Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Long-term clinical outcomes and cost-effectiveness analysis in multivessel percutaneous coronary interventions: Comparison of drug-eluting stents, bare-metal stents and a mixed approach in patients at high and low risk of repeat revascularisation

Aims: To evaluate the long-term effectiveness and cost-efficacy of drug-eluting stents (DES) in a real world setting of multivessel percutaneous coronary intervention (PCI). Methods and results: We evaluated the 2-year outcome of all multivessel PCI in de novo lesions enrolled in a prospective web-based multicentre registry from July 2003 to December 2006. Among the 2,898 eligible patients, 1,315 were treated with bare-metal stent (BMS) alone, 657 with DES alone, and 926 with both. At 2-years, use of DES was associated with a lower propensity score adjusted incidence of major adverse cardiac events (MACE), death and myocardial infarction, and target vessel revascularisation (TVR) compared with BMS but only in patients at high risk of TVR. No difference was apparent between "pure" DES and the mixed approach. The matched cost-effectiveness analysis revealed DES to be more costly and more effective with a reasonable incremental cost-efficacy ratio for any MACE avoided only in patients with a high risk of TVR and only in comparison with "pure" BMS patients. Conclusions: In this real-world multivessel PCI registry, the use of DES and a mixed approach were associated with a 2-year reduction of adverse clinical outcomes in comparison with BMS especially in patients with a high risk of TVR. DES were cost-effective only in patients at high risk of TVR. © Europa Edition 2010. All rights reserved

Comparison of 2-year clinical outcomes with sirolimus and paclitaxel-eluting stents for patients with diabetes: Results of the REgistro regionale AngiopLastiche Emilia-Romagna registry

Background: Long-term outcomes of percutaneous coronary interventions (PCI) with sirolimus-eluting stents (SES) compared to paclitaxel-eluting-stents (PES) in unselected diabetics in routine practice is still debated. Objective: This study compared the 2-year incidence of MACE (all-cause mortality, nonfatal myocardial infarction and target vessel revascularization) of SES and PES in a real-world setting of patients with diabetes. Design: Observational, multicenter, nonrandomized study. Setting: Prospective web-based registry (REAL Registry; study period, 2002-2005) comprising all 13 hospitals performing PCI. Patients: Among the 945 eligible patients treated with either SES alone (n = 606) or PES alone (n = 339), 29% were insulin-requiring, 72% had multivessel coronary disease, 26% had prior myocardial infarction and 10% had poor left ventricular function. Measurements: Unadjusted and propensity score-adjusted 2-year clinical outcome. Results: After propensity score adjustment, 2-year MACE incidence in the SES and PES groups was equivalent (23.3% vs. 23.7%, HR 1.01, 95%CI 0.72-1.42, P = 0.96). Adjusted 2-year angiographic stent thrombosis occurred in 1.1% of the SES patients versus 2.6% of the PES patients (P = 0.15). In this large, real-world, diabetic population treated with DES, there was no difference in outcome between SES and PES. Further studies are needed to demonstrate the long-term safety of different types of DES in patients with diabetes. © 2009 Wiley-Liss, Inc

Long-term clinical outcomes after drug eluting stent implantation in women with de novo coronary lesions: Results from the REAL (REgistro Regionale AngiopLastiche Emilia-Romagna) multicenter registry

Background: The long-term effectiveness of drug eluting stents (DESs) in a real-world setting of female patients is currently unclear. Methods and results: We analyzed long-term follow-up (up to 3 years) data from all female patients with de novo lesions enrolled in a prospective web-based multicenter registry (REAL Registry; study period, July 2002-June 2006) including all 15 hospitals performing PCI in the Emilia-Romagna region of Italy. Among the 3549 women without ST elevation myocardial infarction, 2434 were treated with BMSs alone and 1115 with DESs alone. At 3 years, use of DESs was associated with a lower propensity score adjusted incidence of MACE [cardiac mortality, non-fatal myocardial infarction and target vessel revascularization (TVR); 19.5% vs. 24.4%; HR 0.75, p = 0.006)] and TVR (11.6% vs. 15.6%; HR 0.68, p = 0.004) compared with BMSs. No difference was apparent in terms of adjusted 3-year cardiac mortality or myocardial infarction. Nevertheless, after the first 6 months of follow-up, a non significantly increased risk of myocardial infarction and stent thrombosis was found in the DES group. Conclusions: In this real-world female registry, the use of DESs was associated with a 3-year reduction of TVR and MACE in comparison with the use of BMSs. However, the observed (non-significant) increment of late AMI makes performing larger studies to clarify the long-term safety of DESs mandatory. \ua9 2009 Elsevier Ireland Ltd

Vascular complications after balloon aortic valvuloplasty in recent years: Incidence and comparison of two hemostatic devices

To define the incidence of vascular complications (VC) after balloon aortic valvuloplasty (BAV) in recent years, and to compare the performance of two vascular closure devices (VCD)

In- and out-of-hospital mortality for myocardial infarction during the first wave of the COVID-19 pandemic in Emilia-Romagna, Italy: A population-based observational study

none18noBACKGROUND: The COVID-19 pandemic has put several healthcare systems under severe pressure. The present analysis investigates how the first wave of the COVID-19 pandemic affected the myocardial infarction (MI) network of Emilia-Romagna (Italy). METHODS: Based on Emilia-Romagna mortality registry and administrative data from all the hospitals from January 2017 to June 2020, we analysed: i) temporal trend in MI hospital admissions; ii) characteristics, management, and 30-day mortality of MI patients; iii) out-of-hospital mortality for cardiac cause. FINDINGS: Admissions for MI declined on February 22, 2020 (IRR -19.5%, 95%CI from -8.4% to -29.3%, p&nbsp;=&nbsp;0.001), and further on March 5, 2020 (IRR -21.6%, 95%CI from -9.0% to -32.5%, p&nbsp;=&nbsp;0.001). The return to pre-COVID-19 MI-related admission levels was observed from May 13, 2020 (IRR 34.3%, 95%CI 20.0%-50.2%, p&lt;0.001). As compared to those before the pandemic, MI patients admitted during and after the first wave were younger and with fewer risk factors. The 30-day mortality remained in line with that expected based on previous years (ratio observed/expected was 0.96, 95%CI 0.84-1.08). MI patients positive for SARS-CoV-2 were few (1.5%) but showed poor prognosis (around 5-fold increase in 30-day mortality). In 2020, the number of out-of-hospital cardiac deaths was significantly higher (ratio observed/expected 1.17, 95%CI 1.08-1.27). The peak was reached in April. INTERPRETATION: In Emilia-Romagna, MI hospitalizations significantly decreased during the first wave of the COVID-19 pandemic. Management and outcomes of hospitalized MI patients remained unchanged, except for those with SARS-CoV-2 infection. A concomitant increase in the out-of-hospital cardiac mortality was observed. FUNDING: None.openCampo, Gianluca; Fortuna, Daniela; Berti, Elena; De Palma, Rossana; Pasquale, Giuseppe Di; Galvani, Marcello; Navazio, Alessandro; Piovaccari, Giancarlo; Rubboli, Andrea; Guardigli, Gabriele; Galiè, Nazzareno; Boriani, Giuseppe; Tondi, Stefano; Ardissino, Diego; Piepoli, Massimo; Banchelli, Federico; Santarelli, Andrea; Casella, GianniCampo, Gianluca; Fortuna, Daniela; Berti, Elena; De Palma, Rossana; Pasquale, Giuseppe Di; Galvani, Marcello; Navazio, Alessandro; Piovaccari, Giancarlo; Rubboli, Andrea; Guardigli, Gabriele; Galiè, Nazzareno; Boriani, Giuseppe; Tondi, Stefano; Ardissino, Diego; Piepoli, Massimo; Banchelli, Federico; Santarelli, Andrea; Casella, Giann