Consensus Document ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: Long-term Antiplatelet Therapy in Patients with Coronary Artery Disease.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be difficult to identify the ideal patient profile which could safely reduce or prolong the DAPT duration in daily clinical practice. The aim of this consensus document is to review contemporary literature on optimal DAPT duration, and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial).

AIMS: AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. METHODS: Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. RESULTS: Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months-treatment effect vs. CONTROL: +1.24 mL/kg/min (95% confidence interval 0.26-2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). CONCLUSION: Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. TRIAL REGISTRATION NUMBER: NCT01311791.

[ANMCO/ANCE/ARCA/GICR-IACPR intersociety consensus document: long-term antiplatelet therapy in patients with coronary artery disease]. / Documento di consenso intersocietario ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: La terapia antiaggregante a lungo termine nel paziente con malattia coronarica.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of the pharmacologic management of patients with acute coronary syndrome (ACS) and/or receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischemia, repeat hospitalization, and death. Over the last years, multiple randomized clinical trials have been published comparing duration of DAPT after PCI and in ACS patients investigating either a shorter or prolonged DAPT regimen.Although current European Society of Cardiology guidelines provide backup to individualize treatment, it seems difficult to identify the ideal patient profile who could safely reduce or prolong DAPT duration in daily clinical practice. The aim of this consensus document is to review the contemporary literature on optimal DAPT duration and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure.

AIMS: AUGMENT-HF was an international, multicentre, prospective, open-label, randomized, controlled evaluation testing the hypothesis that Algisyl (injectable calcium alginate hydrogel) is superior to standard medical therapy (SMT) for improving functional capacity and clinical outcomes in patients with advanced heart failure (HF). We previously reported results following 6 months of follow-up. This report presents the results from 1 year of extended follow up for this clinical trial. METHODS AND RESULTS: We enrolled 78 patients with advanced HF, randomized (1:1), to Algisyl with SMT or SMT alone as previously reported. Patient inclusion criteria were LVEF ≤35%, peak VO2 of 9.0-14.5 mL/min/kg and LV end-diastolic diameter (LVEDD) index 30-40 mm/m(2) (LVEDD/body surface area). Patients must have been on stable, evidence-based therapy for HF. A total of 58 patients, mean age 62.3 ± 9.6 years, with ischaemic (57.7%) or non-ischaemic (42.3%) HF completed 12 months of follow-up. Treatment with Algisyl was associated with improved peak VO2 at 12 months; treatment effect vs. control of +2.10 mL/kg/min (95% confidence interval 0.96-3.24, P < 0.001). Statistically significant improvements were observed for VO2 at anaerobic threshold, 6-min walk test distance, and NYHA functional class (all P < 0.001). Through 12 months of follow-up there were 4 (10.5%) deaths in the control group and 9 (22.5%) deaths in the Algisyl group. CONCLUSIONS: Algisyl in addition to SMT was more effective than SMT alone for providing sustained 1-year benefits in exercise capacity, symptoms, and clinical status for patients with advanced HF. These data support larger clinical evaluations of this novel therapy.

Failure of gamma-hydroxybutyric acid both to increase neuroactive steroid concentrations in adrenalectomized-orchiectomized rats and to induce tolerance to its steroidogenic effect in intact animals.

Gamma-Hydroxybutyric acid (GHB), a drug proposed in the treatment of alcohol withdrawal syndrome, increases the cerebrocortical and plasma concentrations of the neuroactive steroids allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC). In the present study, we examined the role of hypothalamic-pituitary-adrenal (HPA) axis in the effect of GHB by measuring the concentrations of these steroids in the brain and plasma of adrenalectomized-orchiectomized (Adx-Orx) rats. The acute administration of GHB (500 mg/kg, i.p.) induced in 30 min an increase in the concentrations of allopregnanolone, THDOC and their precursors pregnenolone and progesterone in different brain areas (cerebral cortex, hypothalamus and cerebellum) and plasma of sham-operated rats but had no effect on the concentrations of these compounds in Adx-Orx rats, suggesting that activation of the HPA axis mediates the effect of GHB on brain and plasma concentrations of neuroactive steroids. Moreover, we evaluated whether repeated exposure of GHB induces tolerance to its steroidogenic effects. Chronic administration of GHB (500 mg/kg, i.p., twice a day for 10 days) to intact animals failed to affect the levels of progesterone, allopregnanolone, or THDOC measured 3 or 48 h after the last drug administration, whereas a challenge injection of GHB or ethanol was still able to increase the concentrations of these steroids in brain and plasma. These results indicate that repeated exposure to GHB fails to induce tolerance or cross-tolerance to the steroidogenic action of GHB or ethanol, respectively.