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Objective: To evaluate changes in residual platelet reactivity (RPR) over time, and bleeding and ischaemic events rate using 5 vs 10 mg maintenance dose (MD) regimens of prasugrel 1 month after acute coronary syndrome (ACS)., Background: The optimal level of RPR with prasugrel may change over time after an ACS., Methods: After 60 mg loading dose of prasugrel (T0) followed by 10 mg/day for 1 month, patients were randomised to receive prasugrel 10 mg/day (n=95, group A) or 5 mg/day MD (n=98, group B) up to 1 year. RPR was assessed at T0, 37 (T1) and 180 days (T2). The primary end point was Bleeding Academic Research Consortium (BARC) bleeding events ≥2 between 1 and 12 months, and the secondary composite end point was cardiac death, myocardial infarction, stroke and definite/probable stent thrombosis., Results: From T0 to T1, RPR significantly increased in both groups A and B and the increase was higher for group B (δ ADP 10 µmol: 13.8%±14.7% vs 23.5%±19.2%, p=0.001). At T2 a lower rate of high RPR patients were found in group A (2.6% vs13.3%; p=0.014). The BARC type ≥2 bleeding occurred in 12.6% of group A versus 4.1% of group B (OR 0.29, 95% CI 0.09 to 0.94) and secondary end point in 2.1% vs 1.0% (p=0.542), respectively, without stent thrombosis., Conclusions: RPR increases shifting from 60 mg loading dose to 10 mg/day prasugrel MD with a further increase of RPR reducing prasugrel MD to 5 mg 1 month after ACS. Clinical value of these pharmacodynamic findings should be proved in larger clinical trials., Trial Registration Number: NCT01790854., Competing Interests: GP reported receiving consulting fee from: AstraZeneca, Eli Lilly, The Medicines Company and Bayer. RM reported receiving honoraria for lectures from Daiichi Sankyo/Eli Lilly and Merck Sharp & Dohme. RA reported receiving consulting fees from Eli Lilly; lecture fees from Instrumentation Laboratory and Sigma Tau; and research grant funding from Bayer, BoehringerIngelheim and Pfizer. GFG reported receiving consulting fees from Bayer, BoehringerIngelheim and Eli Lilly; lecture fees from AstraZeneca, GlaxoSmithKline, Instrumentation Laboratory, Menarini and Sigma Tau; and research grant funding from Novo Nordisk, Merck Sharp & Dohme, Pfizer, Pierrel, Sanofi-Aventis and Servier. DA reported receiving consulting fees from Daiichi Sankyo/Eli Lilly and The Medicines Company and serving on the advisory boards of Cordis and CID.

Objectives: We sought to analyze whether rheolytic thrombectomy (RT) in comparison with manual thrombus aspiration (MTA) may reduce microvascular obstruction (MVO), infarct size (IS), and left ventricular (LV) remodeling in ST-elevation myocardial infarction (STEMI)., Background: Conflicting results have been reported as to whether MTA reduces MVO and IS., Methods and Results: Eighty STEMI reperfused by primary angioplasty and abciximab were randomly allocated (1:1) to RT or MTA. Cardiac magnetic resonance imaging (MRI) was performed in 37 patients (19 RT) and after 1 year in 19 (9 RT); baseline, 1- and 6-month 2D-echo was performed in all patients. MVO and IS were measured 8 min after gadolinium injection with late enhancement sequences and were analyzed quantitatively at a core laboratory blinded to randomization. At baseline TIMI thrombus grade were similar (RT: 4.47 ± 0.84 vs. MTA: 4.67 ± 0.76, P = 0.453). After thrombectomy, thrombus grade decreased to 1.11 ± 1.04 in RT vs. 2.17 ± 1.29 in MTA arm (P = 0.009). RT compared with MTA did not reduced significantly myocardial IS [12.2% (6.4-22.1) vs. 19.0% (7-28.5), P = 0.224] as well as the extent of MVO [0.0% (0.0-0.17) vs. 0.6% (0.0-1.4), P = 0.117], but a trend toward a lower incidence of MVO (16% vs. 44%, P = 0.056) and a less LV remodeling rate were found in RT arm (11% vs. 24%, P < 0.140)., Conclusion: RT in comparison with MTA was more effective in thrombus removal, but it did not reduced significantly the IS and the extent of MVO. However, a trend toward a lower incidence of MVO and a better preservation of LV volumes were found in RT arm. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: The study sought to determine the impact of high residual platelet reactivity (HRPR) on long-term cardiac mortality in diabetic patients treated with PCI for CTO. No data exist about the impact of HRPR after 600 mg clopidogrel loading on long-term clinical outcome in patients with diabetes mellitus and treated with percutaneous coronary angioplasty (PCI) for chronic total occlusion (CTO)., Methods: From the Florence CTO-PCI registry, we identified consecutive diabetic patients with available in vitro platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel. HRPR was defined as residual platelet aggregation by 10 μmol/L ADP test ≥70%. The primary end point of the study was long-term cardiac mortality., Results: Two-hundred and three diabetic patients underwent CTO-PCI. The incidence of HRPR was 23%. The 3-year cardiac survival was lower in the HRPR group than the low residual platelet reactivity (LRPR) group (70 ± 7% and 92 ± 3%, respectively; p=0.001). Within the oral antidiabetic patients there were no significant differences in long-term survival between HRPR and LRPR groups. Conversely, the association of insulin therapy and HRPR was related to a dramatic decrease in survival compared to the LRPR group (34 ± 14% vs. 89 ± 4%; p<0.001). At multivariable analysis insulin therapy (HR 4.31; p=0.001) and HRPR (HR 3.26; p=0.004) were significantly related to long-term mortality, while completeness of revascularization was inversely related to cardiac mortality (HR 0.40; p=0.029)., Conclusion: HRPR is a strong marker of increased risk of cardiac death in patients with DM who underwent PCI for CTO., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to investigate the efficacy of prasugrel compared with clopidogrel in clopidogrel nonresponders., Background: Clopidogrel nonresponsiveness is a strong marker of the risk of cardiac death and stent thrombosis after a percutaneous coronary intervention (PCI). It is unknown whether clopidogrel nonresponsiveness is a nonmodifiable risk factor or whether prasugrel with more potent and predictable platelet inhibition as measured by ex vivo techniques is associated with a positive effect on clinical outcome., Methods: The RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt thrombosis) study screened clopidogrel nonresponders after a 600-mg loading dose of clopidogrel. Clopidogrel nonresponders switched to prasugrel (10 mg/day) the day of the PCI, and an adenosine diphosphate (ADP) test (10 μmol/l of ADP) was performed 6 days after the PCI. The primary endpoint was 2-year cardiac mortality. Patient outcome was compared with the RECLOSE-2-ACS study., Results: We screened 1,550 patients, of whom 302 were clopidogrel nonresponders. The result of the ADP test was 77.6 ± 6.2%. After switching to prasugrel, the ADP test result decreased to 47.1 ± 16.8%. The 2-year cardiac mortality rate was 4% in the RECLOSE-3 study and 9.7% in nonresponders of the RECLOSE-2-ACS study (p = 0.007). The definite and probable stent thrombosis rates were 0.7% and 4.4%, respectively (p = 0.004). On multivariable analysis, prasugrel treatment was related to the risk of 2-year cardiac death (hazard ratio: 0.32, p = 0.036)., Conclusions: Clopidogrel nonresponsiveness can be overcome by prasugrel (10 mg/day), and optimal platelet aggregation inhibition on prasugrel treatment is associated with a low rate of long-term cardiac mortality and stent thrombosis., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In acute coronary syndrome (ACS) patients older than 75 years old, prasugrel 10 mg maintenance therapy has shown less clinical efficacy and higher risk of bleeding. In patients older than 75 years, a prasugrel dose of 5 mg should be used if treatment is deemed necessary., Objective: The aim of this study was to compare platelet reactivity and outcomes in elderly patients receiving prasugrel 5mg therapy with non-elderly patients receiving prasugrel 10 mg therapy., Methods and Results: Consecutive ACS patients undergoing percutaneous coronary intervention (PCI) treated with prasugrel were included. Of 718 patients, 228 (32%) had ≥75 years and received prasugrel 5 mg/day. Residual platelet reactivity (RPR) was 47±18% and 36±16% in the elderly and non-elderly group, respectively (p=0.001). High RPR (≥70%) was found in 9% and 2% (p=0.0001) in elderly and non-elderly patients, respectively. In the 6-month follow-up, there was no difference in mortality, stent thrombosis, and reinfarction rates between the 2 groups but a higher rate of TIMI minor bleeding (7.9% vs 2.4%; p=0.001) in elderly as compared with younger patients. Age≥75 years was independently associated with bleeding events (HR 2.162 [1.105-4.229]; p=0.024)., Conclusions: Elderly patients receiving prasugrel 5mg are more likely to experience high RPR than younger patients treated by prasugrel 10 mg. Despite the use of a reduced prasugrel maintenance dose and a higher level of RPR, elderly patients show increased risk of bleeding during prasugrel therapy as compared to younger patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

There are very few clinical data concerning the safety of switching from clopidogrel to prasugrel in patients undergoing coronary stenting. However, in the daily activity, clinicians face the decision of switching patients at high-risk of thrombotic events from clopidogrel to prasugrel. Thus, we sought to evaluate clinical events in patients undergoing coronary stent implantation and prasugrel therapy with (SWITCH group) or without (NAÏVE group) prior clopidogrel therapy. A total of 454 patients with stable or unstable coronary artery disease, aged 70 ± 10 years, underwent non-emergent stent implantation and received prasugrel therapy. Of these, 315 (69 %) patients received clopidogrel before switching to prasugrel therapy. In 239 patients with high residual platelet reactivity (HRPR) on clopidogrel, prasugrel decreased platelet aggregation from 72 ± 11 to 43 ± 16 % (p < 0.001). There was no difference in in-hospital major or minor TIMI bleeding (2.8 vs. 4.3 %; p = 0.411) between the SWITCH and NAÏVE groups as well as in mortality, acute stent thrombosis, reinfarction and stroke rates. At multivariable analysis, independent predictors of bleeding were female gender (OR 5.56 [1.41-19.88] p = 0.014) and chronic renal failure (OR 6.27 [1.59-21.65] p = 0.009), but switching therapy did not. This result was confirmed after switching propensity score adjustment (c-statistic 0.81; Hosmer-Lemeshow test p = 860). Switching from clopidogrel to prasugrel in patients undergoing non-emergent coronary stent implantation seems to be tolerated with no overt signs of increased bleeding.

Background: Although primary angioplasty achieves Thrombolysis In Myocardial Infarction (TIMI) 3 flow in most patients with ST-elevation myocardial infarction, epicardial recanalization does not guarantee optimal perfusion in a large proportion of patients. Multivessel disease has been demonstrated to be associated with impaired survival, however its impact on infarct size has not been largely investigated, that therefore is the aim of the current study., Methods: Our population is represented by 827 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi., Results: Multivessel disease was observed in 343 patients (41.5%). It was associated with older age (65 [57-74] vs 63 [53-71], p < 0.001), higher rate of previous MI (6.4% vs 2.5%, p = 0.005), longer ischemia time evaluated as continuous variable (210 [155-280] min vs 196 [145-270] min, p = 0.065) or percentage of patients with ischemia time >3 h (63.7% vs 56.4%, p = 0.038), and a trend in more cardiogenic shock (5.5% vs 2.9%, p = 0.055). Patients with multivessel disease received more often Abciximab (92.1% vs 88.4%, p < 0.001), Intra-aortic balloon pump (6.4% vs 1.9%, p < 0.001). No differences were observed in other clinical or angiographic characteristics. In particular, multivessel disease did not affect the rate of postprocedural TIMI 3 flow (90.9% vs 93.4%, p = 0.18) and ST-segment resolution (52.4% vs 54.9%, p = 0.48). Multivessel disease did not affect infarct size (12.7% [4.5%-24.9%] vs 12.3% [4%-24.1%], p = 0.58). Similar results were observed in subanalyses without any significant interaction for each variable (anterior infarct location (p int = 0.23), gender (p int = 0.9), age (p int = 0.7), diabetes (p int = 0.15)). The absence of any impact of multivessel disease on infarct size was confirmed when the analysis was conducted according to the percentage of patients with infarct size above the median, even after correction for baseline characteristics, such as age, previous MI, ischemia time, use of Gp IIb-IIIa inhibitors, cardiogenic shock, ischemia time (OR [95% CI] = 1.09 [0.82-1.45], p = 0.58)., Conclusions: This study shows that among STEMI patients undergoing primary PCI multivessel disease does not affect infarct size., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Prior studies have found that smokers with STEMI have lower mortality rates and a more favorable response to fibrinolytic therapy than nonsmokers, phenomenon defined as "the smoker's paradox". Still poorly explored is the impact of cigarette smoking in patients undergoing primary percutaneous coronary intervention. Aim of the current study was to evaluate the impact of cigarette smoking on scintigraphic infarct size in STEMI patients undergoing primary PCI., Methods: Our population is represented by 830 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi., Results: Smoking was associated with younger age (p < 0.001), a lower prevalence of female gender (p < 0.001), hypertension (p < 0.001), diabetes (p = 0.003), shorter ischemia time (p = 0.037), but higher rates of previous PCI (p = 0.016). No differences were observed in other clinical or angiographic characteristics. In particular, smoking did not affect the rate of postprocedural TIMI 3 flow. As shown in Fig. 1, smoking did not affect infarct size (12.5% [3.3%-23.7%] vs 12.7% [4.9%-25.9%], p = 0.12). Similar results were observed in subanalyses according to infarct location (anterior STEMI, p int = 0.33), gender (p int = 0.95) age, (p Int = 0.96), diabetes (p int = 0.85). The absence of any impact of smoking on infarct size was confirmed after correction for baseline characteristics, such as age, gender, hypertension, diabetes, previous PCI, ischemia time (OR [95% CI] = 0.80 [0.59-1.09], p = 0.15)., Conclusions: This study shows that among STEMI patients undergoing primary PCI smoking status does not affect infarct size., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Hypertension is a well known risk factor for atherosclerosis. However, data on the impact of hypertension in patients with ST-segment elevation myocardial infarction (STEMI) are inconsistent, and mainly related to studies performed in the thrombolytic era, with very few data on patients undergoing primary angioplasty. The aim of the current study was to evaluate the impact of hypertension on scintigraphic infarct size in STEMI patients undergoing primary percutaneous coronary intervention (PCI)., Method: Our population is represented by 830 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi., Results: Hypertension was associated with more advanced age (P<0.001), a larger prevalence of diabetes (P=0.001), female sex (P<0.001), but lower prevalence of smoking (P<0.001) and anterior infarction (P=0.042). No difference was observed in ischemia time, cardiogenic shock at presentation, in preprocedural thrombolysis in myocardial infarction (TIMI) flow, and collateral circulation. Hypertension did not affect the rate of postprocedural TIMI 3 flow. Hypertension did not affect infarct size [12.5% (4.1-23.8%) vs. 12.8% (4.3-24.7%), P=0.38]. Similar results were observed in subanalyses in major high-risk subgroups. No impact of hypertension on infarct size was confirmed when the analysis was conducted according to the percentage of patients with infarct size above the median [adjusted odds ratio (95% CI)=0.97 (0.72-1.33), P=0.92]., Conclusion: This study shows that among STEMI patients, undergoing primary PCI hypertension does not affect scintigraphic infarct size.

Objectives: This study sought to compare the action of prasugrel and ticagrelor in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI)., Background: It has been documented that prasugrel and ticagrelor are able to provide effective platelet inhibition 2 h after a loading dose (LD). However, the pharmacodynamic measurements after prasugrel and ticagrelor LD have been provided by assessing only healthy volunteers or subjects with stable coronary artery disease., Methods: Fifty patients with STEMI undergoing PPCI with bivalirudin monotherapy were randomized to receive 60 mg prasugrel LD (n = 25) or 180 mg ticagrelor LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 2, 4, 8, and 12 h after LD., Results: Platelet reactivity units (PRU) 2 h after the LD (study primary endpoint) were 217 (12 to 279) and 275 (88 to 305) in the prasugrel and ticagrelor groups, respectively (p = NS), satisfying pre-specified noninferiority criteria. High residual platelet reactivity (HRPR) (PRU ≥240) was found in 44% and 60% of patients (p = 0.258) at 2 h. The mean time to achieve a PRU <240 was 3 ± 2 h and 5 ± 4 h in the prasugrel and ticagrelor groups, respectively. The independent predictors of HRPR at 2 h were morphine use (odds ratio: 5.29; 95% confidence interval: 1.44 to 19.49; p = 0.012) and baseline PRU value (odds ratio: 1.014; 95% confidence interval: 1.00 to 1.03; p = 0.046)., Conclusions: In patients with STEMI, prasugrel showed to be noninferior as compared with ticagrelor in terms of residual platelet reactivity 2 h after the LD. The 2 drugs provide an effective platelet inhibition 2 h after the LD in only a half of patients, and at least 4 h are required to achieve an effective platelet inhibition in the majority of patients. Morphine use is associated with a delayed activity of these agents. (Rapid Activity of Platelet Inhibitor Drugs Study, NCT01510171)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Several clinical studies have demonstrated that anginal attacks shortly before the onset of STEMI limit infarct size and improve short- and long-term outcomes. However, the clinical significance of preinfarction angina in STEMI patients treated by primary PCI is still controversial. Therefore, the aim of the current study was to evaluate the impact of preinfarction angina on scintigraphic infarct size in STEMI patients undergoing primary PCI., Methods: Our population is represented by 430 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi., Results: Preinfarction angina was associated with more advanced age, a larger prevalence of family history for CAD, smoking, and longer ischemia time. No difference was observed in other clinical or angiographic characteristics. Preinfarction angina did not affect either the rate of postprocedural TIMI 3 flow or infarct size (19 ± 15.5 vs 16 ± 13.9, p = 0.18). Similar results were observed in subanalyses according to infarct location (anterior STEMI: 22.7 ± 14.8 vs 19.2 ± 16.1, p = 0.36; non-anterior STEMI: 16.1 ± 15.7 vs 13.8 ± 11.6, p = 0.36), gender (female gender: 15.6 ± 14.5 vs 11.5 ± 13.2, p = 0.30; male gender 20.4 ± 16 vs 17.2 ± 13.8, p = 0.3) or ischemia time (≤ or > 4 h) (17.6 ± 15.6 vs 15.8 ± 14.1, p = 0.52; 21.6 ± 15.5 vs 16.7 ± 13.3, p = 0.18). The absence of any impact of preinfarction angina on infarct size was confirmed after correction for baseline characteristics, such as age, smoking, family history for CAD and ischemia time (OR [95% CI] = 1.26 [0.66-2.41], p = 0.48)., Conclusions: This study shows that among STEMI patients undergoing primary PCI preinfarction angina does not affect infarct size., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)