Insight on New
Several Late-Breaking Clinical Trials
presented at AHA 2016 provide new
insights on lipid therapies.
In the AEGIS-I Trial, C. Michael
Gibson, MS, MD, et al., evaluated the
safety profile of CSL112, an infusible
formulation of human apolipoprotein
A-I (apoA-I), and characterized its
properties among patients with
recent acute myocardial infarction.
1,258 patients were randomized to
either 2 grams of CSL112, 6 grams
of CSL112 or placebo via weekly
infusion for four consecutive doses.
The results of the study, simultaneously published in Circulation, show
that the four weekly infusions of
CSL112 are feasible, well-tolerated
and not associated with any significant changes in liver or kidney
Meanwhile, the MILANO-PILOT
Trial, led by Stephen Nicholls, MD,
et al., examined the effect of five 20
mg/kg weekly infusions of MDCO216 (apoA-I Milano) or placebo on
patients with recent acute coronary
syndrome. The results of the study
show that the infusions of apoA-I Milano were well-tolerated and reduced
HDL-C levels in patients receiving the
treatment. However, the authors note
that “MDCO-216 did not produce a
significant effect on coronary disease
progression, [and] … the findings
from this pilot study do not provide
the evidence required to proceed with
In a third trial evaluating the
effectiveness of a unique drug in
reducing atherogenic lipoproteins,
Sotirios Tsimikas, MD, et al., found
that ionis-angptl3-lRx may show
promise for treating elevated triglycerides and LDL-C in patients with
elevated cholesterol. In this phase
1/2a study, researchers examined
the effects of suppressing ANGPTL3
in 44 healthy volunteers with elevated triglycerides. Results showed
that IONIS-ANGPLT3-LRx reduced
plasma levels of ANGPTL3 levels up
to mean 85%.
Gibson CM, Korjian S, Tricoci P, et al.
the Progression of
The addition of PCSK9 inhibitors
in the treatment of coronary heart
disease (CHD) patients already taking
statins showed incremental benefits
on the progression of coronary atherosclerosis, according to the results
of the GLAGOV Trial presented
during AHA 2016 and simultaneously published in the Journal of the
American Medical Association.
Steven E. Nissen, MD, et al., led
the first intravascular outcome trial
testing the effects of a PCSK9 inhibitor on the regression or progression of
coronary atherosclerosis as measured
The addition of
in the treatment
of coronary heart
health benefits on
by intravascular ultrasound. The study
was a double-blind, placebo-controlled
trial of 968 statin-treated patients
with established CHD at 226 sites in
32 countries. The patients’ average age
was 60, 72% were male, 24% were
smokers and 21% were diabetic.
Statin-treated patients were
randomly assigned to take either the
PCSK9 inhibitor, evolocumab, (420
mg) monthly or placebo for 78 weeks.
Patients underwent an intravascular
ultrasound examination of a single
coronary artery during a clinicallyindicated angiogram at baseline and
then repeated at end of the study.
The results of the study show that
the % atheroma volume decreased in
patients treated with evolocu mab compared to those treated with the placebo
after 76 weeks of treatment. Further,
the patients treated with evolocumab
achieved lower mean, time-weighted
LDL-C levels, and evolocumab induced
plaque regression in a greater percentage of patients than the placebo.
Nicholls SJ, Puri R, Anderson T, et al. JAMA.
HeartMate 3 vs.
HeartMate II in
The HeartMate 3 left ventricular assist
system may be safe and effective, according to the results of the MOMENTUM 3 Trial presented during AHA
2016 and simultaneously published in
the New England Journal of Medicine.
Mandeep R. Mehra, MD, et al.,
evaluated the safety and comparative
effectiveness of the HeartMate 3 left
ventricular assist system to the HeartMate II system in a prospective randomized, controlled trial of advanced
heart failure (HF) patients. Patients
were randomized to receive HeartMate
3 or the HeartMate II irrespective of
the intended use as either bridge to
transplantation or destination therapy
for those ineligible for a transplant.
The primary endpoint of the analysis
evaluated if HeartMate 3 worked as
well as or better than (non-inferior)
HeartMate II in terms of survival free
of debilitating stroke or reoperation to
to the reduction
in the rate of
difference in other
replace or remove the pump.
According to the results, HeartMate
3 provided incremental improvement
in clinical outcomes due to reduction
in the rate of reoperation for pump
malfunction without an apparent difference in other adverse events.
The researchers also found no significant between-group differences in
the rates of death or disabling stroke
but reoperation for pump malfunction
was less frequent in the Heartmate 3
group than the HeartMate II group. ■
Mehra MR, Naka Y, Uriel N, et al. N Engl
J Med. 2016;doi:10.1056/NEJMoa1610426