E-BOOKS, PACE LINK, GUIDELINES, STUDIES & TRIALS _____________________________
E-BOOKS AND PACE LINK
1. DAPA-HF SGLT2i treatment effect not dependent on age or health status at baseline. Effect of Treatment According to Age in the Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF). Presented during the AHA Scientific Sessions 2019 by John J V McMurray, (University of Glasgow, Glasgow, United Kingdom).
2. GALILEO Trial. GALILEO trial (Global Study Comparing a rivAroxaban-based Antithrombotic Strategy to an antipLatelet-based Strategy After TAVR) examined whether a rivaroxaban-based strategy was superior to an antiplatelet-based strategy in reducing death and thromboembolic events in patients after successful TAVR without an ongoing indication for oral anticoagulation (such as atrial fibrillation).
In patients undergoing TAVR and without any indication for following oral anticoagulation, a regime of rivaroxaban-based therapy was associated with an increased risk of all-cause death or thromboembolic events and bleeding events when compared to an antiplatelet-based strategy. In contrast, in a substudy with cardiac 4DCT, the proportion of patients with parameters of subclinical leaflet thrombosis were reduced in those treated with rivaroxaban-based strategy compared to an antiplatelet-based regime.
3. EVAPORATE TRIAL. Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides (200-499mg/dl) on Statin Therapy (EVAPORATE Study)
This mechanistic study using CT coronary angiography showed that icosapent ethyl as adjunct to statin yielded significant changes in most plaque markers, indicative of slowing of plaque progression at 9 months. The primary endpoint of low attenuation plaque was not significant at this interim timepoint, but the study will continue to 18 months as planned.
Plaque progression over time can be assessed with multiple CT angiographies, and it has been used to assess the effect of therapies on atherosclerotic plaque progression.
The REDUCE-IT trial showed that treatment with icosapent ethyl reduced the risk of the primary endpoint of CV death, MI, stroke, coronary revascularization and unstable angina by 25%. The current study was a mechanistic study with the aim of obtaining insight into the mechanism through which icosapent ethyl exerts the beneficial effects seen in REDUCE-IT.
4. AROANG STUDY
RNA Interference Targeting Hepatic Angiopoietin-Like Protein 3 Results in Prolonged Reductions in Plasma Triglycerides and LDL-C in Human Subjects (AROANG1001 study)
Presented during the AHA Scientific Sessions 2019 by Gerald F Watts (Univ of Western Australia, Royal Perth Hosp, Perth, Australia).
Introduction and methods
ANGPTL3 is a key regulator of lipid and lipoprotein metabolism with multiple potential nodes of action. Loss-of-function mutations in ANGPTL3 have been found to lead to low LDL-C, VLDL-C, HDL-C and triglycerides (TG), and genome-wide association studies suggested that these mutations are associated with lower risk of CVD. There is no known adverse phenotype associated with a genetic deficiency in ANGPTL3.
ANGPTL3 is primarily synthesized in hepatocytes. ANGPTL3 can be silenced by RNA interference with the specific siRNA ARO-ANG3 (with Arrowhead’s TRiM platform). ARO-ANG3 is administered subcutaneously and is targeted at the liver, where it specifically induces degradation of the ANGPLT3 mRNA. This induces deep and durable silencing of the ANGPTL3, while avoiding off-target effects.
The AROANG1001 study was a phase 1/2a clinical study to test the safety and tolerability of ARO-ANG3 in healthy volunteers. Conclusion
This single ascending dose study of ARO-ANG3, an RNAi therapeutic that specifically silences ANGPTL3 mRNA in the liver, showed dose-dependent reductions in fasting serum ANGPTL3. Moreover, reductions in fasting TG, VLDL-c, LDL-c and HDL-c were seen, similar to those reported in ANGPTL3 loss-of-function carriers. ARO-ANG3 had a favourable safety and tolerability profile. Multi-dose studies in patients with NAFLD, hyperlipidemia on statins , familial hypercholesterolemia, and severe hypertriglyceridemia are underway.