CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 7, August 2013
290
AFRICA
Drug Trends in Cardiology
Saxagliptin demonstrates no increased risk for cardiovascular
death, heart attack or stroke in the SAVOR cardiovascular
outcomes trial
Results presented at the recent 2013
European Society of Cardiology congress
in Amsterdam, The Netherlands, and
published in the
New England Journal
of Medicine
contribute to on-going
questions concerning the safety of
many diabetes treatments, particularly
regarding the impact of their use on risk
of cardiovascular death, heart attack or
stroke. SAVOR (Saxagliptin Assessment
of Vascular Outcomes Recorded in
patients with diabetes mellitus) is the
largest cardiovascular outcomes trial to
study a diverse population of type 2
diabetes mellitus (T2DM) patients at high
risk for cardiovascular events.
SAVOR was a randomised, double-
blind, placebo-controlled trial of 16 492
patients in more than 700 sites worldwide,
designed to evaluate the cardiovascular
safety and efficacy of saxagliptin in adults
with T2DM at risk for cardiovascular
death, heart attack and stroke, compared
to placebo. The median follow up was
2.1 years and maximum follow up was
2.9 years. Saxagliptin demonstrated no
increased risk for the primary composite
endpoint of cardiovascular death, non-fatal
myocardial infarction (MI) or non-fatal
ischaemic stroke when added to a patient’s
current standard of care (with or without
other anti-diabetic therapies), compared
to placebo.
Recruitment included patients with
T2DM and baseline HbA
1c
levels of 6.5
to 12.0%, on any diabetes treatment
including diet, insulin and/or oral therapy
(excluding GLP-1 agonists and DPP-4
inhibitors) who were at elevated risk for
cardiovascular events according to two
categories:
•
patients
≥
40 years of age with estab-
lished cardiovascular disease, defined
as ischaemic heart disease, peripheral
vascular disease or ischaemic stroke
•
males
≥
55 years of age and females
≥
60 years with at least one of the follow-
ing risk factors: dyslipidaemia, hyper-
tension or current smoking, but with-
out established cardiovascular disease.
Further grouping was based on renal
function, including patients with normal/
mild (eGFR
>
50 ml/min), moderate
(eGFR 30–50 ml/min) or severe (eGFR
<
30 ml/min) renal impairment.
The primary efficacy objective was to
determine, as a superiority assessment,
whether treatment with saxagliptin
compared to placebo (when added to
current background therapy) would result
in a reduction in the composite endpoint
of cardiovascular death, non-fatal MI or
non-fatal ischaemic stroke in patients
with T2DM. Saxagliptin demonstrated no
increased risk in the primary composite
endpoint: 7.3% in the saxagliptin group
versus 7.2% in the placebo group [hazard
ratio (HR): 1.00; 95% confidence interval
(CI): 0.89–1.12; non-inferiority
p
<
0.001;
superiority
p
=
0.99). Saxagliptin did not
meet the primary efficacy endpoint of
superiority to placebo.
Secondary efficacy objectives included
a reduction in the primary composite
endpoint together with hospitalisation for
heart failure, coronary revascularisation
or unstable angina pectoris, and reduction
in all-cause mortality. Hospitalisation for
heart failure, unstable angina or coronary
revascularisation occurred in 12.8% of
the saxagliptin group versus 12.4% in
the placebo group (HR: 1.02; 95% CI:
0.94–1.11;
p
=
0.66). Hospitalisation for
heart failure occurred at a greater rate in
the saxagliptin group (3.5%) than in the
placebo group (2.8%) (HR: 1.27; 95% CI:
1.07–1.51;
p
=
0.007). The pre-specified
secondary endpoint of all-cause mortality
occurred at 4.9% in the saxagliptin group
versus 4.2% in the placebo group (HR:
1.11; 95% CI: 0.96–1.27;
p
=
0.15).
G Hardy
