Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Outcomes of Left Main Revascularization after Percutaneous Intervention or Bypass Surgery.

Background: This study is aimed at comparing the clinical outcomes of unprotected left main coronary artery disease (ULMCAD) treatment with contemporary percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in a "real-world" population. Methods and Results: Overall, 558 consecutive patients with ULMCAD (mean age 71 ± 9 years, male gender 81%) undergoing PCI or CABG were compared. The primary endpoint was the composite of death, nonfatal myocardial infarction, or stroke. Diabetes was present in 29% and acute coronary syndrome in 56%; mean EuroSCORE was 11 ± 8. High coronary complexity (SYNTAX score >32) was present in 50% of patients. The primary composite endpoint was similar after PCI and CABG up to 4 years (15.5 ± 3.1% vs. 17.1 ± 2.6%; p=0.585). The primary end point was also comparable in a two propensity score matched cohorts. Ischemia-driven revascularization was more frequently needed in PCI than in CABG (5.5% vs. 1.5%; p=0.010). By multivariate analysis, diabetes mellitus (HR 2.00; p=0.003) and EuroSCORE (HR 3.71; p < 0.001) were the only independent predictors associated with long-term outcome. Conclusions: In a "real-world" population with ULMCAD, a contemporary revascularization strategy by PCI or CABG showed similar long-term clinical outcome regardless of the coronary complexity.

"Tailored" antiplatelet bridging therapy with cangrelor: moving toward personalized medicine.

In the setting of patients with indication to receive dual antiplatelet therapy undergoing surgery or invasive procedures, the risk of perioperative cardiac ischemic events, particularly stent thrombosis, is high, because surgery has a prothrombotic effect and antiplatelet therapy is withdrawn in order to avoid bleeding complications. Cangrelor, an intravenous P2Y12 receptor antagonist, has been tested in a randomized trial as a "bridge" to cardiac surgery from discontinuation of oral P2Y12 receptor antagonists. Thus, a consensus document extended its off-label use in this setting and before non-cardiac surgery. Currently, despite the implementation of a standardized bridging protocol with cangrelor, a residual risk of adverse outcome mainly due to bleeding events, still persist during the perioperative phase.Accordingly, a personalized management driven by platelet reactivity serial measurements and careful assessment of ischemic and bleeding risks has potential to optimize outcomes and costs as compared to a standardized bridging protocol, based on average pharmacodynamic data of oral P2Y12 inhibitors.While specific indications for bridging have been extensively addressed in the aforementioned consensus statement, the aim of the present document is the proposal of a "tailored" clinical decision-making algorithm inspired to the principle of personalized medicine dealing with complex clinical scenarios.

Transcatheter Aortic Valve Implantation in Younger Patients: A New Challenge.

The number of aortic stenosis patients in Western countries is increasing, along with better life conditions and expectancies. Presently, the volume of percutaneous transcatheter aortic valve implantations (TAVIs) is incessantly increasing, and has already overcome the surgical replacement procedure volume. According to the literature, TAVI is a feasible procedure even among low surgical risk patients, and American guidelines have extended the indications for TAVI, including shifting patient evaluations from high/low STS scores to old/young patients, a "paradigm shift" of aortic stenosis evaluation. As a result, low-risk young (<75 years-old) population management could be the next challenge in cardiology. To manage the life conditions of a 65 year old patient affected by aortic stenosis who is undergoing TAVI, one of the most crucial issue will be bioprosthesis durability and the appropriate intervention to make in cases of valve dysfunction or failure.

Impact of complete percutaneous revascularization in elderly patients with chronic total occlusion.

OBJECTIVE: The aim of the study was to assess the prognostic impact of successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and completeness of revascularization in the elderly. BACKGROUND: Successful CTO-PCI is associated with clinical benefit. Notwithstanding elderly patients are currently underrepresented in CTO-PCI randomized controlled trials and registries. METHODS: From the Florence CTO-PCI registry 1,405 patients underwent CTO-PCI between 2004 and 2015; out of these, 460 consecutive patients were ≥75 years. End point of the study was long-term cardiac survival. The prognostic impact of successful CTO-PCI and complete revascularization on survival was assessed by Kaplan-Meier estimation and by Cox multivariable regression analysis. RESULTS: Patients were stratified according to success (72%) or failure of CTO-PCI. Completeness of revascularization was achieved in 57% of patients. Five-year cardiac survival was significantly higher in the successful CTO-PCI group (84 ± 3% vs. 72 ± 6%; p = .006) and it was further improved if complete coronary revascularization was achieved (90 ± 3% vs. 68 ± 5%; p < .001). At multivariable analysis, increasing age (hazard ratio [HR] 1.08; p = .001), diabetes (HR 1.55; p = .033), chronic kidney disease (HR 1.96, p = .002), left ventricular ejection fraction <0.40 (HR 2.10; p < .001), and completeness of revascularization (HR 0.58; p < .005) resulted independently associated with long-term cardiac survival. CONCLUSIONS: In the elderly successful CTO-PCI is associated with a long-term survival benefit. The results of this study suggest that, even in the elderly, a CTO-PCI attempt should be considered to achieve complete coronary revascularization.

Antithrombotic therapy in acute coronary syndrome: undertreatment of elderly?

The appropriate use of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS) is largely debated. Due to the "demographic transition" in western countries, the elderly represent a growing percentage of patients admitted to hospitals for ACS, and among this high risk setting population most of early and late adverse outcomes occur. The presence of several concomitant "comorbidities" complicate the management strategy of both medical or invasive treatment and the clinical decision making process is challenging. Moreover, elderly people are constantly underrepresented in clinical trials and studies. As a result, there is no specific evidence about the optimal antithrombotic therapy in elderly and no specific recommendations are mentioned in the current ACS guidelines. Currently, the best practice for old people is still rudimentary and principally extrapolated from general cardiovascular guidelines. The management of elderly patients should be based on the evaluation of ischemic and hemorrhagic risk, life expectancy, comorbidities and parameters that are not included in the scores recommended by the current guidelines such as frailty and disability. In the era of "precision medicine", the evaluation of bleeding and ischaemic risk in elderly patients must be a dynamic process because of the risk changing over time. A"tailored therapy by individualized medicine" is the key of management strategy.

On-Treatment Platelet Reactivity is a Predictor of Adverse Events in Peripheral Artery Disease Patients Undergoing Percutaneous Angioplasty.

OBJECTIVES: Few data are available on the association between a different entity of platelet inhibition on antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). The aim of this study was to evaluate the degree of on-treatment platelet reactivity, and its association with ischaemic and haemorrhagic adverse events at follow up in PAD patients undergoing percutaneous transluminal angioplasty (PTA). METHODS: In this observational, prospective, single centre study, 177 consecutive patients with PAD undergoing PTA were enrolled, and treated with dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. Platelet function was assessed on blood samples obtained within 24 h from PTA by light transmission aggregometry (LTA) using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists of platelet aggregation. High on-treatment platelet reactivity (HPR) was defined by LTA ≥ 20% if induced by AA, and LTA ≥ 70% if induced by ADP. Follow up was performed to record outcomes (death, major amputation, target vessel re-intervention, acute myocardial infarction and/or myocardial revascularisation, stroke/TIA, and bleeding). RESULTS: HPR by AA and HPR by ADP were found in 45% and 32% of patients, respectively. During follow up (median duration 23 months) 23 deaths (13%) were recorded; 27 patients (17.5%) underwent target limb revascularisation (TLR), two (1.3%) amputation, and six (3.9%) myocardial revascularisation. Twenty-four patients (15.6%) experienced minor bleeding. On multivariable analysis, HPR by AA and HPR by ADP were independent predictors of death [HR 3.8 (1.2-11.7), p = .023 and HR 4.8 (1.6-14.5), p = .006, respectively]. The median value of LTA by ADP was significantly lower in patients with bleeding complications than in those without [26.5% (22-39.2) vs. 62% (44.5-74), p < .001). LTA by ADP ≤ 41% was independently associated with bleeding HR 14.6 (2.6-24.0), p = .001] on multivariable analysis. CONCLUSIONS: In this study a high prevalence of on-clopidogrel and aspirin high platelet reactivity was found, which was significantly associated with the risk of death. Conversely, a low on-clopidogrel platelet reactivity was associated with a higher risk of bleeding. These results document that the entity of platelet inhibition is associated with both thrombotic and bleeding complications in PAD patients.

Angiographic and clinical outcome after crush of everolimus-eluting stent for distal unprotected left main disease.

Obiectives: Angiographic and clinical outcomes after crushing of everolimus-eluting stent (EES) for distal unprotected left main disease (ULMD). BACKGROUND: Few data exist about crushing of EES for distal ULMD. METHODS: From the Florence ULMD Percutaneous Coronary Interevention Registry consecutive patients with distal ULMD treated with EES were included in the analysis. Patients treated with provisional stenting were compared with patients treated with crush stenting. ENDPOINTS: angiographic in-segment restenosis rate, and 1-year clinical outcome. RESULTS: From 2008 to 2015, 405 patients with distal ULMD were treated with EES: 278 (69%) were treated with provisional stenting while 127 (31%) with crush stenting. Provisional stenting group compared to crush stenting group had higher incidence of acute coronary syndrome on admission (63% vs. 52%; P = 0.033) and of left ventricular ejection fraction ≤ 40% (36% vs. 23%; p= 0.008), while patients treated with crush stenting had more frequently diabetes mellitus (35% vs. 21%; P = 0.003) and 3-vessel coronary artery disease (46% vs. 29%; P < 0.001). Angiographic follow rate was 95%. Restenosis rates were similar: 7.1% in the crush stenting group and 5.8% in the provisional stenting group. There were no differences in 1-year clinical outcome between crush stenting group and provisional stenting group: major adverse cardiac events 11.1% and 11.2%, stent thrombosis 0.8% and 1.4%, respectively. CONCLUSION: Crush stenting using EES in patients with complex distal ULMD is associated with low rates of restenosis and adverse clinical events and could be considered as a valid double stenting technique in all patients with complex ULMD bifurcation lesions. © 2017 Wiley Periodicals, Inc.

Long-Term Primary Patency Rate After Nitinol Self-Expandable Stents Implantation in Long, Totally Occluded Femoropopliteal (TASC II C & D) Lesions.

BACKGROUND: Endovascular therapy for long femoropopliteal lesions using percutaneous transluminal balloon angioplasty or first-generation of peripheral stents has been associated with unacceptable one-year restenosis rates. However, with recent advances in equipment and techniques, a better primary patency rate is expected. This study was conducted to detect the long-term primary patency rate of nitinol self-expandable stents implanted in long, totally occluded femoropopliteal lesions TransAtlantic Inter-Society Census (TASC II type C & D), and determine the predictors of reocclusion or restenosis in the stented segments. METHODS: The demographics, clinical, anatomical, and procedural data of 213 patients with 240 de novo totally occluded femoropopliteal (TASC II type C & D) lesions treated with nitinol self-expandable stents were retrospectively analysed. Of these limbs, 159 (66.2%) presented with intermittent claudication, while 81 (33.8%) presented with critical limb ischaemia. The mean-time of follow-up was 36±22.6 months, (range: 6.3-106.2 months). Outcomes evaluated were, primary patency rate and predictors of reocclusion or restenosis in the stented segments. RESULTS: The mean age of the patients was 70.9±9.3 years, with male gender 66.2%. Mean pre-procedural ABI was 0.45±0.53. One-hundred-and-seventy-five (73%) lesions were TASC II type C, while 65 (27%) were type D lesions. The mean length of the lesions was 17.9±11.3mm. Procedure related complications occurred in 10 (4.1%) limbs. There was no periprocedural mortality. Reocclusion and restenosis were detected during follow-up in 45 and 30 limbs respectively, and all were re-treated by endovascular approach. None of the patients required major amputation. Primary patency rates were 81.4±1.1%, 77.7±1.9% and 74.4±2.8% at 12, 24, and 36 months respectively. Male gender, severe calcification, and TASC II D lesion were independent predictors for reocclusion, while predictors of restenosis were DM, smoking and TASC II D lesions. CONCLUSIONS: Treatment of long, totally occluded femoropopliteal (TASC II C & D) lesions with nitinol self-expandable stents is safe and is associated with highly acceptable long-term primary patency rates.

Rheolityc thrombectomy in acute myocardial infarction: Effect on microvascular obstruction, infarct size, and left ventricular remodeling.

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.

Effect of diabetes on scintigraphic infarct size in STEMI patients undergoing primary angioplasty.

BACKGROUND: It has been shown that among patients with ST-segment elevation myocardial infarction (STEMI), diabetes is associated with a significantly higher mortality, mainly because of impaired reperfusion. However, few data have been reported so far on infarct size as evaluated by well-refined techniques, such as nuclear imaging techniques. Therefore, the aim of the current study was to investigate the effect of diabetes in infarct size as evaluated by myocardial scintigraphy in a large cohort of STEMI patients undergoing primary PCI. METHODS: We included 830 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99 m-sestamibi. A logistic regression analysis was performed to determine the relation between diabetes and infarct size (as above the median) after correction for baseline confounding factors. RESULTS: A total of 115 (13.8%) out of 830 patients suffered from diabetes. Diabetic patients were older (p < 0.001), with larger prevalence of female gender (p = 0.006) and hypertension (p = 0.001) but were less often smokers (p = 0.003). Diabetic patients had more often preprocedural thrombolysis in myocardial infarction grade 3 flow (p = 0.034) and less complete ST-segment resolution (p = 0.009). No difference was observed in scintigraphic infarct size between diabetes and control patients (p = 0.6)), which was confirmed at multivariate analysis after correction for baseline confounding factors (Adjusted OR [95% CI] = 0.87 [0.57-1.31, p = 0.51). CONCLUSION: Our study showed that among STEMI patients undergoing primary angioplasty, diabetes did not affect infarct size as compared with non-diabetic patients.

Residual platelet reactivity to predict long-term clinical outcomes after clopidogrel loading in patients with acute coronary syndromes: comparison of different cutoff values by light transmission aggregometry from the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) study.

The aim of this study was the identification of the optimal cutoff value of high residual platelet reactivity (HRPR) assessed by light transmission aggregometry (LTA) in the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) patient cohort to discriminate patients with and without major adverse cardiac events (MACE) and cardiac death at 2 years. The RECLOSE 2-ACS study included 1,789 patients with ACS who underwent LTA after clopidogrel loading. A post hoc cutoff value for HRPR was defined with the ROC curve and the Youden index and compared with the protocol-defined cutoff of 70 %. By ROC analysis, 63 % resulted the optimal cutoff value to predict both MACE and cardiac death at 2 years follow-up. A significant sensitivity improvement for the ROC-based cutoff value was noted (p < 0.001), at the price of lower specificity and predictive accuracy. The latter were 81 % for MACE and 85 % for cardiac death with the 70 % cutoff, while the respective figures were 73 and 75 % with the 63 % cutoff. The areas under the curve were virtually identical with the 70 and 63 % cutoffs both for MACE (0.71) and cardiac death (0.79). A residual platelet reactivity cutoff of 70 % by LTA, compared to the ROC-based cutoff of 63 %, allows for the identification of a subset of patients at very high risk of adverse ischemic events, making LTA-ADP test more acceptable in clinical practice for the identification of subjects at risk than other platelet function assays with broader definitions of HRPR.

Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study.

UNLABELLED: In ST-elevation myocardial infarction (STEMI) patients, residual platelet reactivity soon after a loading dose (LD) of prasugrel or ticagrelor is higher than that reported for healthy volunteers or subjects with stable coronary artery disease; and the majority of primary percutaneous coronary intervention (PPCI) procedures with bivalirudin monotherapy are performed without proper platelet inhibition. However, ticagrelor LD is just the daily dose, whereas prasugrel LD is 6-fold the long-term daily dose. We hypothesized that an increased ticagrelor LD may result in a faster and more effective platelet inhibition as compared with the standard prasugrel LD. METHODS: Fifty patients with STEMI, pretreated with intravenous aspirin, undergoing PPCI were randomized to receive prasugrel 60-mg LD (n = 25) or ticagrelor 360-mg LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD. RESULTS: At the time of LD, 90% of enrolled patients had an aspirin reactivity unit value <550. P2Y12 reaction units 1 hour after the LD (study primary end point) were 236 (129-289) and 248 (115-304) in the prasugrel and ticagrelor group, respectively (P = .899). High residual platelet reactivity (P2Y12 reaction units ≥240) was found in 43% and 56% of patients (P = .386) at 1 hour and in 30% and 32% of patients (P = .907) at 2 hours, respectively. There was no significant difference in bleeding, arrhythmias, or dyspnea episodes in the 2 groups. CONCLUSIONS: In patients with STEMI undergoing PPCI, double (360 mg) ticagrelor LD failed to achieve a faster and more intense platelet inhibition as compared with the standard prasugrel LD. Intravenously administered aspirin allowed to achieve a very early inhibition of acid arachidonic pathway.

Effects of a timely therapy with doxycycline on the left ventricular remodeling according to the pre-procedural TIMI flow grade in patients with ST-elevation acute myocardial infarction.

Doxycycline has been demonstrated to reduced left ventricular (LV) remodeling, but its effect in patients with ST-elevation myocardial infarction (STEMI) and a baseline occluded [thrombolysis in myocardial infarction (TIMI) flow grade ≤1] infarct-related artery (IRA) is unknown. According to the baseline TIMI flow grade, 110 patients with a first STEMI were divided into 2 groups. Group 1: 77 patients with TIMI flow ≤1 (40 patients treated with doxycycline and 37 with standard therapy, respectively), and a Group 2: 33 patients with TIMI flow 2-3 (15 patients treated with doxycycline and 18 with standard therapy, respectively). The two randomized groups were well matched in baseline characteristics. A 2D-Echo was performed at baseline and at 6 months, together with a coronary angiography, for the remodeling and IRA patency assessment, respectively. The LV end-diastolic volume index (LVEDVi) decreased in Group 2 [-3 mL/m(2) (IQR: -12 to 4 mL/m(2))], and increased in Group 1 [6 mL/m(2) (IQR: -2 to 14 mL/m(2))], (p = 0.001). In Group 2, LVEDVi reduction was similar regardless of drug therapy, while in Group 1 the LVEDVi was smaller in patients treated with doxycycline as compared to control [3 mL/m(2) (IQR: -3 to 8 mL/m(2)) vs. 10 mL/m(2) (IQR: 1-27 mL/m(2)), p = 0.006]. A similar pattern was observed also for LV end-systolic volume and ejection fraction. In STEMI patients at higher risk, as those with a baseline TIMI flow grade ≤1, doxycycline reduces LV remodeling.

Preprocedural TIMI flow and infarct size in STEMI undergoing primary angioplasty.

Despite optimal epicardial recanalization, primary angioplasty for STEMI is still associated with suboptimal reperfusion in a relatively large proportion of patients. The aim the current study was to evaluate the impact of preprocedural TIMI flow on myocardial scintigraphic infarct size among STEMI undergoing primary angioplasty. Our population is represented by 793 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi. Poor preprocedural TIMI flow (TIMI 0-1) was observed in 645 patients (81.3%). Poor preprocedural TIMI flow was associated with more hypercholesterolemia (p = 0.012), and a trend in lower prevalence of diabetes (p = 0.081). Preprocedural TIMI flow significantly affected scintigraphic and enzymatic infarct size. Similar findings were observed in the analysis restricted to patients with postprocedural TIMI 3 flow. The impact of preprocedural TIMI flow on scintigraphic infarct size was confirmed when the analysis was performed according to the percentage of patients above the median (p < 0.001) and after adjustment for baseline confounding factors (Hypercholesterolemia and diabetes) [adjusted OR (95% CI) for pre preprocedural TIMI 3 flow = 0.59 (0.46-0.75), p < 0.001]. This study shows that among patients with STEMI undergoing primary angioplasty, poor preprocedural TIMI flow is independently associated with larger infarct size.

Switching from clopidogrel to prasugrel in patients having coronary stent implantation.

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.

The Value of a Coronary Computed Tomography Angiography plus Stress Cardiac Magnetic Resonance Imaging Strategy for the Evaluation of Patients with Chronic Coronary Syndrome.

Background: Noninvasive imaging methods, either anatomical or functional tests, serve as essential instruments for the appropriate management of patients with established or suspected coronary artery disease (CAD). We sought to evaluate the safety and efficacy of a coronary computed tomography angiography (CCTA) plus stress cardiac magnetic resonance imaging (S-CMR) strategy in patients with chronic coronary syndrome (CCS). Methods: Patients with suspected CCS showing intermediate coronary plaques (stenosis 30-70%) at CCTA underwent S-CMR. Patients with a positive S-CMR were referred to invasive coronary angiography (ICA) plus instantaneous wave-free ratio (iFR), and myocardial revascularization if recommended. All patients received guideline-directed medical therapy (GDMT), including high-dose statins, regardless of myocardial revascularization. The primary endpoint was a composite of death from cardiovascular causes, non-fatal myocardial infarction, and unplanned revascularization. Results: According to the results of CCTA, 62 patients showing intermediate coronary plaques underwent S-CMR, which was positive for a myocardial perfusion deficit in n = 17 (27%) and negative in n = 45 (73%) patients. According to the results of ICA plus iFR, revascularization was performed in 13 patients. No differences in the primary endpoint between the positive and negative S-CMR groups were observed at 1 year (1 [5.9%] vs. 1 [2.2%], p = 0.485) and after a median of 33.4 months (2 [11.8%] vs. 3 [6.7%]; p = 0.605). Conclusions: Our study suggests that a CCTA plus S-CMR strategy is effective for the evaluation of patients with suspicion of CCS at low-intermediate risk, and it may help to refine the selection of patients with intermediate coronary plaques at CCTA needing coronary revascularization.

Detection of infarct size safety threshold for left ventricular ejection fraction impairment in acute myocardial infarction successfully treated with primary percutaneous coronary intervention.

PURPOSE: In acute myocardial infarction (AMI) treated by primary percutaneous coronary intervention (PCI), there is a direct relationship between myocardial damage and consequent left ventricular (LV) functional impairment. It is however unclear whether there is a safety threshold below which infarct size does not significantly affect LV ejection fraction (EF). The aim of this study was to evaluate the relationship between infarct size and LVEF in AMI patients treated by successful PCI using a specific statistical approach to identify a possible safety threshold. METHODS: Among patients with recent AMI submitted to perfusion gated single photon emission computed tomography (SPECT) to define the infarct size, the data of 427 subjects with sizable infarct size were considered. The relationship between infarct size and LVEF was analysed using a simple segmented regression (SSR) model and an iterative algorithm based on robust least squares (RLS) for parameter estimation. RESULTS: The RLS algorithm detected two break points in the SSR model, set at infarct size values of 11.0 and 51.5 %. Because the slope coefficients of the two extreme segments of the regression line were not significant, by constraining such segments to zero slope in the SSR model, the lower break point was identified at infarct size = 8 % and the upper one at 45 %. CONCLUSION: Using a rigorous statistical approach, it is possible to demonstrate that below a threshold of 8 % the infarct size apparently does not affect the LVEF and therefore a safety threshold could be set at this value. Furthermore, the same analysis suggests that the relationship between infarct size and LVEF impairment is lost for an infarct size > 45 %.

Comparison of myocardial reperfusion between intracoronary versus intravenous cangrelor administration in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Myocardial reperfusion is the main target of treatment in patients with ST-segment elevation myocardial infarction (STEMI). The intracoronary administration of cangrelor bolus could favor a higher local drug concentration, favoring an earlier thrombotic resolution and a reduced distal micro-embolization. METHODS: Seventy-one patients undergoing primary percutaneous coronary intervention (PCI) for STEMI: 37 treated with intracoronary and 34 with intravenous bolus administration of cangrelor. The primary endpoint was ST-segment elevation resolution (STR) ≥ 50% after 30 min from the end of the PCI. Other explorative reperfusion indices investigated were: STR ≥ 50% at 24 hours, STR ≥ 70% at 30 min, Thrombolysis In Myocardial Infarction frame count and the QT dispersion. Moreover, acute and subacute stent thrombosis, bleeding events and 30-day mortality have been evaluated. RESULTS: More frequent STR ≥ 50% was observed in the intravenous cangrelor bolus group as compared to the intracoronary administration at 30 min (71.9% vs. 45.5%; p = 0.033), the difference was maintained 24 hours after PCI (87.1% vs. 63.6%; p = 0.030). STR ≥ 70% at 30 min was statistically more frequent in the intravenous bolus administration cohort (66.7% vs. 28.6% p = 0.02). At multivariable analysis, intravenous cangrelor administration was significantly related to STR ≥ 50% (odds ratio: 3.586; 95% confidence interval: 1.134-11.335; p = 0.030). The incidence of Bleeding Academic Research Consortium 3-5 bleedings was 15.5% and mortality was 4.2% without any significant difference between the two groups. CONCLUSIONS: In conclusion the results of the study do not show any advantages in the administration of intracoronary bolus of cangrelor in patients affected by STEMI and treated with primary PCI.