ß3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial.

AIMS: Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective ß3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). METHODS AND RESULTS: The ß3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] -0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes. CONCLUSIONS: SPHERE-HF is the first clinical trial to assess the potential benefit of ß3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.

Long-Term Vascular Function in CTO Recanalization: A Randomized Clinical Trial of Ticagrelor vs. Clopidogrel.

BACKGROUND: Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel. It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT). METHODS: The TIGER is a prospective, open-label, two parallel-group controlled clinical trial, which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. RESULTS: Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively) and Doppler data was available in 35 (70%). A high CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p = 0.027), was maintained at follow-up (AUC 34815.22 ± 24,206.06 vs. AUC 22712.47 ± 13,768.95; p = 0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p = 0.933), clopidogrel loading dose-related CBF increased at follow-up (p = 0.039). CONCLUSION: The TIGER trial showed that DAPT with ticagrelor maintained a non-significantly higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with a significant increase at follow-up. The clinical value of such sustained high coronary flow should be evaluated in a larger group of patients. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02211066 (ClinicalTrials.gov number NCT02211066).

Durable polymer everolimus-eluting stents: history, current status and future prospects.

INTRODUCTION: Coronary percutaneous interventions have evolved from plain old balloon angioplasty (POBA) to stent implantation, which itself evolved from bare-metal stents (BMS) to the new biodegradable stents which try to restore endothelial function. Currently, the most commonly used stent is the everolimus-eluting stent. AREAS COVERED: This review will cover the current status of durable polymer everolimus-eluting stent, its history, and future perspectives. Nowadays, the everolimus-eluting stent is the most used device in the acute and chronic settings due to its safety and efficacy. EXPERT OPINION: Durable polymer everolimus-eluting stent, supported by much evidence, has demonstrated its efficacy and safety, not only in de novo artery lesions, but in multiples scenarios, such as the acute setting and diabetic population, becoming one of the most polyvalent stents available. Nowadays, research is focused on the reduction of antiplatelet treatment duration. Similar rates of stent thrombosis with short dual antiplatelet treatment regimens of 1 to 3 months compared to pronged treatment have been observed. However, specific studies should be performed to evaluate this possibility.

Comparison of clinical outcomes in STEMI patients treated with primary PCI according to day-time of medical attention and its relationship with circadian pattern.

OBJECTIVE: Relationship between STEMI time of presentation, its circadian pattern and cardiovascular outcomes is unclear. Our objective is to analyze clinical outcomes of STEMI according to time of presentation and circadian pattern. METHODS: We analyzed data from patients treated within the regional STEMI Network from January 2010 to December 2015. On-hour group included patients treated between 8:00 h and 19:59 h on weekdays, the rest were catalogued as off-hour group. The primary endpoint was 1-year all-cause mortality. Secondary endpoints were 30-day all-cause mortality and in-hospital complications. RESULTS: A total of 8608 patients were included, 44.1% in the on-hour group and 55.9% in the off-hour group. We observed a shorter patient delay and longer system delay in the off-hour group compared to on-hour group with no difference in total ischemic time. At 30-day and 1-year follow-up there were no differences in adjusted all-cause mortality between groups [OR 0.91 (CI95%: 0.73-1.12; p = 0.35) and OR 0.99 (CI95%: 0.83-1.17; p = 0.87), respectively]. A circadian pattern was observed between 9:00 am and 12:30 pm, with no differences in 30-day and 1-year mortality between patients included in this time interval [OR 1.02 (IC95%: 0.81-1.30; p = 0.85) and OR 1.12 (IC95%: 0.92-1.36; p = 0.25) respectively]. CONCLUSIONS: Off-hour STEMI presentation was associated with a shorter patient delay and longer system delay without an increase in total ischemic time. The off-hour presentation was not related to an increase in 1-year all-cause mortality when compared to on-hour. A circadian pattern was found, without differences in 30-day and 1-year mortality.