This thread is making my head spin.

Everyone in BETonMACE received top standard of care, including statin therapy. Not all patients were on the exact same combination of standard of care (SoC) drugs, since not all patients had the exact same risk factor symptoms. You can look at the BETonMACE ClinicalTrials.gov listing and the AHA and post-AHA slides for info on inclusion criteria, exclusion criteria and the percent of patients on each of the major types of SoC. The point of BETonMACE was to make the one single major difference between the two groups the presence or absence of apabetalone (RVX-208). So patients in the placebo group took their SoC mix (including a statin) plus a placebo pill; patients in the apabetalone group took their SoC mix (including a statin) plus an apabetalone pill. This is standard practice in cardiovascular outcomes trials (CVOTs). The goal in CVOTs is to reduce the residual cardiovascular risk that exists despite patients being on the current top standard of care. As others pointed out, it is unethical to withhold top standard of care in CVOTs. The test drug in question (i.e. apabetalone), is being tested to show superiority (benefit) above the current SoC. 

Every trial has its inclusion and exclusion criteria. For example, in Resverlogix's Phase 2 trials ASSERT, SUSTAIN and ASSURE all had limitations on use of fibrate drugs and niocin/nicotinic acid dose higher than 250 mg. These agents are known to affect HDL levels, and therefore were excluded from use to avoid confounding the observations of apabetalone's effect on HDL and apo-AI. This isn't really withholding SoC though, since HDL isn't really an established risk factor. However, these agents are commonly prescribed for low-HDL folks. If a drug wasn't disallowed on the inclusion/exclusion criteria, then these drugs were not prohibited in the respective trial. 

All other trials besides BETonMACE, ASSERT, ASSURE and SUSTAIN have been 5 weeks long or less and have not really been outcomes studies. These other trials have been in a small number of patients, and have been more like safety and pharmacokinetic studies. Since these other trials are not large outcomes studies in high-risk patients, there isn't really any SoC to worry about including or excluding, other than for certain issues detailed in the respective trials inclusion and exclusion criteria. BETonMACE is the only major outcomes study to be done in high risk patients on much needed SoC. 

The pre-diabetes trial was the closest to an outcomes study. This trial required patients to have "No current use or need for prescription or over-the-counter medication within four days of Visit 1" and did not require patients to be on statins. It wanted to cleanly test if apabetalone had an effect on any aspect of glucose-insulin homeostasis without the confounding issue of patients being on other drugs, especially drugs known to affect glucose control. It was a short trial (less than five weeks on drug) and a small trial (20 patients) and apabetalone did not significantly increase HDL-C or apo-AI. However, apabetalone elicited significant increases in concentration of medium-sized HDL particles, significant decreases in small-sized HDL particles, and significant changes in the lipid composition of the HDL particles. Additionally, there were interesting effects on glucose metabolism.

BDAZ