients from a nationwide, real-world cohort, we found DES, compared to BMS, was associated with lower in-hospital mortality and MACCE. The identification of optimal treatment strategies of patients with AMI needs further randomised evaluation; however, our findings suggest a potential benefit with DES.

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.

OBJECTIVES The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. BACKGROUND Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. METHODS Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. RESULTS Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women.