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Background Patients with diabetes mellitus (DM) and acute coronary syndromes have a greater level of platelet aggregation and a poor response to oral antiplatelet drugs. Clopidogrel is still widely used in clinical practice, despite the current evidence favoring ticagrelor and prasugrel. Aim The aim of this study was to investigate the determinants of clopidogrel use in the population of the multicenter prospective 'Acute Coronary Syndrome and Diabetes Registry' carried out during a 9-week period between March and May 2015 at 29 Hospitals. Patients and methods A total of 559 consecutive acute coronary syndrome patients [mean age: 68.7±11.3 years, 50% ST-elevation myocardial infarction (STEMI)], with 'known DM' (56%) or 'hyperglycemia' at admission, were included in the registry; 460 (85%) patients received a myocardial revascularization. Results At hospital discharge, dual antiplatelet therapy was prescribed to 88% of the patients (clopidogrel ticagrelor and prasugrel to 39, 38, and 23%, respectively). Differences in P2Y12 inhibitor administration were recorded on the basis of history of diabetes, age, and clinical presentation (unstable angina/non-STEMI vs. non-STEMI). On univariate analysis, age older than 75 years or more, known DM, peripheral artery disease, previous myocardial infarction, previous revascularization, complete revascularization, previous cerebrovascular event, creatinine clearance, unstable angina/non-STEMI at presentation, Global Registry of Acute Coronary Events Score, EuroSCORE, CRUSADE Bleeding Score, and oral anticoagulant therapy were significantly associated with clopidogrel choice at discharge. On multivariate analysis, only oral anticoagulant therapy and the CRUSADE Bleeding Score remained independent predictors of clopidogrel prescription. Conclusion In the present registry of a high-risk population, clopidogrel was the most used P2Y12 inhibitor at hospital discharge, confirming the 'paradox' to treat sicker patients with the less effective drug. Diabetic status, a marker of higher thrombotic risk, did not influence this choice; however, bleeding risk was taken into account.

Aim: To evaluate outcomes related to antiplatelet therapy in patients with ST-elevation myocardial infarction (STEMI) admitted to the San Gerardo Hospital in Monza, an extracorporeal membrane oxygenation (ECMO) reference center in the Monza-Brianza area. Methods: This retrospective study enrolled patients with STEMI hospitalized between 2013 and 2017. Results: This study included 653 patients (mean age: 67.5 years, 71% male). Across the study period, ticagrelor use showed consistent increases, from 22% of patients during 2013 to 85% in 2017. Cardiac arrest prehospitalization occurred in 100 patients (15.3%), either at home (n = 85, 13.0%) or during transfer (n = 15, 2.3%); 46 patients underwent ECMO for refractory cardiac arrest. Rates of 90-day survival (hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.3-4.4, P = .004) and ST resolution (odds ratio [OR]: 2.5, 95% CI: 1.6-4.1, P = .000) were higher with ticagrelor than with other antiplatelet agents. When analyzed by each agent, patients on ticagrelor had longer survival (HR: 0.4, 95% CI: 0.2-0.8, P = .008) than patients on clopidogrel and more frequent ST resolution than those on clopidogrel or prasugrel (OR: 0.4, 95% CI: 0.2-0.7, P = .002 and OR: 0.4, 95% CI: 0.2-0.7, P = .006). There was no difference in mortality between ticagrelor and prasugrel. Conclusions: Changes in the treatment of high-risk patients with STEMI over time are in line with changes in treatment guidelines. In these patients, ticagrelor is associated with significantly improved 90-day mortality compared with clopidogrel.

ObjectivesTo first explore in Italy appropriateness of indication, adherence to guideline recommendations and mode of selection for coronary revascularisation.DesignRetrospective, pilot study.Setting22 percutaneous coronary intervention (PCI)-performing hospitals (20 patients per site), 13 (59%) with on-site cardiac surgery.Participants440 patients who received PCI for stable coronary artery disease (CAD) or non-ST elevation acute coronary syndrome were independently selected in a 4:1 ratio with half diabetics.Primary and secondary outcome measuresProportion of patients who received appropriate PCI using validated appropriate use scores (ie, AUS≥7). Also, in patients with stable CAD, we examined adherence to the following European Society of Cardiology recommendations: (A) per cent of patients with complex coronary anatomy treated after heart team discussion; (B) per cent of fractional flow reserve-guided PCI for borderline stenoses in patients without documented ischaemia; (C) per cent of patients receiving guideline-directed medical therapy at the time of PCI as well as use of provocative test of ischaemia according to pretest probability (PTP) of CAD.ResultsOf the 401 mappable PCIs (91%), 38.7% (95% CI 33.9 to 43.6) were classified as appropriate, 47.6% (95% CI 42.7 to 52.6) as uncertain and 13.7% (95% CI 10.5% to 17.5%) as inappropriate. Median PTP in patients with stable CAD without known coronary anatomy was 69% (78% intermediate PTP, 22% high PTP). Ischaemia testing use was similar (p=0.71) in patients with intermediate (n=140, 63%) and with high PTP (n=40, 66%). In patients with stable CAD (n=352) guideline adherence to the three recommendations explored was: (A) 11%; (B) 25%; (C) 23%. AUS was higher in patients evaluated by the heart team as compared with patients who were not (7 (6.8) vs 5 (4.7); p=0.001).ConclusionsUse of heart team approaches and adherence to guideline recommendations on coronary revascularisation in a real-world setting is limited. This pilot study documents the feasibility of measuring appropriateness and guideline adherence in clinical practice and identifies substantial opportunities for quality improvement.Trial registration numberNCT02748603.

The aim of this study was to investigate the effects of A 1 and A 2 adenosine-receptor activation on the sympathetic nervous system. The effects on efferent renal nerve activity of selective A 1 (CCPA; 2-chloro-N-6-cyclopentyladenosine) and A 2 (2HE-NECA; 2-hexynyl-5'-N-ethylcarboxamidoadenosine) adenosine-receptor agonists were studied in anesthetized rats either with intact baroreflexes (intact rats) or with bilateral sinoaortic denervation and vagotomy (denervated rats). After a control period of 5 min, A 1 or A 2 agonist or vehicle were intravenously infused for 8 min in separate groups of intact or denervated rats, in which arterial pressure and heart rate were continuously recorded. CCPA (5.0 μg/kg/min) and 2HE-NECA (0.7 μg/kg/min) were selected to obtain comparable blood pressure changes over the period of observation. Arterial pressure significantly and equally decreased during the A 1 (-41 ± 8%), and A 3 (-35 ± 5%) agonist administration. Heart rate significantly decreased during A 1 agonist infusion, but it did not change during A 2 agonist administration. Bilateral sinoaortic denervation and vagotomy did not modify the hemodynamic responses to both drugs. The A 1 and A 2 administration caused a large and significant increase in efferent renal nerve activity (+66 ± 22% and +76 ± 15%, respectively), and this effect was entirely abolished in denervated rats. A linear relation with a significant negative slope between changes in arterial pressure and changes in neural discharge was observed for each treatment. The comparison of the regression slopes showed that the reflex increase of efferent sympathetic activity caused by the administration of both agonists was significantly smaller than the increment induced by equipotent hypotensive dose of sodium nitroprusside (10 μg/kg). These data show that the selective activation of A 1 and A 2 receptors elicits a reflex increase in efferent renal nerve activity. This neural activation is smaller as compared with the effect of equihypotensive doses of sodium nitroprusside, thus indicating a blunting effect of both adenosine agonists on baroreceptor sensitivity.

Objective To assess whether granulocyte colony-stimulating factor (G-CSF) treatment induces a sustained benefit on adverse remodelling in patients with large anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction after successful reperfusion. Methods The STEM-AMI Trial was a prospective, placebo-controlled, multicentre study. Sixty consecutive patients with a first anterior STEMI, who underwent primary percutaneous coronary intervention 2–12 h after symptom onset, with LV ejection fraction (LVEF) ≤45% measured by echocardiography within 12 h after successful revascularisation (TIMI flow score ≥2), were randomised 1:1 to G-CSF (5 µg/Kg body weight b.i.d . ) or placebo. Clinical events and Major Adverse Cardiac and Cerebrovascular Event (MACCE) were monitored, and LVEF, LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes, and infarct size were evaluated by MRI at the final 3-year follow-up. Results Fifty-four patients completed the study, of whom 35 with MRI. No significant differences were found in mortality and MACCE between G-CSF and placebo-treated groups. The 3-year infarct size was not different between groups, whereas LVEDV was significantly lower in G-CSF (n=20) than in placebo (n=15) patients (170.1±8.1 vs 197.2±8.9 mL, respectively; p=0.033 at analysis of covariance). A significant inverse correlation was detected in G-CSF patients between the number of circulating CD34 cells at 30 days after reperfusion and the 3-year absolute and indexed LVEDV (ρ=−0.71, 95% CI −0.90 to −0.30, and ρ=−0.62, −0.86 to −0.14, respectively), or their change over time (r=−0.59, −0.85 to −0.11, and r=−0.55, −0.83 to −0.06, respectively). Conclusions G-CSF therapy may be beneficial in attenuating ventricular remodelling subsequent to a large anterior STEMI in the long term. No differences have been detected in clinical outcome.

Aims The aim of this study was to assess the effect of granulocyte colony-stimulating factor (G-CSF) on left ventricular (LV) function and volumes in patients with anterior ST-elevation myocardial infarction (STEMI) and depressed LV ejection fraction (EF). Methods and results Sixty consecutive patients with anterior STEMI, undergoing primary angioplasty percutaneous coronary intervention (PCI), with symptom-to-reperfusion time of 2–12 h and EF ≤45% after PCI, were randomized to G-CSF 5 μg/kg b.i.d. subcutaneously (n = 24) or placebo (n = 25) for 5 days, starting

BACKGROUND Recent guidelines for the management of arterial hypertension have emphasized the importance of total cardiovascular risk for setting the blood pressure (BP) goal to be achieved and the intensity with which it should be pursued. DESIGN To assess the degree of BP control in hypertensives receiving long-term antihypertensive treatment according to the presence of major cardiovascular risk factors or diseases and the level of individual total cardiovascular risk, a large sample of general practitioners throughout Italy had to evaluate a random sample of their hypertensive patients. METHODS A clinical history was collected for each patient and BP was measured three times using a reliable automatic instrument. To stratify the cardiovascular risk we used the criteria suggested by the 1999 WHO-ISH guidelines. RESULTS Among the 1204 patients recruited (mean age 64.2 +/- 11.4 years, 663 females), only 399 patients (33.1%) had a BP lower than 140/90 mmHg. Except for male sex and previous myocardial infarction, the concomitant presence of major cardiovascular risk factors or diseases was never associated to a better control of hypertension. BP control was unrelated to individual overall cardiovascular risk: BP was < 140/90 mmHg respectively in 44.0, 37.7, 33.5 and 42.1% (P for trend = 0.54) of people aged less than 65 years with low, medium, high and very high risk and in 27.7, 25.9 and 27.1% (P for trend = 0.91) of people aged more than 65 years at medium, high and very high risk. CONCLUSIONS BP control in Italian hypertensives is still unsatisfactory, even in patients at high and very high cardiovascular risk.

1. Afferent nerve fibres sensitive to changes in the renal chemical environment have been found in the rat. To verify the existence of these fibres in the rabbit and their response pattern, afferent renal nerve activity was recorded during pelvic perfusions with NaCl solutions at different concentrations. 2. The experiments were carried out in 13 anaesthetized rabbits. Arterial pressure from a femoral catheter and afferent renal nerve activity from the distal stump of a cut renal nerve bundle were recorded. Three catheters were inserted into the renal pelvis to measure pelvic pressure, to allow pelvic perfusions at constant rates and to drain pelvic fluids. 3. After a control period, the pelvis was perfused with physiological saline (0.14 mol/l for 2 min), followed by one of a series of solutions containing increasing concentrations of NaCl (0.5, 0.75, 1.0 and 1.5 mol/l for 2 min). Pelvic perfusion was performed both at a low (0.2 ml/min) and a high (0.8 ml/min) flow rate for each solution tested. 4. In all animals arterial pressure was not modified during pelvic perfusions. Physiological saline did not change afferent renal nerve activity at the low perfusion rate, but it significantly increased afferent renal nerve activity and pelvic pressure at the high rate. Hypertonic NaCl solutions caused progressive increases in afferent renal nerve activity at both perfusion rates, and these effects were larger at the high perfusion rate. 5. These data demonstrate, in the rabbit, the existence of renal afferent nerves sensitive to discrete changes in pelvic ionic or osmotic concentration. The neural response is enhanced when renal mechano- and chemo-receptors are simultaneously activated.