Double-blind, placebo-controlled evaluation of biorest liposomal alendronate in diabetic patients undergoing PCI: The BLADE-PCI trial.

BACKGROUND: Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM. METHODS: Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography. RESULTS: From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P = .35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups. CONCLUSIONS: Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

One-year outcomes of supersaturated oxygen therapy in acute anterior myocardial infarction: The IC-HOT study.

BACKGROUND: Supersaturated oxygen (SSO2 ) has recently been approved by the U.S. Food and Drug Administration for administration after primary percutaneous coronary intervention (pPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) based on its demonstration of infarct size reduction in the IC-HOT study. OBJECTIVES: To describe the 1-year clinical outcomes of intracoronary SSO2 treatment after pPCI in patients with anterior STEMI. METHODS: IC-HOT was a prospective, open-label, single-arm study in which 100 patients without cardiogenic shock undergoing successful pPCI of an occluded left anterior descending coronary artery were treated with a 60-min SSO2 infusion. One-year clinical outcomes were compared with a propensity-matched control group of similar patients with anterior STEMI enrolled in the INFUSE-AMI trial. RESULTS: Baseline and postprocedural characteristics were similar in the two groups except for pre-PCI thrombolysis in myocardial infarction 3 flow, which was less prevalent in patients treated with SSO2 (9.6% vs. 22.9%, p = .02). Treatment with SSO2 was associated with a lower 1-year rate of the composite endpoint of all-cause death or new-onset heart failure (HF) or hospitalization for HF (0.0% vs. 12.3%, p = .001). All-cause mortality, driven by cardiovascular mortality, and new-onset HF or HF hospitalization were each individually lower in SSO2 -treated patients. There were no significant differences between groups in the 1-year rates of reinfarction or clinically driven target vessel revascularization. CONCLUSIONS: Infusion of SSO2 following pPCI in patients with anterior STEMI was associated with improved 1-year clinical outcomes including lower rates of death and new-onset HF or HF hospitalizations.

Platelet Reactivity and Clinical Outcomes After Coronary Artery Implantation of Drug-Eluting Stents in Subjects With Peripheral Arterial Disease: Analysis From the ADAPT-DES Study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).

BACKGROUND: Patients with peripheral arterial disease (PAD) have high rates of adverse cardiovascular events after percutaneous coronary intervention and may additionally have heightened platelet reactivity. This study assessed the relationship between platelet reactivity and clinical outcomes after percutaneous coronary interventions among subjects with and without PAD. METHODS AND RESULTS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. Platelet reactivity was assessed by the VerifyNow point-of-care assay; high on-treatment platelet reactivity (HPR) was defined as P2Y12 reaction units >208. A propensity-adjusted multivariable analysis was performed to determine the relationship between PAD, platelet reactivity, and subsequent adverse events (definite or probable stent thrombosis, all-cause mortality, myocardial infarction, and clinically relevant bleeding). Among 8582 patients, 10.2% had a history of PAD. Patients with PAD were older and more likely to have comorbid conditions; however, mean P2Y12 reaction units and HPR were not significantly different between PAD and no PAD groups. Patients with PAD had higher 2-year rates of all-cause mortality, myocardial infarction, stent thrombosis, and clinically relevant bleeding. Associations between HPR and adverse events were similar in PAD and no PAD groups, without evidence of interaction; however, adverse event rates were highest among subjects with both PAD and HPR. In a propensity-adjusted multivariable model, both PAD and HPR were independent predictors of myocardial infarction at 2 years. CONCLUSIONS: A history of PAD was associated with ischemic and bleeding outcomes 2 years after successful coronary drug-eluting stent implantation; however, these associations did not seem to be directly mediated by heightened platelet reactivity. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Assessing the impact of carryover effects on the variances of estimators of treatment differences in crossover designs.

Different models that include carryover effects have been studied in the optimal design literature. It has been suggested that the use of these models results in increased variances of estimated contrasts of the direct treatment effects, leading to inferior estimators in terms of precision. Under a number of models and selected designs, we present variance expressions for the pairwise differences of direct treatment effects and observe that adjusting for carryover effects need not affect the precision of estimators negatively. We investigate the existence of designs that produce estimators with relatively small variances under all models considered. We conclude that even if a model is not correct, it can still be useful in increasing the precision of estimators for treatment contrasts.