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Background: COMBO (OrbusNeich Medical, Hong Kong) is a dual-therapy coronary stent featuring sirolimus as antiproliferative drug and an anti-CD34+ antibody coating to attract endothelial progenitor cells favoring rapid stent re-endothelization. The Mega COMBO collaboration aimed to evaluate the performance of the COMBO stent in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI)., Methods: Patient-level data of subjects undergoing PCI with the COMBO stent from the REMEDEE-Trial, REMEDEE-OCT, HARMONEE, REDUCE, SORT OUT X, REMEDEE-Registry and MASCOT studies were pooled together. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction (TV-MI) or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes were the individual components of the primary endpoint and stent thrombosis (ST). Endpoints were evaluated against performance goals based on the EAPCI (the European Association of Percutaneous Coronary Intervention) recommendations for new drug-eluting stents., Results: A total of 6753 patients (mean age 63.7 ± 11.4 years, 23% women) were included. At 1-year follow-up, TLF occurred in 303 (4.6%) patients. The rates of cardiovascular death, TV-MI, and CD-TLR were 1.3%, 1.8%, and 2.5%, respectively. The rate of definite/probable ST was 0.73%, early ST (<1 month) was 0.48%, while late ST (1-12 months) was 0.26%. The performance goals were met for all of the evaluated endpoints., Conclusions: This large patient-level pooled analysis provides a comprehensive outline of the performance of the dual-therapy COMBO stent. The low rates of primary and secondary endpoints suggest that this stent technology may be a good alternative to other contemporary drug eluting coronary stent platforms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: Periprocedural myocardial infarction (PMI), a severe complication of Percutaneous Coronary Intervention (PCI) procedures, has a negative prognostic effect, both at short and long-term follow-up. So far, adenosine's role in preventing PMI has shown contrasting results. A genetic variant of ADORA2A receptor, 1976 C＞T, has been suggested as a potential determinant of the interindividual response to adenosine, thus conditioning its potential benefits on PMI. In our study, we investigated whether the ADORA2A 1976 C＞T polymorphism is associated with PMI occurrence in patients undergoing coronary stenting., Methods: The study included consecutive patients undergoing PCI at the Azienda Ospedaliera-Universitaria "Maggiore della Carità," Novara, Italy, between January 2010 and January 2016. Their genetic status was assessed using polymerase chain reaction (PCR) and restriction-fragment-length-polymorphism technique. Myonecrosis biomarkers were measured at intervals from 6 to 48 hours. PMI was defined as CKMB increased 3 times over the Upper Limit of Normal (ULN), or 50% of pre-PCI value; periprocedural myonecrosis was defined as troponin I increased 3 times over the ULN or by 50% of the baseline value., Results: We included 1,104 patients undergoing PCI, 863 (78.2%) of whom carried the ADORA2A T-allele. No difference was found for the main demographic, clinical features, or biochemistry parameters. However, C-carriers had lower statin therapy use (p=0.008) and lower HDL-cholesterol levels (p=0.01). Homozygous C/C patients had more frequent multivessel disease (p=0.03), longer lesions (p=0.01) and Type C lesions (p=0.01), thus requiring more complex procedures. After correction for baseline confounding factors at multivariate analysis, there was no difference in myocardial necrosis according to the ADORA2A genotype (p=0.40). In contrast, PMI tended to increase in the homozygous C/C population (p=0.06), but this trend was attenuated at multivariate analysis after correction for baseline confounding factors (C/C: OR[95%CI]=1.52 [0.88-2.6], p=0.14)., Conclusions: Our study showed that the polymorphism rs5751876 of the ADORA2A receptor is associated with a higher prevalence of complex coronary lesions and multivessel disease. However, it does not significantly influence the occurrence of periprocedural MI or myonecrosis.

Patients undergoing staged percutaneous coronary intervention (SPCI) are exposed to extended duration of antiplatelet therapy, and a novel aspirin-free antiplatelet regimen after SPCI should be specifically evaluated among these patients. This is a prespecified substudy of the GLOBAL LEADERS which is a randomized, open-label trial, comparing an experimental regimen of 1-month dual antiplatelet therapy (DAPT; ticagrelor and aspirin) followed by 23-month ticagrelor monotherapy to a reference regimen of 12-month DAPT followed by 12-month aspirin monotherapy. Patients were stratified according to whether or not SPCI was performed. The impact of the timing of SPCI on clinical outcomes was also investigated. Of 15,968 randomized patients, 1,651 patients underwent SPCI within 3 months. These patients with SPCI had a significantly higher risk of bleeding and ischemic endpoints than those without SPCI. In patients undergoing SPCI, the primary endpoint (composite of all-cause death or new Q-wave myocardial infarction at 2 years) and secondary safety endpoint (Bleeding Academic Research Consortium [BARC]-defined bleeding 3 or 5) were similar in the 2 regimens. However, in patients presenting with acute coronary syndrome (ACS), the experimental regimen reduced a risk of BARC 3 or 5 bleeding (1.8% vs 4.5%; HR 0.387; 95% CI 0.179 to 0.836; p = 0.016). In patients undergoing SPCI later than 10 days after index procedure, this risk reduction was still prominent (0.8% vs 2.3%; HR 0.321; 95% CI 0.116 to 0.891; p = 0.029). In conclusion, patients undergoing SPCI are at high risk and may need special attention from clinicians. In ACS patients undergoing SPCI, a novel aspirin-free antiplatelet regimen appears to be associated with a lower bleeding risk than with standard DAPT., Competing Interests: Conflict of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Vitamin D deficiency has been implicated in the progression of atherosclerosis and acute thrombotic events. We aimed at evaluating the impact of vitamin D deficiency on periprocedural myocardial infarction (PMI) in patients undergoing percutaneous coronary interventions (PCI). We included 934 patients undergoing non-urgent PCI. Assessment of myocardial biomarkers was performed from 6 to 48 h after PCI. PMI was defined as Creatine Kinase-MB increase by 3 times the Upper Limit Normal or by 50% of an elevated baseline value, periprocedural myocardial damage as Troponin I increase by 3 × ULN or 50% of baseline. Patients were divided according to vitamin D tertiles values (<10.2 ng/ml; 10.2-18.7 ng/ml; ≥18.8 ng/ml). Lower tertiles values of vitamin D were associated with age (p = 0.04), female gender, (p = 0.001), and a higher cardiovascular risk profile. Lower vitamin D levels related with PCI of descending anterior coronary artery or bypass vein grafts (p = 0.03), treatment of bifurcations (p = 0.05) and side branch loss (p = 0.05) and inversely with direct stenting (p = 0.002). However, lower vitamin D levels did not influence the risk of PMI (adjusted OR [95% CI] = 0.81[0.65,1.18], p = 0.09) or periprocedural myocardial damage (adjusted OR [95% CI] = 0.93[0.77,1.13], p = 0.48). Similar results were achieved when considering the severity of vitamin D deficiency. Therefore, in patients undergoing PCI, no association was observed between vitamin D deficiency and the risk of periprocedural MI and myocardial damage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Recent trials have failed to demonstrate any clinical benefit from pre-treatment with dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary interventions, (PCI), even in the setting of acute coronary syndrome. However, suboptimal platelet inhibition during (PCI) has been shown to enhance the risk of acute ischemic complications, such as stent thrombosis and periprocedural myocardial infarction (PMI), thus raising the attention on the potential advantages of adjunctive glycoprotein IIbIIIa inhibitors to obviate to the delayed onset of action of oral antiplatelet drugs. The aim of the present study was then to evaluate the impact of platelet reactivity and pre-procedural DAPT on PMI in patients undergoing PCI with adjunctive tirofiban., Methods: In a consecutive cohort of patients undergoing PCI with tirofiban (intracoronary/intravenous ± prolonged infusion), periprocedural myonecrosis was defined as troponin I increase by 3 times the ULN or by 50% of an elevated baseline value, whereas PMI as CKMB increase by 3 times the ULN or 50% of baseline. Platelet function was assessed by impedance aggregometry., Results: A total of 168 patients were included, 77 (45.8%) of whom were on DAPT at the time of PCI. Patients on DAPT had more often a history of previous PCI (p = 0.03), higher ACS at admission (p < 0.001) and creatinine levels (p = 0.03). Coronary calcifications and type C lesions were more frequent in patients without DAPT (p = 0.02 and p = 0.03, respectively), as much as TIMI flow < 3 (p = 0.03), while procedural characteristics were comparable. Baseline platelet reactivity was significantly reduced in DAPT treated patients (p < 0.001 for ASPI, COL and ADP tests). However the rate of periprocedural myonecrosis did not differ according to pre-procedural DAPT (68.4%vs 67%, p = 0.87; adjusted OR[95%CI] = 1.34[0.71-2.53], p = 0.36) and neither the occurrence of PMI (13.3% vs 12.6%, p = 0.99; adjusted OR[95%CI] = 1.24[0.51-3.1], p = 0.64). Furthermore, baseline platelet reactivity was similar in patients with and without PMI/myonecrosis with no relationship between platelet function and Troponin I peak., Conclusion: In patients undergoing PCI with adjunctive GP IIb-IIIa inhibitors, preprocedural DAPT and baseline platelet reactivity are not associated to the risk of periprocedural myocardial infarction or myonecrosis. These data further support the role of periprocedural Gp IIb-IIIa inhibitors in order to overcome any suboptimal inhibition of platelet aggregation at the time of the procedure due to drug-resistance or delayed (downstream) administration of ADP antagonists, especially in complex high-risk procedures., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: Deferred revascularisation based upon fractional flow reserve (FFR >0.80) is associated with a low incidence of target lesion failure (TLF). Whether deferred revascularisation is also as safe in diabetes mellitus (DM) patients is unknown., Methods: All DM patients and the next consecutive Non-DM patients who underwent a FFR-assessment between 1/01/2010 and 31/12/2013 were included, and followed until 1/07/2015. Patients with lesions FFR >0.80 were analysed according to the presence vs. absence of DM, while patients who underwent index revascularisation in FFR-assessed or other lesions were excluded. The primary endpoint was the incidence of TLF; a composite of target lesion revascularisation (TLR) and target vessel myocardial infarction (TVMI)., Results: A total of 250 patients (122 DM, 128 non-DM) who underwent deferred revascularisation of all lesions (FFR >0.80) were compared. At a mean follow up of 39.8 ± 16.3 months, DM patients compared to non-DM had a higher TLF rate, 18.1 vs 7.5 %, logrank p ≤ 0.01, Cox regression-adjusted HR 3.65 (95 % CI 1.40-9.53, p < 0.01), which was largely driven by a higher incidence of TLR (17.2 vs. 7.5 %, HR 3.52, 95 % CI 1.34-9.30, p = 0.01), whilst a non-significant but numerically higher incidence of TVMI (6.1 vs. 2.0 %, HR 3.34, 95 % CI 0.64-17.30, p = 0.15) was observed., Conclusions: This study, the largest to directly compare the clinical outcomes of FFR-guided deferred revascularisation in patients with and without DM, shows that DM patients are associated with a significantly higher TLF rate. Whether intravascular imaging, additional invasive haemodynamics or stringent risk factor modification may impact on this higher TLF rate remains unknown.

Despite the demonstrated benefits of Prasugrel, a new generation thienopyridine, in the prevention of thrombotic complications after percutaneous coronary interventions (PCI) for Acute Coronary Syndromes (ACS), its use is still precluded to those many patients arriving to the cath lab pre-treated with Clopidogrel. Conclusive data on the strategy of switching from Clopidogrel to Prasugrel are still missing, therefore we aimed to perform a meta-analysis of current studies evaluating the safety and efficacy of switching from Clopidogrel to Prasugrel (PS) as compared to a standard thienopyridine therapy with Clopidogrel or Prasugrel in patients undergoing PCI. Literature archives and main scientific sessions' abstracts were scanned for studies comparing a switching strategy from Clopidogrel to Prasugrel vs. Prasugrel or Clopidogrel. Primary efficacy endpoint was overall mortality. Secondary endpoints were: non-fatal myocardial infarction and definite/probable stent thrombosis. Safety endpoint was the rate of major bleedings according to a per-protocol definition. A total of 12 studies, involving 3956 patients, were included. Among them, 1396 patients (35.3%), received Prasugrel after a Clopidogrel treatment (PS), while 2560 (64.7%) received either Prasugrel or Clopidogrel. The switch from Clopidogrel to Prasugrel was in the majority of the studies periprocedural. The mortality was numerically lower, but not statistically significant, in the PS group as compared with patients who did not switch (1.7% vs. 3.8%, OR [95% CI] = 0.68 [0.40,1.15], p = 0.15, phet = 0.61), without any relationship with patients' risk profile (r = -0.68 [-2.09, 0.73], p = 0.35). Similar results were obtained for secondary efficacy endpoints and at sensitivity analysis in the majority of subgroups evaluated. Moreover, the PS strategy did not increase major bleedings as compared with standard therapy (1.4% vs. 2.5%, OR [95% CI = 0.70 [0.39, 1.25], p = 0.23, phet = 0.6). The present meta-analysis confirms that, among patients undergoing PCI, switching from Clopidogrel to Prasugrel may be safely performed and therefore should be encouraged among patients eligible to Prasugrel.

Background: Several concerns have emerged about the higher risk of very late stent thrombosis (ST) with first generation drug-eluting stent (DES), especially in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). New generation DES have demonstrated reduction in ST at mid-term follow-up, however no data are available on long-term follow-up. Therefore, the aim of this study was to report long-term results of the RACES-MI trial conducted to compare Everolimus-Eluting Stent (EES) vs Sirolimus-Eluting Stent (SES) in patients undergoing primary PCI., Methods: The RACES-MI trial enrolled consecutive STEMI patients admitted within 12h of symptom onset, undergoing primary PCI with stent implantation at a tertiary center with 24-hour primary PCI capability, who were randomly assigned to SES or EES. Primary endpoint of this analysis is major adverse cardiac events (MACE) at long-term follow-up. Secondary endpoints are 1) death; 2) reinfarction; 3) definite or probable ST; 4) target-vessel revascularization (TVR) at long-term follow-up., Results: From April 2007 to May 2009 500 patients with STEMI were randomized to EES (n=250) or SES (n=250). No difference was observed between the groups either in baseline clinical characteristics, in the number of implanted stent or total stent length per patient. However, a larger reference diameter was observed with SES (3.35±0.51 mm vs 3.25±0.51 mm, p=0.001), whereas patients randomized to EES received Gp IIb-IIIa inhibitors more often (54.4% vs 42.4%, p=0.006). At long-term follow-up (2132±528 days), EES was associated with a significant reduction in MACE (23.8 vs 34.1%, adjusted p=0.028), ST (2.5% vs 7.7%, adjusted p=0.009), without any difference in death (8.7% vs 11.4%, adjusted p=0.47), reMI (9.3% vs 13.1%; adjusted p=0.18) and TVR (8.6% vs 12.3%, adjusted p=0.31)., Conclusions: This study shows that among STEMI patients undergoing primary PCI EES, as compared to SES, is associated with significant reduction in MACE and ST at long-term follow-up., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Drug-eluting stent has been shown to reduce the risk of repeated revascularization. However, as shown for first-generation drug-eluting stent, they may be counterbalanced by a potential higher risk of stent thrombosis, especially among ST-segment elevation myocardial infarction patients. In addition, diabetes has been shown to be an independent predictor of poor survival and repeated target vessel revascularization. No data have been reported so far on the long-term benefits and safety of new-generation drug-eluting stent in ST-segment elevation myocardial infarction according to diabetes. Therefore, the aim of this study was to evaluate whether diabetes may impact on the benefits from everolimus-eluting stent versus first-generation drug-eluting stent in patients undergoing primary angioplasty., Methods: We combined data from two randomized trials (PaclitAxel or Sirolimus-Eluting Stent vs Bare-Metal Stent in Primary Angioplasty and randomized comparison of everolimus-eluting stents and sirolimus-eluting stents in patients with ST elevation myocardial infarction) including consecutive ST-segment elevation myocardial infarction patients admitted within 12 h of symptom onset undergoing primary angioplasty and stent implantation at a tertiary centre with 24-h primary percutaneous coronary intervention capability. Primary endpoint of this study was major adverse cardiac events at 3-year follow-up. Secondary endpoints were as follows: (1) death, (2) reinfarction, (3) definite or probable ST and (4) target vessel revascularization at 3-year follow-up. No patient was lost to follow-up., Results: Our population is represented by 680 ST-segment elevation myocardial infarction patients treated with drug-eluting stent (180 enrolled in the PaclitAxel or Sirolimus-Eluting Stent vs Bare-Metal Stent in Primary Angioplasty trial, treated with first-generation drug-eluting stent, and 500 patients in the randomized comparison of everolimus-eluting stents and sirolimus-eluting stents in patients with ST elevation myocardial infarction, randomized to everolimus-eluting stent or sirolimus-eluting stent). Diabetes was observed in a total of 178 patients (26.1%) and associated with higher major adverse cardiac events, mortality, reinfarction, stent thrombosis and target vessel revascularization. Similar outcome was observed in terms of overall major adverse cardiac events, mortality, recurrent myocardial infarction, target vessel revascularization, with everolimus-eluting stent as compared to first-generation drug-eluting stent in both diabetic and non-diabetic patients, whereas everolimus-eluting stent was associated with a significantly lower rate of stent thrombosis only in diabetic patients (1.6% vs 9.6%, hazard ratio (95% confidence interval) = 0.15 (0.02-0.98), p = 0.04) whereas no difference was observed in non-diabetic patients., Conclusion: This study shows that among ST-segment elevation myocardial infarction patients undergoing primary angioplasty, diabetes is associated with a significantly worse outcome at 3-year follow-up. A similar outcome was observed between everolimus-eluting stent and first-generation drug-eluting stent in non-diabetic patients, whereas among diabetic patients everolimus-eluting stent was associated with a significant reduction in stent thrombosis., (© The Author(s) 2015.)

Background: Current guidelines recommend culprit-only revascularisation (COR) in haemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel (MV) disease. Contrarily, growing body of evidence available from recent randomised controlled trials (RCTs) demonstrates improved outcomes with complete MV-percutaneous coronary intervention (PCI)., Methods and Results: We performed a meta-analysis of RCTs comparing complete MV-PCI with non-complete MV-PCI in STEMI and MV disease. Complete MV-PCI was defined as revascularisation to non-infarct-related artery lesions during index procedure, non-complete MV-PCI-encompassed COR and staged approaches. Multiple databases and congress proceedings from major cardiovascular societies' meetings were screened for relevant studies. Primary endpoint was the composite of major adverse cardiac events (MACE) typically defined as death, recurrent myocardial infarction (MI) and repeat revascularisation. Secondary endpoints were cardiovascular mortality, recurrent MI and repeat revascularisation. Outcomes were analysed at longest available follow-up with differences accounted for with adjusted models by person-years. Seven RCTs (N=1303) were included. The median follow-up was 12 months. Complete MV-PCI reduced the odds of MACE compared with non-complete MV-PCI (OR (95% CIs) 0.59 (0.36 to 0.97), p=0.04) driven by reduction in recurrent MI (0.48 (0.27 to 0.85), p=0.01) and repeat revascularisation (0.51 (0.31 to 0.84), p=0.008). Complete MV-PCI was associated with a non-significant trend towards reduced cardiovascular mortality (0.54 (0.26 to 1.10), p=0.09) as well. In a sensitivity analysis, none of the baseline clinical variables significantly influenced overall estimates., Conclusions: In STEMI and MV disease, complete MV-PCI as compared with non-complete strategy reduces MACE by 41%, driven by a 52% reduction in recurrent MI and 49% reduction in repeat revascularisation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Alterations of glucose homeostasis have been reported to occur even in non-diabetic patients, thus increasing the risk of cardiovascular events and worsening the outcome after an acute myocardial infarction (AMI). Still debated is the role of impaired glucose control in patients undergoing percutaneous coronary intervention (PCI), as hyperglycemia, represents an important pro-thrombotic stimulus, increasing platelet reactivity and potentially procedural complications. Therefore, the aim of our study was to assess the association between glycosylated hemoglobin and periprocedural myocardial infarction (PMI) in non-diabetic patients undergoing PCI., Methods: We included patients without history of diabetes undergoing elective PCI. PMI was defined as creatine kinase-MB increase by 3 times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as Troponin I increase by 3× ULN or 50% of baseline., Results: Our population is represented by 1199 patients, who were divided according to tertile values of glycosylated hemoglobin (HbA1c). Higher HbA1c was associated with ageing (p<0.001), hypertension (p=0.005), previous myocardial infarction (p=0.009), PCI (p<0.001) or CABG (p=0.001), treatment with diuretics (p<0.001), higher levels of glycemia (p<0.001) and white blood cells (p=0.02), multivessel coronary artery disease (p=0.03), higher rate of instent restenosis (p=0.02). HbA1c did not impact on periprocedural myocardial infarction (p=0.85; adjusted OR [95% CI]=0.91 [0.74-1.12], p=0.38) or myonecrosis (p=0.69; adjusted OR [95% CI]=0.95 [0.80-1.13], p=0.56). Similar results were obtained fasting glycemia for PMI (p=0.82, adjusted OR [95% CI]=0.90 [0.71-1.14], p=0.37) and myonecrosis (p=0.21, adjusted OR [95% CI]=1.02 [0.84-1.24], p=0.84) and confirmed in high-risk subsets of patients., Conclusions: In non-diabetic patients undergoing elective PCI, neither glycosylated hemoglobin levels nor fasting glycemia are associated with the risk of periprocedural myocardial infarction and necrosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Concerns have emerged regarding a higher risk of stent thrombosis after drug-eluting stent (DES) implantation, especially in the setting of ST-segment elevation myocardial infarction (STEMI). Therefore, we performed a meta-analysis based on individual patient data to evaluate long-term safety and effectiveness of paclitaxel-eluting stent (PES) as compared to bare metal stents (BMS) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. We examined all completed randomized trials on PES for STEMI. Individual patient data were obtained from six trials. We performed survival analyses with the use of Cox-regression analysis stratified according to trial. Kaplan-Meier survival curves are presented with event rates reported as estimated probabilities. A subsequent landmark analysis was performed for patients who were event-free at 1-year follow-up in order to define outcome in terms of early (≤1 year) and late (>1 year) events. A total of six trials were finally included in the meta-analysis with 4435 patients, 2875 (64.8 %) assigned to PES and 1560 (35.2 %) to BMS. No significant differences in baseline characteristics were observed between the two groups. However, a significantly higher percentage of patients in the DES group were on dual antiplatelet therapy during 3-year follow-up, as compared to BMS. At long-term follow-up (1,095 [1,090-1,155] days), no significant difference between PES and BMS was observed in mortality (9.2 vs 11.9 %, respectively, HR [95 % CI] = 0.84 [0.67, 1.06], p = 0.15, pheterogeneity = 0.59), reinfarction (8.8 vs 7 %, respectively; HR [95 % CI] = 1.10 [0.84, 1.44], p = 0.51, pheterogeneity = 0.32), stent thrombosis (6.7 vs 4.0 % respectively, HR [95 % CI] = 1.13 [0.82, 1.55], p = 0.45, pheterogeneity = 0.99) and TVR (11.9 vs 20.0 %; HR [95 % CI] = 0.64 [0.54, 0.77], p < 0.0001, pheterogeneity = 0.25). Landmark analysis showed that PES was associated with a significantly higher rate of very late reinfarction (>1 year) (5.6 vs 3.9 %, HR [95 % CI] = 1.61 [1.05-2.47], p = 0.03, pheterogeneity = 0.51], very late ST (2.9 vs 1.1 %, HR [95 % CI] = 1.88 [1.00-3.54], p = 0.05, pheterogeneity = 0.94]. The present pooled patient-level meta-analysis demonstrates that among STEMI patients undergoing primary PCI, PES compared to BMS is associated with a significant reduction in TVR at long-term follow-up. Although there were no differences in cumulative mortality, reinfarction or stent thrombosis, the incidence of very late reinfarction and stent thrombosis was increased with PES.

There has been a considerable effort to improve adjunctive antithrombotic therapies to reperfusion strategies in the treatment of ST-segment elevation Myocardial Infarction (STEMI). Therefore, the aim of this article is to provide a critical and updated overview of recent advances on adjunctive antithrombotic therapies in patients undergoing primary angioplasty for STEMI. Due to very low costs, early Unfractionated Heparin (UFH) plus additional periprocedural administration should still be regarded as the gold standard in antithrombotic therapy, whereas subsequent subcutaneous administration of Low Molecular Weight Heparins (LMWHs) or fondaparinux should be considered, especially in patients at higher risk of thromboembolic complications. Periprocedural bivalirudin should be considered instead of a strategy of combined UFH and Glycoprotein (Gp) IIb/IIIa inhibitors, especially among patients at higher risk of bleeding complications. New oral ADP antagonists should be administrated as early as possible soon after diagnosis, whereas the use of clopidogrel should be limited to the cases when the new ADP antagonists are not available or contraindicated. However, rivaroxaban has obtained indication for Acute Coronary Syndromes (ACS), and therefore its combination with aspirin and clopidogrel will gain recognition especially among STSegment Elevation Myocardial Infarction (STEMI) patients. Future trials are needed to compare different possible strategies with oral antithrombotic therapies and in particular optimal duration, especially in the era of new DES that have been shown to reduce the risk of stent thrombosis. Early Gp IIb/IIIa inhibitor use may be considered as upstream therapy especially in high-risk patients, whereas the choice of periprocedural administration may be based on thrombus burden or in case of impaired haemodynamic conditions that may compromise oral drug absorption. Overall, a more aggressive antithrombotic approach should be considered within the first hours from symptom onset, when the considerable viability justifies aggressiveness. The use of radial approach and potential protamine administration should be considered in order to minimize the risk of bleeding complications. Due to the very low mortality currently achieved by primary angioplasty and stenting, a further reduction in short or mediumterm mortality would be not easy to demonstrate. Therefore, additional endpoints, such as infarct size and myocardial perfusion, may be considered in future randomized trials especially for the evaluation of new periprocedural antithrombotic therapies among patients undergoing mechanical revascularization for STEMI.

Background: The Zwolle Risk Score (ZRS) identifies ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) eligible for early discharge. We aimed to investigate whether baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) is also able to identify these patients and could improve future risk strategies., Methods and Results: PPCI patients included in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) II study were candidates (N=861). We analyzed whether ZRS and baseline NT-proBNP predicted 30-day mortality and assessed the occurrence of major adverse cardiac events (MACEs) and major bleeding. Receiver operating characteristic curve analysis was used to assess discriminative accuracy for ZRS, NT-pro-BNP, and their combination. After multiple imputation, 845 patients were included. Both ZRS >3 (hazard ratio [HR]=9.42; P<0.001) and log NT-pro-BNP (HR=2.61; P<0.001) values were associated with 30-day mortality. On multivariate analysis, both the ZRS (HR=1.41; 95% confidence interval [CI]=1.27 to 1.56; P<0.001) and log NT-proBNP (HR=2.09; 95% CI=1.59 to 2.74; P<0.001) independently predicted death at 30 days. The area under the curve for 30-day mortality for combined ZRS/NT-proBNP was 0.94 (95% CI=0.90 to 0.99), with optimal predictive values of a ZRS ≥2 and a NT-proBNP value of ≥200 pg/mL. Using these cut-off values, 64% of the study population could be identified as very low risk with zero mortality at 30 days follow-up and low occurrence of MACEs and major bleeding between 48 hours and 10 days (1.3% and 0.6%, respectively)., Conclusion: Baseline NT-proBNP identifies a large group of low-risk patients who may be eligible for early (48- to 72-hour) discharge, whereas optimal predictive accuracy is reached by the combination of both baseline NT-proBNP and ZRS., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI)., Methods and Results: A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed., Conclusions: Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Eosinophils have been involved in a wide spectrum of pro-inflammatory and pro-thrombotic conditions, with the development of cardiovascular complications in a significant proportion of hypereosinophilic patients. However, no study has so far evaluated the impact of eosinophils levels on periprocedural myocardial infarction (PMI) in patients undergoing non-urgent percutaneous coronary interventions (PCI), that was, then, aim of current study., Methods: In a consecutive cohort of patients, myonecrosis biomarkers were dosed at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined as troponin I increase by 3 times the ULN or by 50% of an elevated baseline value, whereas PMI as CKMB increase by 3 times the ULN or 50% of baseline., Results: Our population is represented by 1543 patients who were divided according to tertiles of absolute eosinophils count (AEC ≤ 0.1; 0.1-0.2; >0.2 × 10ˆ3/ml). Higher AEC was related to male gender (p = 0.002), arterial hypertension (p = 0.02), diabetes (p = 0.001), previous coronary revascularization (p = 0.003 for PCI, p = 0.03 for CABG), treatment with ARBs, beta-blockers, diuretics and ASA (p < 0.001), statins (p = 0.02), calcium antagonists (p = 0.05), glycosylated hemoglobin (p < 0001), creatinine levels (p = 0.001) and platelet count (p = 0.01), while inversely with acute presentation (p < 0.001), glycemia (p = 0.03), HDL-cholesterol and C-reactive protein (p = 0.02). AEC related with multivessel coronary artery disease (p = 0.05), lesion length (p = 0.01), drug eluting stents implantation (p = 0.001) and use of kissing balloon technique (p = 0.05), while inversely to intracoronary thrombus (p < 0.001) and thrombectomy (p = 0.04). AEC did not influence the occurrence of PMI (p = 0.06, adjusted OR [95% CI] = 1.06 [0.86-1.31], p = 0.57) or myonecrosis (p = 0.15, adjusted OR [95% CI] = 1.06 [0.88-1.27], p = 0.53). Results were confirmed at subgroup analysis in higher-risk subsets of patients., Conclusion: In patients undergoing non-urgent PCI, eosinophils levels are not associated with the occurrence of periprocedural myocardial infarction or myonecrosis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Several concerns have emerged on the higher risk of in-stent thrombosis after drug-eluting stent (DES) implantation, especially in the setting of STEMI patients. Few data have even been reported in high-risk patients, such as those with anterior MI. Therefore this represents the aim of the current study., Methods: The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. No language restrictions were enforced., Results: Individual patient's data were obtained from 11 out of 13 trials, including a total of 2,782 patients with anterior MI [1,739 or 62.5% randomized to DES and 1,043 or 37.5% randomized to bare-metal stent (BMS)]. At long-term follow-up, no significant benefit was observed with DES as compared to BMS in terms of mortality [9.8 vs 10.9%, HR (95% CI) = 0.81 (0.61, 1.07), p = 0.13, p heterogeneity = 0.18], reinfarction [8.8 vs 6.4%, respectively; HR (95% CI) = 1.14 (0.80, 1.61), p = 0.47, p heterogeneity = 0.82], and stent thrombosis [5.6 vs 5%, OR (95% CI) = 0.88 (0.59, 1.30), p = 0.51, p heterogeneity = 0.65], whereas DES was associated with a significant reduction in terms of target-vessel revascularization (TVR) [13.7 vs 23.4%; OR (95% CI) = 0.56 (0.46, 0.69), p < 0.0001, p het = 0.81] that was observed at both early (within 1 year) [7 vs 14.7%, HR (95% CI) = 0.56 (0.46, 0.69), p < 0.0001, p het = 0.81] and late (>1 year) follow-up [7.2 vs 9%, HR (95% CI) = 0.67 (0.47, 0.96), p = 0.03, p het = 0.96]., Conclusions: This study showed that among patients with anterior STEMI undergoing primary angioplasty, SES and PES, as compared to BMS, are associated with a significant reduction in TVR at long-term follow-up. No concerns were found with the use of first-generation DES in terms of mortality.

Objectives: The aim of the current study was to compare everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing primary angioplasty., Background: Drug-eluting stents may offer benefits in terms of repeat revascularization. However, as shown for first-generation drug-eluting stents, they may be counterbalanced by a potential higher risk of stent thrombosis, especially among patients with ST-segment elevation myocardial infarction (STEMI). No data have been reported so far on the long-term benefits and safety of the new generation of drug-eluting stents in STEMI., Methods: Consecutive STEMI patients admitted within 12 h of symptom onset and undergoing primary angioplasty and stent implantation at a tertiary center with 24-h primary percutaneous coronary intervention capability were randomly assigned to SES or EES. The primary endpoint was a major adverse cardiac event at 3-year follow-up. The secondary endpoints were death, reinfarction, definite or probable stent thrombosis, and target vessel revascularization at 3-year follow-up. No patient was lost to follow-up., Results: From April 2007 to May 2009, 500 patients with STEMI were randomized to EES (n = 250) or SES (n = 250). No difference was observed in terms of baseline demographic and clinical characteristics between the groups. No difference was observed between the groups in terms of number of implanted stents per patient or total stent length. However, a larger reference diameter was observed with SES (3.35 ± 0.51 mm vs. 3.25 ± 0.51 mm, p = 0.001), whereas patients randomized to EES more often received glycoprotein IIb/IIIa inhibitors (54.4% vs. 42.4%, p = 0.006). Follow-up data were available in all patients (1,095 ± 159 days). No significant difference was observed between EES and SES in major adverse cardiac events (16% vs. 20.8%, adjusted hazard ratio [HR]: 0.75 [95% confidence interval (CI): 0.5 to 1.13], p = 0.17), cardiac death (4.4% vs. 5.6%, adjusted HR: 0.77 [95% CI: 0.35 to 1.71], p = 0.53), recurrent MI (6.4% vs. 10%, adjusted HR: 0.62 [95% CI: 0.33 to 1.16], p = 0.13), and target vessel revascularization (4.8% vs. 4.8%, adjusted HR: 1.00 [95% CI: 0.45 to 2.32], p = 0.99). However, EES was associated with a significant reduction in stent thrombosis (1.6% vs. 5.2%, adjusted HR: 0.3 [95% CI: 0.1 to 0.92], p = 0.035)., Conclusions: This study shows that among STEMI patients undergoing primary angioplasty, EES has similar efficacy as SES, but is associated with a significant reduction in stent thrombosis. (Randomized Comparison of Everolimus Eluting Stents and Sirolimus Eluting Stent in Patients With ST Elevation Myocardial Infarction [RACES-MI]; NCT01684982)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Hypertension is a well known risk factor for atherosclerosis. However, data on the prognostic impact of hypertension in patients with ST elevation myocardial infarction (STEMI) are inconsistent and mainly related to studies performed in the thrombolytic era, with very few data in patients undergoing primary angioplasty. Therefore, the aim of the current study was to evaluate the impact hypertension on clinical outcome in STEMI patients undergoing primary PCI with BMS or DES., Methods: Our population is represented by 6298 STEMI patients undergoing primary angioplasty included in the DESERT database from 11 randomized trials comparing DES vs BMS for STEMI., Results: Hypertension was observed in 2764 patients (43.9%), and associated with ageing (p<0.0001), female gender (p<0.001), diabetes (p<0.0001), hypercholesterolemia (p<0.0001), previous MI (p=0.002), previous revascularization (p=0.002), longer time-to-treatment (p<0.001), preprocedural TIMI 3 flow, and with a lower prevalence of smoking (41% vs 53.9%, p<0.001) and anterior MI (42% vs 45.9%, p=0.002). Hypertension was associated with impaired postprocedural TIMI 0-2 flow (Adjusted OR [95% CI]=1.22 [1.01-1.47], p=0.034). At a follow-up of 1,201 ± 440 days, hypertension was associated with higher mortality (adjusted HR [95% CI]=1.24 [1.01-1.54], p=0.048), reinfarction (adjusted HR [95% CI]=1.31 [1.03-1.66], p=0.027), stent thrombosis (adjusted HR [95% CI]=1.29 [0.98-1.71], p=0.068) and TVR (adjusted HR [95% CI]=1.22 [1.04-1.44], p=0.013)., Conclusions: This study showed that among STEMI patients undergoing primary angioplasty with DES or BMS, hypertension is independently associated with impaired epicardial reperfusion, mortality, reinfarction and TVR, and a trend in higher ST., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim was to investigate whether a strategy of direct drug-eluting stent (DES) implantation without pre-dilation is associated with a reduced incidence of restenosis compared with CS with pre-dilation or provisional stenting (PS)., Background: Previous studies were performed comparing direct stenting (DS) with conventional stenting (CS) after pre-dilation; however, none of these in the DES era. Therefore, the STRESSED (direct Stenting To reduce REStenosis in Stent Era with Drug elution) study was designed and carried out., Methods: A total of 600 patients with angina pectoris or recent myocardial infarction were randomized to a DS, CS, or PS strategy. The primary endpoint was the mean minimal lumen diameter at 9-month follow-up angiography. Secondary endpoints were clinical procedural success defined as angiographic success without in-hospital major adverse cardiac events (MACE), and MACE at 9-month and 2-year follow-up., Results: Stent implantation in the DS group was 98%, 99% in the CS group, and 77% in the PS group. Percutaneous coronary intervention success was 99% in all groups. The minimal lumen diameter at 9-month follow-up was 2.12 ± 0.58 mm (DS), 2.17 ± 0.67 mm (CS), and 1.99 ± 0.69 mm (PS), p = 0.556 for comparison of DS with CS, p = 0.073 for comparison of DS with PS. The absolute difference was -0.05 (DS to CS), 95% confidence interval: -0.19 to -0.09, p = 0.48 and 0.13 (DS to PS), confidence interval: -0.02 to -0.27, p = 0.087. Restenosis was found in 3.4% (DS), 6.7% (CS), and 11.5% (PS), p = 0.025. At 9-month and 2-year follow-up, MACE occurred in 6.8% and 11.5% (DS), 4.6% and 10.3% (CS), and 7.6% and 13.8% (PS) (p = 0.439 and 0.536), respectively., Conclusions: Direct DES implantation compared with conventional DES implantation did not reduce restenosis. Provisional stenting, however, was associated with a higher rate of restenosis. This did not translate into a difference in the rate of MACE. (STRESSED study: direct Stenting To reduce REStenosis in Stent Era with Drug elution; ISRCTN41213536)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Acute coronary syndromes (ACSs) represent a high-risk condition, as enhanced platelet reactivity importantly influences myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). In fact, higher rate of periprocedural myocardial infarction (PMI) and reduced event-free survival have been reported in these patients. The single nucleotide polymorphism Leu33Pro of platelet glycoprotein IIIa has been related to an increased platelet reactivity, a lower response to antiplatelet agents and higher risk of stent restenosis. Therefore, our aim was to evaluate the impact of this polymorphism on PMI in patients undergoing PCI for non-ST-segment elevation MI (NSTEMI). Our population is represented by 478 consecutive patients undergoing coronary angioplasty for NSTEMI. Cardiac biomarkers were monitored at intervals from 8 to 48 h after the procedure. Genetic analysis was performed to assess the presence of Leu33Pro polymorphism. A total of 156 patients (32.6%) were polymorphic. Clinical features did not differ according to genetic status, neither pharmacological treatment pre and during angioplasty. PlA carriers had lower rate of calcifications (P = 0.01) and higher coronary tortuosity (P = 0.03) at angiography and underwent more frequently to thrombectomy (P = 0.05). PCI-related complications did not differ according to genotype. Leu33Pro polymorphism was not associated with increased risk of periprocedural myonecrosis and PMI even after correction for baseline differences, [odds ratio (OR) (95% confidence interval (CI) = 0.70 (0.44-1.13), P = 0.15 for PMI and OR (95% CI) = 0.77 (0.53-1.11), P = 0.17 for myonecrosis, respectively]. Results were confirmed in high-risk subgroups of patients. In conclusion, among patients undergoing PCI for ACS, the polymorphism Leu33Pro of platelet glycoprotein IIIa is not associated with increased risk of PMI.

It was the purpose of this study to assess the effect of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) on reperfusion and clinical outcome in a real-world STEMI population. The decision to use TA (Export catheter, Medtronic) was at the discretion of the treating cardiologist. The primary endpoint was mortality at short (in-hospital) and long term (one year) follow-up. Secondary end points were post-PCI TIMI flow, residual ST deviation and enzymatic infarct size. Cox proportional hazard models (propensity-weighted) and logistic regression analysis were used to adjust for known covariates, associated with mortality. We performed a retrospective analysis of prospectively collected data on 2,552 consecutive PPCI-treated STEMI patients between 2007 and 2010. Use of TA increased from 6.9% in 2007 to 62.2% in 2010 (p<0.001). TA was performed in 899 patients (35.2%). In-hospital and one-year mortality rates were 3.0% and 6.0%, respectively, in the TA group and 3.5% and 7.6% in the no-TA group. After multivariate analysis, TA was not significantly associated with in-hospital mortality (adjusted odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.33-1.49, p=0.36) nor one year mortality (adjusted hazard ratio [HR]: 0.75, 95%CI: 0.47-1.20, p=0.23) or cardiac mortality (HR: 0.81; 95%CI: 0.45-1.46, p=0.49). After matching on the propensity score, the HR in the TA group for one year mortality was 0.70 (95%CI: 0.41-1.20, p=0.19) and for one-year cardiac mortality 0.70 (95%CI: 0.36-1.34, p=0.28). In conclusion, no significant relationship of TA with one of the secondary end points was found. The use of TA increased over the last years but clinical outcome was similar in both groups (TA vs no-TA) in this large cohort of real-world, unselected STEMI patients.

Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI) and large interests have been focused on platelets in order to prevent such a complication. The single nucleotide polymorphism Leu33Pro of platelet glycoprotein IIIa has been related to an increased platelet reactivity, a lower response to antiplatelet agents and higher risk of stent restenosis. Therefore, aim of our study was to evaluate the impact of this polymorphism on PMI in elective patients undergoing PCI. Our population is represented by 422 consecutive patients with cardiac biomarkers within normality undergoing elective PCI. We measured cardiac biomarkers (CK-MB and Troponin I) at baseline, and 8, 24 and 48 hours after the procedure. For all subjects, we performed genetic analysis to assess the presence of Leu33Pro polymorphism. A total of 136 patients (32.2%) were polymorphic. Those patients were younger (p = 0.03) and more often dislypidemic (p = 0.01). Angiographic features did not differ according to genetic status. Pharmacological treatment pre and during angioplasty was similar. PCI-related complications did not differ according to genotype, with the only exception of higher rate of distal embolization in polymorphic patients. However, Leu33Pro polymorphism was not associated with increased risk of periprocedural myonecrosis and PMI even after correction for baseline differences, (respectively OR = 1.22 [0.81-1.84], p = 0.34 for myonecrosis and OR = 1.66 [0.85-3.23]; p = 0.14 for PMI). At subgroup analysis, the Leu33Pro substitution was associated with higher risk of PMI only among diabetics (adjusted OR = 4.46 [1.12-17.76], p = 0.03). Among patients undergoing elective PCI, the polymorphism Leu33Pro of platelet glycoprotein IIIa is associated with increased risk of PMI only in diabetic patients.

Aim: Poorer outcomes in women with ST-elevation myocardial infarction (STEMI) are often attributed to gender differences in baseline characteristics. However, these may be age dependent. We examined the importance of gender in separate age groups of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI)., Methods and Results: Data of 6746 consecutive patients with STEMI admitted for PPCI between 1998 and 2008 in our hospital were evaluated. Age was stratified into two groups, <65 years (young group) and ≥65 years (elderly). Endpoints were enzymic infarct size as well as 30-day and 1 year mortality. We studied a total of 4991 (74.0%) men and 1755 (26.0%) women; 40% of women were <65 years and 60% of men were <65 years of age. In the elderly group (≥65 years), women had more frequently diabetes and hypertension while they smoked less frequently than men. Younger women smoked more often than similarly aged men and had more hypertension. At angiography, single-vessel disease and TIMI 3 flow before PPCI was more present in younger women than men, whereas these differences were not found in the older age group. Patient delay before admission was shorter in men at all ages, while women had lower creatine kinase levels. Younger women had a higher mortality after 30 days (HR 2.1, 95% CI 1.3-3.4) and at 1 year (HR 1.7, 95% CI 1.2-2.6), whereas in the older age group women mortality rates were higher at 30 days (HR 1.5, 95% CI 1.1-2.0) but not at 1 year (HR 1.2, 95% CI 0.9-1.5). After multivariate analysis, 1-year mortality remained significantly higher in women at younger age (HR 1.7, 95% CI 1.1-2.5). Patient delay before admission was shorter in men in both age groups. Creatine kinase levels were in both age groups higher in men., Conclusions: Differences in mortality between men and women with STEMI treated with PPCI are age dependent. Although young women have less obstructive coronary artery disease and more often TIMI 3 flow before PCI (suggesting a lower risk), survival was worse compared to similarly aged men. Women had a longer patient delay compared to men, but this was not related to gender-specific mortality.

Objectives: To investigate the safety and efficacy of durable polymer drug eluting stents (DES) and biodegradable polymer biolimus eluting stents (biolimus-ES)., Design: Network meta-analysis of randomised controlled trials., Data Sources and Study Selection: Medline, Google Scholar, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) database search for randomised controlled trials comparing at least two of durable polymer sirolimus eluting stents (sirolimus-ES) and paclitaxel eluting stents (paclitaxel-ES), newer durable polymer everolimus eluting stents (everolimus-ES), Endeavor and Resolute zotarolimus eluting stents (zotarolimus-ES), and biodegradable polymer biolimus-ES., Primary Outcomes: Safety (death, myocardial infarction, definite or probable stent thrombosis) and efficacy (target lesion and target vessel revascularisation) assessed at up to one year and beyond., Results: 60 randomised controlled trials were compared involving 63,242 patients with stable coronary artery disease or acute coronary syndrome treated with a DES. At one year, there were no differences in mortality among devices. Resolute and Endeavor zotarolimus-ES, everolimus-ES, and sirolimus-ES, but not biodegradable polymer biolimus-ES, were associated with significantly reduced odds of myocardial infarction (by 29-34%) compared with paclitaxel-ES. Compared with everolimus-ES, biodegradable polymer biolimus-ES were associated with significantly increased odds of myocardial infarction (by 29%), while Endeavor zotarolimus-ES and paclitaxel-ES were associated with significantly increased odds of stent thrombosis. All investigated DES were similar with regards to efficacy endpoints, except for Endeavor zotarolimus-ES and paclitaxel-ES, which were associated with significantly increased the odds of target lesion and target vessel revascularisations compared with other devices. Direction of results beyond one year did not diverge from the findings for up to one year follow-up. Bayesian probability curves showed a gradient in the magnitude of effect, with everolimus-ES and Resolute zotarolimus-ES offering the highest safety profiles., Conclusions: The newer durable polymer everolimus-ES and Resolute zotarolimus-ES and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES; however, for safety endpoints, differences become apparent, with everolimus-ES and Resolute zotarolimus-ES emerging as the safest stents to date.

Introduction: Primary angioplasty has improved survival as compared to thrormbolysis. However, bleeding complications still represent the Achille's heel, mainly related to access site. Although the radial approach is getting larger consensus for elective percutaneous procedures, its safety and advantages in the setting of ST-segment elevation (STEMI) is controversial. Therefore, the aim of the current study was to perform a comprehensive meta-analysis of randomized and non randomized trials comparing radial vs transfemoral approach in primary angioplasty for STEMI., Methods: The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to October 2012. No language restrictions were enforced., Results: A total of 27 trials were finally included, with 29,194 patients (4685 enrolled in 11 randomized trials and 24,509 in 15 non randomized trials). A total of 10,052 patients underwent radial approach and 19,142 patients underwent femoral approach. A total of 2499 patients (8.6%) had died at follow-up. Radial approach was associated with a significant reduction in short-term mortality (5.2% vs 10.3%, OR [95% CI]=0.55 [0.40, 0.76], p<0.001, p het=0.97) (primary endpoint). Significant benefits were observed in both randomized (2.7% vs 4.7%, OR [95% CI]=0.55 [0.40, 0.76], p<0.001, p het=0.97) and observational studies (5.9% vs 11.1%, OR [95% CI]=0.48 [0.43, 0.54, p<0.001, p het=0.44]). Major bleeding complications were observed in a total of 808 patients (2.8%). Radial approach was associated with a significant reduction in major bleeding complications as compared to femoral approach (1.9% vs 4.7%, OR [95% CI]=0.38 [0.31, 0.47], p<0.0001, p het=0.17), similarly in both randomized (2.7% vs 5%, OR [95% CI]=0.51 [0.37, 0.70], p<0.001, p het=0.87) and observational studies (1.4% vs 4.6%, OR [95% CI]=0.32 [0.25, 0.42], p<0.0001, p het=0.32). Both benefits in death and major bleeding complications were not related to baseline risk profile., Conclusions: This meta-analysis of randomized and non-randomized trials showed that among STEMI patients undergoing primary angioplasty the radial approach is associated with a consistent reduction in mortality and major bleeding complications and. Therefore, routine use of radial approach should be strongly encouraged in primary angioplasty., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Several studies have found that among patients with ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, female sex is associated with a worse outcome. However, still controversial is the prognostic impact of gender in primary angioplasty, especially in the era of drug-eluting stents (DES). Therefore, the aim of this study was to investigate sex-related differences in clinical outcome in patients with STEMI treated with primary angioplasty with Bare-Metal Stent (BMS) or DES., Methods: Our population is represented by 6298 STEMI patients undergoing primary angioplasty and stent implantation included in the DESERT database. Follow-up data were collected from 3 to 6 years after primary angioplasty., Results: Female gender was observed in 1466 (23.2%) out of 6298 STEMI patients. Women were older (65.3 ± 12.4 vs 59.3 ± 11.4 years, p < 0.001), with higher prevalence of diabetes (18.6% vs 14.5%, p < 0.001), hypertension (52.4% vs 41.4%, p < 0.001), slightly longer ischemia time (272 ± 247 vs 258 ± 220 min, p = 0.06). No difference was observed in terms of angiographic and procedural characteristics. Follow-up data were available at a mean of 1201 ± 441 days. At long-term follow-up female gender was associated with a significantly higher rate of death (11.7% vs 8.5%, HR [95% CI] = 1.45 [1.18-1.78], p < 0.001), while no difference was observed in terms of reinfarction (HR [95% CI] = 1.14 [0.89-1.45], p = 0.3), ST (HR [95% CI] = 1.12 [0.85-1.48], p = 0.4), with similar temporal distribution (acute, subacute, late and very late) between male and female patients, and no difference in TVR (HR [95% CI] = 1.11 [0.95-1.3], p = 0.2, p = 0.2). These results were confirmed in both patients receiving BMS or DES. The impact of female gender on mortality disappeared after correction for baseline confounding factors (HR [95% CI] = 0.88 [0.71-1.09], p = 0.25)., Conclusions: This study shows that in patients with STEMI treated by primary angioplasty, female gender is associated with higher mortality rate in comparison with men, and this is mainly due to their higher clinical and angiographic risk profiles. In fact, female sex did not emerge as an independent predictor of mortality., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Despite mechanical reperfusion, elderly patients with ST-segment elevation myocardial infarction (STEMI) still experience unsatisfactory outcomes. Drug-eluting stents (DES) have significantly reduced target-vessel revascularization (TVR), but concerns have emerged about the higher risk of late stent thrombosis, which may be more pronounced in elderly patients. Therefore, the aim of this study was to evaluate the impact of age on outcome in patients with STEMI who underwent primary angioplasty with bare-metal stents (BMS) or DES. Our population comprised 6,298 patients who underwent primary angioplasty and stent implantation included in the Drug-Eluting Stent in Primary Angioplasty (DESERT) Cooperation database. Age was significantly associated with female gender (p <0.001), diabetes (p <0.001), hypertension (p <0.001), previous myocardial infarction (MI; p <0.001), ischemia time (p <0.001), and anterior MI (p <0.001) but inversely related to smoking (p <0.001). Elderly patients most often had infarct-related artery located in the descending artery (p = 0.014) and impaired postprocedural thrombolysis in myocardial infarction flow (p <0.001). Elderly patients were less often on clopidogrel at follow-up. At long-term follow-up, age was associated with a higher rate of death (hazard ratio [95% confidence interval] = 2.17 [1.97 to 2.39], p <0.0001), whereas no impact was observed on reinfarction (p = 0.36), stent thrombosis (p = 0.84), and TVR (p = 0.54). These results were confirmed in patients receiving both BMS and DES. The impact of age on mortality was confirmed after correction for baseline confounding factors (gender, diabetes hypertension, hypercholesterolemia, smoking, ischemia time, anterior MI, infarct-related artery location, and postprocedural thrombolysis in myocardial infarction 3 flow; adjusted hazard ratio [95% confidence interval] = 2.13 [1.78 to 2.56], p <0.001). In conclusion, this study shows that in patients with STEMI who underwent primary angioplasty, age is independently associated with higher mortality, observed with both BMS and DES, whereas no impact was observed on the rate of reinfarction, stent thrombosis, and TVR., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: Even though primary angioplasty restores TIMI 3 flow in more than 90% of STEMI patients, the results in terms of myocardial perfusion are still unsatisfactory in a relatively large proportion of patients. Great interest has been focused in the last years on distal embolization as major determinant of poor reperfusion and clinical outcome after primary angioplasty. The aim of this article is to perform an updated meta-analysis of thrombectomy devices in STEMI patients undergoing primary angioplasty., Methods: The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to December 2010, the scientific session abstracts (from January 1990 to December 2010) and oral presentation and/or expert slide presentations (from January 2002 to December 2010) (on TCT, AHA, ESC, ACC and EuroPCR websites). No language restrictions were enforced., Results: A total of 21 randomized trials were finally included in the meta-analysis, involving 4514 patients (2270 or 50.3% randomized to thrombectomy and 2244 or 49.7% to standard angioplasty). Overall thrombectomy did not reduce 30-day mortality, with more benefits observed only with manual thrombectomy. No difference was observed in the 30-day reinfarction rate, whereas a trend in higher risk of stroke was observed with thrombectomy (p=0.06). Manual but not mechanical thrombectomy significantly improved postprocedural TIMI 3 flow, however, both devices significantly improved myocardial reperfusion as evaluated by ST-segment resolution. By meta-regression analysis a linear relationship was observed between benefits from thrombectomy in ST-segment resolution and in the presence of thrombus at baseline angiography (p=0.0016)., Conclusions: The present meta-analysis has demonstrated that, among patients with STEMI, manual thrombectomy significantly improved myocardial perfusion, with a trend in short-term mortality benefits, whereas mechanical thrombectomy, despite the benefits in myocardial perfusion, did not impact on short-term survival. However, the benefits in myocardial perfusion were significantly related to prevalence of coronary thrombus. In light of the observed higher risk of stroke, thrombectomy cannot be routinely recommended, but should be used in case of evident intracoronary thrombus. Mechanical thrombectomy devices may be considered as well to further improve reperfusion and facilitate optimal stent implantation, especially in the presence of large thrombus burden., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Glycoprotein IIb-IIIa (Gp IIb-IIIa), a fibrinogen receptor located on platelet surface, is a key point in the pathway leading to platelet aggregation. Therefore, great interest has emerged in the last decades on its pharmacological block, both by irreversible binding of abciximab or by competitive small molecules (tirofiban and eptifibatide). Gp IIb-IIIa inhibitors, in fact have demonstrated to provide benefits in clinical outcome among patients with acute myocardial infarction and in complex elective percutaneous coronary intervention (PCI) procedures. Still unclear is whether the genetic Leu 33Pro substitution in Gp IIIa may affect the extent of platelet aggregation inhibition by these drugs. Therefore, the aim was to evaluate whether this polymorphism (PlA) may influence inhibition of platelet aggregation after Gp IIb-IIIa administration in patients undergoing coronary angioplasty. We analyzed 80 patients undergoing nonurgent coronary revascularization and receiving Gp IIb-IIIa inhibitors (bolus and endovenous infusion; 40 patients with Abciximab and 40 patients with eptifibatide or tirofiban). The aggregation tests were performed at baseline and after 10 min, 1 h and 4 h, through multiplate impedance aggregometry. The PlA polymorphic variant was found in 26 patients (32.5%). The PlA carriers did not differ significantly from wild-type subjects for main clinical and angiographic features, except for in-stent restenosis that was more frequent among PlA carriers (P = 0.003). Therapy and aggregation values at baseline were similar in the two groups. The Leu33Pro substitution did not influence platelet response after Gp IIb-IIIa administration, which was confirmed for both abciximab and small molecules. This study showed that Leu33Pro polymorphism of Gp IIIa does not affect the extent of inhibition of platelet aggregation by Gp IIb-IIIa inhibitors.

Background: Myocardial necrosis is a time-dependent event. Nevertheless, clinical studies on association between ischemic time and left ventricle function showed inconsistent findings. Aim of current study is to evaluate the association between ischemic time and the post-infarction left ventricular function in ST-elevation myocardial infarction treated with primary PCI., Methods: In 2529 patients treated with primary PCI, left ventricular ejection fraction (LVEF) was measured before discharge (median day 4) by radionuclide ventriculography or by echocardiography if patients had atrial fibrillation. Ischemic time was calculated from symptom onset to first balloon inflation., Results: The correlation between ischemic time as continuous variable and LVEF was significant but weak (P=0.002, r=-0.062). The LVEF of patients in ischemic time intervals of >6, >3-6, and ≤3 h was 45.1±11.7%, 44.6±11.9%, and 43.2±12.2%, respectively (P=0.029). Adjusted odds ratio of the ischemic time intervals for LVEF<40% was 1.14 (95% CI 1.00-1.30). TIMI flow 0 before and TIMI flow 3 after PCI were related with both longer ischemic time and low LVEF., Conclusion: Ischemic time was associated with post infarction LVEF in patients treated with primary PCI, although this association was weak. Initial TIMI flow and post-PCI TIMI flow played important role in impact of the ischemic time on the LVEF., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Several concerns have emerged regarding the higher risk for stent thrombosis (ST) after drug-eluting stent (DES) implantation, especially in the setting of ST-segment elevation myocardial infarction (STEMI). Few data have been reported so far in patients with diabetes mellitus, which is associated with high rates of target vessel revascularization after bare-metal stent (BMS) implantation but also higher rates of ST after DES implantation. Therefore, the aim of this study was to perform a meta-analysis of individual patients' data to evaluate the long-term safety and effectiveness of DES compared with BMS in patients with diabetes who undergo primary percutaneous coronary intervention for STEMI. Published reports were scanned by formal searches of electronic databases (MEDLINE and CENTRAL). All completed randomized trials of DES for STEMI were examined. No language restrictions were enforced. Individual patients' data were obtained from 11 of 13 trials, including a total of 972 patients with diabetes (616 [63.4%] randomized to DES and 356 [36.6%] to BMS). At long-term follow-up (median 1,095 days, interquartile range 1,087 to 1,460), DES significantly reduced the occurrence of target vessel revascularization (hazard ratio 0.42, 95% confidence interval 0.29 to 0.59, p <0.0001), without any significant difference in terms of mortality, late reinfarction, and ST (>1 year) with DES. In conclusion, this meta-analysis, based on individual patients' data from 11 randomized trials, showed that among patients with diabetes with STEMIs who undergo primary percutaneous coronary intervention, sirolimus-eluting stents and paclitaxel-eluting stents, compared with BMS, are associated with a significant reduction in target vessel revascularization at long-term follow-up, without any apparent concern in terms of mortality, despite the trend toward higher rates of reinfarction and ST., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI). Mean platelet volume (MPV) has been proposed as a marker for platelet activation, as larger sized platelets have been associated with higher pro-thrombotic risk. Therefore, aim of the current study was to evaluate whether MPV is associated with increased risk of PMI after PCI., Methods: We included 1056 consecutive patients undergoing PCI. We measured myonecrosis biomarkers at intervals from 6 to 48 h after PCI. Periprocedural myonecrosis was defined for troponin I increase by 3 times the ULN or by 50% if elevated at the time of the procedure. PMI was defined as CK-MB increase by 3 times the ULN or 50% if elevated at the time of the procedure., Results: We grouped patients according to tertiles values of MPV (<10.4 fl; 10.5-11.3 fl; >11.4 fl). High MPV was associated with diabetes (p = 0.025) and higher prevalence of cerebrovascular events (p = 0.005). MPV significantly related with haemoglobin levels (p < 0.001), but inversely to platelet count (p < 0.001) and higher presence of thrombus (p = 0.03). Larger sized platelets did not increase risk of periprocedural myonecrosis (p = 0.91; OR[95% CI] = 1.04[0.90-1.2], p = 0.64) or PMI (p = 0.09; OR[95%IC] = 1.13[0.93-1.37]; p = 0.20). Subgroup analysis confirmed no impact of MPV on periprocedural MI also in high-risk subsets of patients, such as those with ACS at presentation (OR[95%CI] = 1.09 [0.87-1.38]; p = 0.44), diabetes (OR[95% CI] = 1.02[0.71-1.47], p = 0.91), female gender (OR [95% CI] = 1.15 [0.78-1.71], p = 0.48), elderly patients (age ≥ 75 years) (OR[95%CI] = 1.21[0.87-1.69], p = 0.25) or with renal failure (OR[95%CI] = 1.55[0.91-2.61], p = 0.1)., Conclusions: This study demonstrates that MPV does not predict the risk of PMI in patients undergoing PCI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Diabetes has been shown to be associated with worse survival and repeat target vessel revascularization (TVR) after primary angioplasty. The aim of the current study was to evaluate the impact of diabetes on long-term outcome in patients undergoing primary angioplasty treated with bare metal stents (BMS) and drug-eluting stents (DES)., Research Design and Methods: Our population is represented by 6,298 ST-segment elevation myocardial infarction (STEMI) patients undergoing primary angioplasty included in the DESERT database from 11 randomized trials comparing DES with BMS., Results: Diabetes was observed in 972 patients (15.4%) who were older (P < 0.001), more likely to be female (P < 0.001), with higher prevalence of hypertension (P < 0.001), hypercholesterolemia (P < 0.001), and longer ischemia time (P < 0.001), and without any difference in angiographic and procedural characteristics. At long-term follow-up (1,201 ± 441 days), diabetes was associated with higher rates of death (19.1% vs. 7.4%; P < 0.0001), reinfarction (10.4% vs. 7.5%; P < 0.001), stent thrombosis (7.6% vs. 4.8%; P = 0.002) with similar temporal distribution--acute, subacute, late, and very late--between diabetic and control patients, and TVR (18.6% vs. 15.1%; P = 0.006). These results were confirmed in patients receiving BMS or DES, except for TVR, there being no difference observed between diabetic and nondiabetic patients treated with DES. The impact of diabetes on outcome was confirmed after correction for baseline confounding factors (mortality, P < 0.001; repeat myocardial infarction, P = 0.006; stent thrombosis, P = 0.007; TVR, P = 0.027)., Conclusions: This study shows that among STEMI patients undergoing primary angioplasty, diabetes is associated with worse long-term mortality, reinfarction, and stent thrombosis in patients receiving DES and BMS. DES implantation, however, does mitigate the known deleterious effect of diabetes on TVR after BMS.

Background: Adjunctive abciximab administration has been demonstrated to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over IV route. Therefore, the aim of the current study was to perform a meta-analysis of randomized trials (RCTs) to assess the clinical efficacy and safety of IC vs IV abciximab administration in STEMI patients undergoing primary angioplasty., Methods: We obtained results from all RCTs enrolling STEMI patients undergoing primary percutaneous coronary intervention (PCI). The primary endpoint was mortality, while recurrent myocardial infarction, postprocedural epicardial (TIMI 3) and myocardial (MBG 2-3) perfusion were identified as secondary endpoints. The safety endpoint was the risk of major bleeding complications., Results: A total of 8 randomized trials were finally included in the meta-analysis, enrolling a total of 3259 patients. As compared to IV route, IC abciximab was associated with a significant improvement in myocardial perfusion (OR [95% CI]=1.76 [1.28-2.42], p<0.001), without significant benefits in terms of mortality (OR [95% CI]=0.85 [0.59-1.23], p=0.39), reinfarction (OR [95% CI]=0.79 [0.46-1.33], p=0.37), or major bleeding complications (OR [95% CI]=1.19 [0.76-1.87], p=0.44). However, we observed a significant relationship between patient's risk profile and mortality benefits from IC abciximab administration (p=0.011)., Conclusions: The present updated meta-analysis showed that IC administration of abciximab is associated with significant benefits in myocardial perfusion, but not in clinical outcome at short-term follow-up as compared to IV abciximab administration, without any excess of major bleedings in STEMI patients undergoing primary PCI. However, a significant relationship was observed between patient's risk profile and mortality benefits from IC abciximab administration. Therefore, waiting for long-term follow-up results and additional randomized trials, IC abciximab administration cannot be routinely recommended, but may be considered in high-risk patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Concerns have emerged regarding a higher risk of stent thrombosis after drug-eluting stent (DES) implantation, especially in the setting of ST-segment elevation myocardial infarction (STEMI). Our objective was to perform a meta-analysis using individual patient data to evaluate the long-term safety and effectiveness of DES compared with bare-metal stents (BMS) in patients undergoing primary percutaneous coronary intervention for STEMI., Data Sources: Formal searches of electronic databases (MEDLINE and CENTRAL) and scientific session presentations from January 2000 to June 2011., Study Selection: We examined all completed randomized trials of DES for STEMI., Data Extraction: Individual patient data., Data Synthesis: Individual patient data were obtained from 11 of 13 trials identified, including a total of 6298 patients (3980 [63.2%] randomized to DES [99% sirolimus-eluting or paclitaxel-eluting stents] and 2318 [36.8%] randomized to BMS). At long-term follow-up (mean [SD], 1201 [440] days), DES implantation significantly reduced the occurrence of target-vessel revascularization (12.7% vs 20.1%; hazard ratio [95% CI], 0.57 [0.50-0.66]; P < .001, P value for heterogeneity, .20), without any significant difference in terms of mortality, reinfarction, and stent thrombosis. However, DES implantation was associated with an increased risk of very late stent thrombosis and reinfarction., Conclusions: The present pooled patient-level meta-analysis demonstrates that among patients with STEMI undergoing primary percutaneous coronary intervention, sirolimus-eluting and paclitaxel-eluting stents compared with BMS are associated with a significant reduction in target-vessel revascularization at long-term follow-up. Although there were no differences in cumulative mortality, reinfarction, or stent thrombosis, the incidence of very late reinfarction and stent thrombosis was increased with these DES.

Objective: Although most patients with ST-elevation myocardial infarction treated by primary percutaneous coronary intervention (PCI) have a good prognosis and can be discharged from hospital very soon, some patients must be admitted longer. We performed the current analysis to assess predictors and the prognostic significance of prolonged hospital stay., Patients and Methods: In this prospective observational study, individual data from 2323 patients who survived at least 2 days after primary PCI in our hospital were recorded. Patients in the highest tertile of hospital stay were compared with the other patients. Both predictors and prognostic importance of prolonged hospital stay were evaluated., Results: Mean admission duration was 6.7 days (standard deviation=6.6). A total of 797 patients had a hospital stay for more than 6 days (highest tertile). Patients with a longer hospital stay were older, more often female, had more often a history of previous myocardial infarction and signs of heart failure on admission, and had more frequently Thrombolysis in Myocardial Infarction flow 0 before PCI. In addition, a low left ventricular ejection fraction was independently associated with prolonged hospital stay [odds ratio: 2.06 (95% confidence interval: 1.54-2.76)], but with a comparable risk of 1-year mortality [odds ratio: 1.3 (95% confidence interval: 0.8-2.0)]., Conclusion: According to this study, a low left ventricular ejection fraction is associated with prolonged hospital stay in patients after primary PCI. Predictors of prolonged hospital stay are age, female sex, previous myocardial infarction, heart failure on admission, and Thrombolysis in Myocardial Infarction flow 0 before PCI.

This is a prospective, observational study performed in all consecutive ST-elevation myocardial infarction (STEMI) patients who had activated clotting time (ACT) measurement on arrival in the cathlab before coronary angiography. We studied the therapeutic effects of a pre-hospital fixed heparin bolus dose in consecutive patients with STEMI. A total of 1,533 patients received pre-hospital administration of aspirin, high dose clopidogrel (600 mg) and a fixed bolus dose of 5,000 IU unfractionated heparin (UFH), according to the national ambulance protocols. Some patients were also treated with glycoprotein IIb/IIIa inhibitors (GPI) in the ambulance. A therapeutic ACT range was defined according to the ESC guidelines as 200-250 seconds when patients had GPI pre-treatment and 250-350 seconds when no GPI pre-treatment. Of the 1,533 patients, 216 patients (14.1%) had an ACT within the therapeutic range, 82.3% of the patients had a too low ACT, whereas 3.5% of the patients had a too high ACT. After multivariable analysis, the only independent predictor of a too low ACT was increasing weight (odds ratio 1.02/kg, 95% confidence interval 1.01-1.03, p=0.001). Patients with a too low ACT had less often an open infarct related vessel (initial TIMI flow 2,3) as compared to patients with an ACT in range (36.5% vs. 45.9%, p=0.013). In only a minority of patients with STEMI, pre-hospital treatment with a fixed bolus dose UFH is within the therapeutic ACT range. Increased weight is an independent determinant of a too low ACT. We strongly recommend weight adjusted administration of UFH in the ambulance.

Purpose: Grade 3 ischemia (G3I: distortion of the terminal portion of the QRS complex) is a predictor of serious complications after acute myocardial infarction. However, less is known about which patients are more prone to present with G3I., Methods: Patients who were enrolled in the Ongoing Tirofiban In Myocardial infarction Evaluation trial 2 were included. These patients were divided in 2 groups based on the enrolment electrocardiogram: grade 2 ischemia (G2I) or G3I., Results: Between June 2004 and November 2007, 1308 patients with interpretable electrocardiograms were enrolled. Grade 3 ischemia was found in 426 (32.6%) patients. Patients with G3I were older, more often male, more often had diabetes, had a Thrombolysis In Myocardial Infarction (TIMI) risk score of greater than 3, had 3 vessel disease, had an anterior infarction, more often presented in Killip class greater than 1, less often had a preprocedural TIMI 3 flow, and less often had a myocardial blush grade 3 post-PCI. One hour post-PCI, residual ST deviation was higher in patients with G3I compared with patients with G2I. Furthermore, G3I was associated with more major cardiac events (including death, myocardial infarction, urgent target vessel revascularization). After multivariate adjustment, G3I was an independent predictor of failure of ST-segment resolution 1 hour post-PCI (odds ratio, 1.4; 95% confidence interval, 1.1-1.9) and 30-day mortality (odds ratio, 3.2; 95% confidence interval, 1.2-8.7)., Conclusion: Grade 3 ischemia was associated with high-risk patient criteria (older age, diabetes, TIMI risk score >3, Killip class >1, and anterior myocardial infarction) and represents a subgroup of high-risk patients who seems to be associated with poor myocardial reperfusion and worse outcome., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Primary Percutaneous Intervention (PCI) is the treatment of choice for acute ST-elevation myocardial infarction (STEMI). Nearly half of STEMI patients have multivessel (MV) disease that has been associated with worse survival. However, current guidelines recommend to treat only the culprit artery (COR) during the acute procedure. Thus, the aim of the current study was to perform a meta-analysis of trials comparing MV PCI vs. COR for STEMI patients with MV disease. Medline/CENTRAL and Web were searched for comparative studies (both randomized and non randomized trials) about MV PCI vs. COR for STEMI patients reporting mortality, re-PCI and re-MI data. Primary endpoint was 30-day mortality. The meta-analysis included 10 studies (2 randomized and 8 registries; N = 31224). As compared with COR, MV PCI significantly reduced long term rate of re-PCI (OR [95% CI] = 0.47 [0.28-0.78], P = 0.003) without increasing 30-day mortality (OR [95% CI] = 1.30 [0.79-2.12], P = 0.31) and long term re-MI (OR [95% CI] = 0.94 [0.43-2.06], P = 0.88). This meta-analysis showed safety and efficacy of MV PCI approach as compared with COR, with a significant reduction in rate of revascularizations, but no advantages in death and re-MI.

Background: We evaluated the effect of prehospital triage (PHT) in the ambulance on infarct size and clinical outcome and studied its relationship to the distance of patient's residence to the nearest percutaneous coronary intervention (PCI) center., Methods: All consecutive ST-segment elevation myocardial infarction patients who were transported to the Isala klinieken from 1998 to 2008 were registered in a dedicated database. Of these, 2,288 (45%) were referred via a spoke center and 2.840 (55%) via PHT., Results: PHT patients were more often treated within 3 hours after symptom onset (46.2% vs 26.8%, P < .001), more often had a post-procedural thrombolysis in myocardial infarction (TIMI) 3 flow (93.0% vs 89.7%, P < .001) had a smaller infarct size (peak creatine kinase 2,188 ± 2,187 vs 2,575 ± 2,259 IU/L, P < .001) and had a lower 1-year mortality (4.9% vs 7.0%, P = .002). After multivariate analysis, PHT was independently associated with ischemic time less than 3 hours (OR 2.45, 95% CI 2.13-2.83), a peak creatine kinase less than the median value (OR 1.19, 95% CI 1.04-1.36) and a lower 1-year mortality (OR 0.67, 95% CI 0.50-0.91). The observed differences between PHT patients and the spoke group were more pronounced in the subgroup of patients living >38 km from the PCI center., Conclusion: PHT in the ambulance is associated with a shorter time to treatment, a smaller infarct size and a more favorable clinical outcome, especially with longer distance from the patient's residence to the nearest PCI center. Therefore, PHT in the ambulance may reduce the negative effect of living at a longer distance from the PCI center., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: The objective of this study is to evaluate the incidence, predictors, and outcome of complete ST-segment resolution (STR) during transportation after pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2 trial., Methods: Patients with ST-segment elevation myocardial infarction were randomized in the ambulance to pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU unfractionated heparin. Complete STR was defined as ≥70% STR on the electrocardiogram obtained before percutaneous coronary intervention (PCI) as compared with the inclusion electrocardiogram., Results: Complete STR before PCI occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs 14.6%, P = .05). Independent predictors for complete STR before PCI were younger age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per 10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15-minute increase time from symptom onset to diagnosis), longer pretreatment time (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9, P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs 2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality., Conclusions: Dual or triple antiplatelet pretreatment in the ambulance results in complete STR before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction diagnosis, prehospital initiation of pretreatment early after symptom onset, and HDT independently predicted STR before PCI. Complete STR is associated with improved clinical outcome., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: We evaluated the Genous™ Bio-engineered R stent™ in elderly patients undergoing non-urgent percutaneous coronary intervention. The elderly have an increased risk of (temporary) discontinuation of clopidogrel, which is associated with a higher risk of developing stent thrombosis (ST)., Methods and Results: In the e-HEALING registry, 2,651 patients were <65, 1,403 were 65-74 and 869 were ≥ 75 years old. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related car-diac death or myocardial infarction and target vessel revascularization. Secondary outcomes included target lesion revascularization (TLR) and ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. TVF occurred significantly more often in elderly patients compared with younger patients (7.0% in patients aged < 65, 8.8% in patients aged 65-74 and 11.7% in patients aged ≥ 75 years, P<0.001). There was a trend to higher TLR with increasing age (log-rank P=0.06) and no difference in ST., Conclusions: The 1-year results of the Genous stent in a population of elderly patients show a significantly higher TVF rate compared with younger patients, mainly driven by a higher mortality. Although there was a trend to higher TLR rates with increasing age, there was no difference in ST. This attests to the safety of this therapy for the elderly, in whom there could be concerns with administering long-term dual antiplatelet therapy.

Aims: Although closure devices may be comfortable for patients, the clinical benefits in patients with moderate-to-high risk of bleeding are not yet clear. We compared a closure device with manual compression in moderate- to high-risk bleeding patients undergoing percutaneous coronary intervention (PCI)., Methods and Results: A randomized study was performed to compare a closure device (Angio-Seal, St. Jude Medical, Inc.) with manual compression in 627 patients treated with aspirin, clopidogrel, a glycoprotein IIb/IIIa inhibitor and heparin during PCI. The primary endpoint was the inhospital combined incidence of: 1) severe hematoma > 5 cm at the puncture site or groin bleeding resulting in prolonged hospital stay, transfusion and/or surgical intervention at the puncture site; 2) arteriovenous fistula formation and/or surgical intervention at the puncture site. A total of 313 patients (49.9%) were randomized to the closure device and 314 patients (50.1%) to manual compression. The combined primary endpoint was 2.6% in the closure device group compared to 4.5% in the manual compression group (p = 0.195). In the predefined subgroup of patients with a history of hypertension, however, the combined primary endpoint (0.8% vs. 7.2%; p = 0.008) was significantly reduced after use of the closure device., Conclusion: This trial did not show the superiority of using a closure device over manual compression in patients treated with triple antiplatelet therapy who underwent PCI. The fact that patients with a history of hypertension had a benefit from a closure device merits further investigation.

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated whether presentation of patients with STEMI to a noninterventional facility requiring transfer for primary PCI compared to direct admission to a PCI center has an impact on clinical outcomes. Of 3,602 patients enrolled in the multicenter, prospective HORIZONS-AMI trial, 988 (24.7%) were transferred for primary PCI and 2,614 were directly admitted to an interventional hospital. Clinical outcomes at 30 days and 1 year were evaluated. Median time to reperfusion in patients with transfer was 67 minutes longer compared to patients without transfer (272 vs 205 minutes, p <0.001), and first door-to-balloon time was 47 minutes longer (134 vs 87 minutes, p <0.001). At 30 days and 1 year there were no significant differences between patients with and without transfer in the rates of major adverse cardiac events (30 days 5.8% vs 5.4%, p = 0.68; 1 year 11.6% vs 12.0%, p = 0.74), major bleeding (30 days 7.3% vs 6.9%, p = 0.66; 1 year 7.9% vs 7.4%, p = 0.63), or mortality (30 days 2.6% vs 2.6%, p = 0.92; 1 year 4.0% vs 4.2%, p = 0.81). In transfer and nontransfer patients use of bivalirudin compared to unfractionated heparin plus glycoprotein IIb/IIIa inhibitor was associated with lower rates of bleeding, cardiac death, and net adverse clinical events. In conclusion, in the HORIZONS-AMI trial, 30-day and 1-year survival rates and clinical outcomes were comparable in patients with STEMI requiring and not requiring transfer for primary PCI., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Aims: Glycoprotein IIb/IIIa blocking agents seem to improve percutaneous coronary intervention (PCI) results in patients with ST-elevation myocardial infarction (STEMI). We aimed to compare the effect of pre-hospital administration of tirofiban in STEMI patients with and without diabetes mellitus (DM) treated with primary PCI., Methods and Results: We performed a pre-specified sub-analysis of the randomised On-Time II trial (n=984) and it's open label run-in phase (n=414), which investigated pre-hospital administration of high dose tirofiban in STEMI patients treated with primary PCI. Two-hundred and twenty (16%) diabetic patients (known DM or Hba1C ≥6.2%) were included, 101 in the placebo group and 119 in the tirofiban group. In patients with DM, randomisation to tirofiban resulted in a lower residual ST deviation (5.1±8.5 mm vs. 6.2±5.6 mm, p=0.003), a reduced infarct size (CK 1694±1925 U/L vs. CK 2040±1829 U/L, p=0.02) and a trend towards lower one-year mortality (4.6% vs. 11.6%, p=0.07). The beneficial effects of tirofiban were more pronounced in diabetic patients compared to patients without diabetes., Conclusions: Pre-hospital administration of tirofiban in diabetic STEMI patients treated with primary PCI improves ST resolution and reduces myocardial infarct size. Tirofiban seems particularly beneficial in patients with diabetes.

Objectives: To assess the influence of age as an independent factor determining the prognosis and outcome of patients with acute myocardial infarction (AMI) treated using primary percutaneous coronary intervention (PCI)., Design: A retrospective analysis from a dedicated database., Setting: A high-volume interventional cardiology center in the Netherlands., Participants: Four thousand nine hundred thirty-three consecutive patients with AMI., Measurements: Baseline characteristics and clinical outcomes after 30 days and 1 year were compared according to age categorized in three groups: younger than 65, 65 to 74, and 75 and older. A more-detailed analysis was performed with six age groups, from younger than 40 to 80 and older., Results: Of the 4,933 consecutive patients with AMI treated with PCI between 1992 and 2004, 643 were aged 75 and older. Multivariate analysis revealed that patients aged 65 to 75 had a greater risk of 1-year mortality than those younger than 65 (adjusted odds ratio (AOR)=1.57, 95% confidence interval (CI)=1.15-2.16) and that those aged 75 and older had a greater risk of 1-year mortality than those younger than 65 (AOR=3.03, 95% CI=2.14-4.29)., Conclusion: In this retrospective analysis, older age was independently associated with greater mortality after PCI for AMI. Patients aged 65 and older had a higher risk of mortality than younger patients, and those aged 75 and older had the highest risk of mortality.

Aims: To investigate incidence, predictors and prognosis of bleeding in ST elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI)., Methods and Results: A large scale, prospective, observational study was performed between 1991 and 2004 in a single teaching hospital in The Netherlands including all consecutive STEMI patients who underwent primary PCI. The independent association between both major and minor bleeding and one year mortality was evaluated using Cox proportional hazard models. A total of 5,030 patients were included, of whom 109 patients (2%) had cardiac surgery within 48 hours. Data on bleeding <48 hours were available in 4,717 patients (96%). Of these, 80 (1.6%) had major bleeding, whereas minor bleeding was observed in 266 patients (5.6%). Independent predictors of minor bleeding were advanced age, multivessel disease, Killip class > or = 2 on admission, anterior MI location and TIMI 0 flow before PCI. Killip class > or = 2 on admission was an independent predictor of major bleeding. Major bleeding (HR 3.5 [95% CI 2.3-5.4]) was associated with an increased risk of death at one year., Conclusions: After primary PCI, the incidence of major bleeding is less than 2%. Although relatively infrequent, major bleeding complications are strongly and independently related to short- and midterm mortality.

Importance of the Field: Inhibition of platelet aggregation plays a key role in treatment of coronary artery disease., Areas Covered in This Review: Studies on the effects of tirofiban in patients with either ST elevation or non-ST elevation myocardial infarction are reviewed., What the Reader Will Gain: Tirofiban is a small-molecule glycoprotein IIb/IIIa receptor inhibitor. If discontinued, the action of tirofiban is faster reversed as abciximab. The dose varied between low (bolus of 0.4 microg/kg administered over 30 min followed by an infusion of 0.10 microg/kg/min), intermediate (bolus of 10 microg/kg administered over 3 min followed by an infusion of 0.15 microg/kg/min) and high (bolus of 25 microg/kg administered over 3 min followed by an infusion of 0.15 microg/kg/min). The high-dose administration especially may be beneficial in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). There is no indication for tirofiban in patients treated with thrombolysis. Patients with non-ST elevation myocardial infarction requiring PCI are most likely to benefit from tirofiban if they have ongoing ischemia and/or dynamic ECG changes. The risk of serious bleeding with tirofiban is low and there is a very low risk of thrombocytopenia., Take Home Message: Use of tirofiban for myocardial infarction is effective and has an acceptable safety profile.