ESC Congress 2017 In Review -- Main Edition - 18

Late-Breaking Clinical Trials

apixaban (n = 753) or parenteral heparin and transition
to warfarin (n = 747). Dr Ezekowitz noted that, prior to
randomisation, 61% of the patients had not received
any anticoagulation therapy.
Patients in the apixaban group could be treated
with a loading dose of 10 mg unless they were aged
≥80 years, weighed ≤ 60 kg, or had a serum creatinine
level ≥ 1.5 mg/dL. Patients who met 2 of these criteria
received a loading dose of 5 mg.
In the ITT population, apixaban treatment significantly reduced the rate of strokes compared with usual
care (0 vs 6; P = .0164). SE events did not occur in either
group (Figure 1). However, the trial was not powered to
show differences in efficacy results.

Proportion of Patients
with Stroke/SE

Figure 1. Stroke and Systemic Embolism Outcomes in EMANATE
Apixaban (events: 0/753)
Heparin/VKA (events: 6/747

.020

5 ischaemic, 1 haemorrhagic stroke with 0 SE events

.015
.010
.005

P = .0164

.000

Number at risk
Apixaban
Heparin/VKA

130

Time to Stroke/SE (days)
752
747

6145
65

199
231

55
88

One patient's adjudicated stroke date was one day prior to randomisation;
thus at day 0, only 1499 were at risk for stroke. No patients had SE. ITT population.

ITT, intention-to-treat; SE, systemic embolism; VKA, vitamin K antagonist.
Reproduced with permission from MD Ezekowitz, MBChB, DPhil.

The investigators assessed safety outcomes in a safety
population (n = 1,456) who were randomised and received
one or more doses of the study drug. Major bleeding
occurred in 3 patients in the apixaban subgroup and 6 in
the usual care subgroup, while CRNM bleeding occurred
in 11 and 13 patients, respectively, in the 2 subgroups. Two
patients in the apixaban subgroup and 1 patient in the
usual care subgroup died, said Dr Ezekowitz. He noted
that 342 of the 753 patients in the apixaban subgroup
received a loading dose. In this subgroup, there were no
strokes or SE events; however, 1 death, 1 major bleed,
and 4 CRNM bleeds occurred in this subgroup, he added.
To assess the role of image guidance accompanying
cardioversion, the investigators performed imaging in
840 patients prior to cardioversion. Using echocardiography, investigators identified left atrial appendage thrombi
in 61 patients; 30 of these patients were receiving apixaban and 31 were receiving heparin/VKA. Complete followup occurred in these 61 patients, and no outcome events
occurred in either subgroup. The investigators repeated
imaging studies after a mean of 37 days in 23 patients
receiving apixaban and 18 receiving heparin/VKA. They
found that the thrombi had resolved in 12 patients receiv-

October 2017

ing apixaban and in 10 patients receiving heparin/VKA,
and these patients with evidence of thrombus resolution
underwent cardioversion.
The results of this trial support use of apixaban in
patients with AF undergoing cardioversion, concluded
Dr Ezekowitz.

Results of the HPS3/TIMI55REVEAL Trial
Written by Phil Vinall

Anacetrapib is a potent inhibitor of cholesteryl ester
transfer protein (CETP). Trials of other CETP inhibitors
have been stopped early due to unexpected cardiovascular hazards or apparent lack of efficacy. REVEAL trial
[NCT01252953], assessed the efficacy and safety of
adding anacetrapib to effective doses of atorvastatin
among patients with established atherosclerotic vascular disease. The primary results, presented by Martin
J. Landry, MD, University of Oxford, London, United
Kingdom, showed that the addition of anacetrapib
to intensive therapy with atorvastatin reduced major
coronary events [HPS3/TIMI55-REVEAL Collaborative
Group. N Engl J Med. 2017].
REVEAL was a randomised, double-blind, placebocontrolled clinical trial in patients with pre-existing atherosclerotic vascular disease. The primary outcome was
the first major coronary event, defined as the occurrence
of coronary death, myocardial infarction (MI), or coronary revascularisation. Secondary outcomes were major
atherosclerotic events (coronary death, MI or presumed
ischaemic stroke), major vascular events (major coronary
event or presumed ischaemic stroke), and presumed
ischaemic stroke on its own.
The study comprised individuals aged > 50 years
with pre-existing atherosclerotic vascular disease on
a background atorvastatin regimen (20 or 80 mg daily). Patients (mean age 67 years; 84% men) were randomised to anacetrapib 100 mg daily or matching placebo. At the randomisation visit (after at least 8 weeks
on a protocol-defined atorvastatin regimen) 88% of
patients had coronary heart disease, 22% cerebrovascular disease, 8% peripheral arterial disease, and 37%
had diabetes mellitus. Mean plasma LDL-C was 61 mg/dL,
HDL-C was 40 mg/dL, and non-HDL-C was 92 mg/dL.
Follow-up (median duration of 4.1 years) is 99.8%
complete. During the median follow-up of about 4 years,
90% of patients were adherent to the blinded therapy,
and significantly fewer major coronary events had
occurred in patients treated with anacetrapib (rate ratio
[RR], 0.91; 95% CI, 0.85 to 0.97; P = .004) compared
with placebo (Figure 1).

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