Efficacy and safety of the endothelin-1 receptor antagonist macitentan in epicardial and microvascular vasospasm; a proof-of-concept study.

Background: Treatment of patients diagnosed with angina due to epicardial or microvascular coronary artery spasm (CAS) is challenging because patients often remain symptomatic despite conventional pharmacological therapy. In this prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept study, we compared the efficacy and safety of macitentan, a potent inhibitor of the endothelin-1 receptor, to placebo in symptomatic patients with CAS despite background pharmacological treatment. Methods: Patients with CAS diagnosed by invasive spasm provocation testing with >3 anginal attacks per week despite pharmacological treatment were considered for participation. Participants received either 10 mg of macitentan or placebo daily for 28 days as add-on treatment. After a wash-out period patients were crossed over to the alternate treatment arm. The primary endpoint was the difference in anginal burden calculated as [1] the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10); and [2] the frequency of angina attacks * severity during medication use compared to the run-in phase. Results: 28 patients of whom 22 females (79%) and a mean age of 55.3 ± 7.6 completed the entire study protocol (epicardial CAS n = 19 (68), microvascular CAS n = 9 (32)). Change in both indices of anginal burden were not different during treatment with add-on macitentan as compared to add-on placebo (duration*severity: -9 [-134 78] vs -45 [-353 11], p = 0.136 and frequency*severity: -1.7 [-5.8 1.2] vs -1.8 [-6.2 0.3], p = 0.767). The occurrence and nature of self-reported adverse events were closely similar between the treatment phase with macitentan and placebo. Conclusion: In patients with angina due to epicardial or microvascular CAS despite background pharmacological treatment, 28 days of add-on treatment with the ET-1 receptor antagonist, macitentan 10 mg daily, did not reduce anginal burden compared to add-on treatment with placebo.Trial Registrationhttps://trialsearch.who.int/, Identifier: EUCTR2018-002623-42-NL. Registration date: 20 February 2019.

The relationship between the number of preprocedural circulating endothelial progenitor cells and angiographic restenosis following coronary artery stent placement.

OBJECTIVE: In animals, endothelial progenitor cells (EPCs) beneficially influence the repair of the coronary vessel wall after damage by stent placement. However, their role in humans is less well understood. In the present study, the authors aimed to evaluate the relationship between the number of preprocedural EPCs defined as CD34+/KDR+/CD133+ cells and angiographic late loss as a measure of the growth of in-stent intimal hyperplasia. DESIGN SETTING PATIENTS AND INTERVENTIONS: The 59 study patients were treated in the authors' clinic with a Genous EPC capturing stent, a bare metal stent (BMS) or a drug-eluting stent, and angiographic follow-up occurred between 6 and 13 months. RESULTS: The authors found no relationship between preprocedural EPCs and angiographic late loss, irrespective of stent type. Though statistically not significant, patients with a high number of preprocedural CD34 cells and treated with a Genous stent or BMS showed a numerically higher late loss (in Genous patients: 1.03±0.76 mm vs 0.71±0.50 mm, p=0.15; in BMS patients: 1.06±0.73 mm vs 0.35±0.62 mm, p=0.08). CONCLUSIONS: Considering these and other varied observations, further studies aimed at identifying the biological mechanism and the individual roles of EPCs and/or CD34 cells in endothelial repair after coronary vessel stenting are needed.

ST-segment deviation on the admission electrocardiogram, treatment strategy, and outcome in non-ST-elevation acute coronary syndromes A substudy of the Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) Trial.

BACKGROUND: We assessed the prognostic significance of the presence of cumulative (Sigma) ST-segment deviation on the admission electrocardiogram (ECG) in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T randomized to a selective invasive (SI) or an early invasive treatment strategy. METHODS: A 12-lead ECG obtained at admission was available for analysis from 1163 patients. The presence and magnitude of ST-segment deviation was measured in each lead, and absolute ST-segment deviation was summed. The effect of treatment strategy was assessed for patients with or without SigmaST-segment deviation of at least 1 mm. RESULTS: The incidence of death or myocardial infarction (MI) by 1 year in patients with SigmaST-segment deviation of at least 1 mm was 18.0% compared with 11.1% in patients with SigmaST-segment deviation of less than 1 mm (P = .001). Among patients with SigmaST-segment deviation of at least 1 mm, the incidence of death or MI was 21.9% in the early invasive group compared with 14.2% in SI group (P < .01). However, we observed a significantly higher rate of MI after hospital discharge among patients with SigmaST-segment deviation of at least 1 mm randomized to SI who did not undergo angiography compared with patients who underwent angiography before discharge (10.9% vs 2.4%, P = .003). In a forward logistic regression analysis, the presence of ST-segment deviation was an independent predictor for failure of medical therapy (coronary angiography within 30 days after randomization in the SI group) (odds ratio, 1.56; 95% confidence interval, 1.12-2.18; P = .009). CONCLUSION: Patients with non-ST-elevation acute coronary syndrome and an elevated troponin T and SigmaST-segment deviation of at least 1 mm are at increased risk of death or MI, more often fail on medical therapy, and more often experience a spontaneous MI after discharge when angiography was not performed during initial hospitalization.

Randomized trial comparing same-day discharge with overnight hospital stay after percutaneous coronary intervention: results of the Elective PCI in Outpatient Study (EPOS).

BACKGROUND: Percutaneous coronary intervention (PCI) in a day-case setting might reduce logistic constraints on hospital resources, but data on safety are limited. We evaluated the safety and feasibility of same-day discharge after PCI. METHODS AND RESULTS: Eight hundred consecutive patients scheduled for elective PCI by femoral approach were randomized to same-day discharge or overnight hospital stay. Four hours after PCI, patients were triaged as suitable for early discharge or not. Suitable patients were discharged immediately or kept overnight, according to randomization. Patients with an indication for extended hospital stay were not discharged regardless of randomization. Primary end points were death, myocardial infarction, coronary artery bypass graft surgery, repeat PCI, or puncture-related complications occurring within 24 hours after PCI. A total of 403 patients were assigned to same-day discharge, of whom 77 (19%) were identified for extended observation; 397 patients were assigned to overnight stay, of whom 85 (21%) were identified for extended observation. Among all patients, the composite primary end point occurred in 9 (2.2%) same-day discharge patients and in 17 (4.2%) overnight stay patients (risk difference, -0.020; 95% CI, -0.045 to -0.004; P for noninferiority <0.0001). Among patients deemed suitable for early discharge, the composite end point occurred in 1 of 326 (0.3%) same-day discharge patients and 2 of 312 (0.6%) overnight-stay patients (risk difference, -0.003; 95% CI, -0.014 to 0.007; P for noninferiority <0.0001). The last 3 events were related to puncture site. CONCLUSIONS: Same-day discharge after elective PCI is feasible and safe in the majority (80%) of patients selected for day-case PCI. Same-day discharge does not lead to additional complications compared with overnight stay.