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Medical treatment and revascularisation
options in patients with type 2 diabetes
and coronary disease
Comment by
Benjamin Scirica,
MD
In this pooled analysis from three landmark trials in coronary artery disease, the investigators
of the COURAGE, BARI 2D, and FREEDOM trials evaluate the long-term benefit of early revas-
cularisation with CABG or PCI when added to optimal medical therapy (OMT) in stable patients
with diabetes. While conceptually similar, these trials had subtle, yet important differences
in randomisation strategies and inclusion criteria with varying extent of coronary disease.
F
or example, COURAGE,
which compared OMT vs PCI
+ OMT excluded patients
who required CABG and therefore
focused on less complex coronary
disease, whereas BARI 2D and
FREEDOM specifically included
patients with multivessel disease. In
contrast to FREEDOM, which ran-
domised patients to PCI vs CABG,
BARI 2D randomised patients to
OMT vs OMT + revascularisation;
the decision for PCI vs CABG was
made prior to randomisation and
used as a stratification variable.
Thus, this is not a straightfor-
ward patient-level analysis from
similarly designed trials. However,
these pooled findings reinforce the
primary messages from each indi-
vidual trial and together provide an
important summary for this common
clinical scenario.
1. CABG + OMT is the best revascu-
larisation strategy in patients with
diabetes and coronary disease, even
single-vessel disease of the LAD.
CABG reduced MI by almost 50%
compared with OMT or PCI, and
compared with PCI, reduced mor-
tality by just over 20%.
2. In patients with less complex dis-
ease who would not be considered
for CABG, PCI, when compared
with OMT alone, does not provide
any benefit in terms of death or
MI. PCI tends to improve anginal
symptoms earlier than OMT, but
it does not improve any “hard”
clinical events.
3. Patients who undergo CABG suf-
fer numerically more strokes, but
that difference is minimal over the
nearly 5-year follow-up.
Importantly, optimal medical
therapy is the cornerstone of sec-
ondary prevention. This includes
antiplatelet therapy, aggressive lipid
control with high-intensity statins,
ezetimibe, and even PCSK9 in-
hibitors, blood pressure control,
and diet and lifestyle modifications.
The choice of anti-hyperglycaemic
strategies should consider agents
with proven cardiovascular benefits.
As recommended by current
practice guidelines, all patients, and
in particular those with diabetes
and symptomatic coronary disease,
should be evaluated by a “heart team”
that includes surgeons and cardiolo-
gists. As these data suggest, in most
stable patients with diabetes with
coronary artery disease, CABG +
OMT is likely to provide the longest
life and fewest number of infarcts.
Dr Scirica is Attending Cardiologist
and Director,
Quality Initiatives,
Cardiovascular
Division, Brigham
and Women’s
Hospital; Associate
Professor of
Medicine, Harvard Medical School;
Senior Investigator, TIMI Study
Group, Boston, Massachusetts.
JOURNAL SCAN
Magnitude of weight loss
and changes in physical
fitness linked with long-
term cardiovascular disease
outcomes in overweight
diabetics
The Lancet Diabetes & Endocrinology
Take-home message
•
In this secondary analysis of the Look AHEAD
trial, investigators found that greater weight
loss and greater change in fitness level was as-
sociated with reduced cardiovascular disease.
This was in contrast to the primary intention-
to-treat analysis, in which the investigators did
not find a reduction in cardiovascular disease
with intensive lifestyle modification.
•
There may be an association between greater
quantity of weight lost and reduced risk of
subsequent cardiovascular disease in over-
weight people with type 2 diabetes.
Abstract
BACKGROUND
Findings from the Look AHEAD trial
showed no significant reductions in the primary
outcome of cardiovascular disease incidence in
adults with type 2 diabetes randomly assigned to
an intensive lifestyle intervention for weight loss
compared with those randomly assigned to diabe-
tes support and education (control). We examined
whether the incidence of cardiovascular disease in
Look AHEAD varied by changes in weight or fitness.
METHODS
Look AHEAD was a randomised clinical
trial done at 16 clinical sites in the USA, recruiting
patients from Aug 22, 2001, to April 30, 2004. In
the trial, 5145 overweight or obese adults aged
45–76 years with type 2 diabetes were assigned
(1:1) to an intensive lifestyle intervention or diabe-
tes support and education. In this observational,
post-hoc analysis, we examined the association
of magnitude of weight loss and fitness change
over the first year with incidence of cardiovascular
disease. The primary outcome of the trial and of
this analysis was a composite of death from car-
diovascular causes, non-fatal acute myocardial
infarction, non-fatal stroke, or admission to hospital
for angina. The secondary outcome included the
same indices plus coronary artery bypass grafting,
carotid endartectomy, percutaneous coronary inter-
vention, hospitalisation for congestive heart failure,
peripheral vascular disease, or total mortality. We
adjusted analyses for baseline differences in weight
or fitness, demographic characteristics, and risk
factors for cardiovascular disease.
FINDINGS
For the analyses related to weight change,
we excluded 311 ineligible participants, leaving a
population of 4834; for the analyses related to fit-
ness change, we excluded 739 participants, leaving
a population of 4406. In analyses of the full cohort
(ie, combining both study groups), over a median
10.2 years of follow-up (IQR 9.5–10.7), individuals
who lost at least 10% of their bodyweight in the
first year of the study had a 21% lower risk of the
primary outcome (adjusted hazard ratio [HR] 0.79,
95% CI 0.64–0.98; p=0.034) and a 24% reduced risk
of the secondary outcome (adjusted HR 0.76, 95%
CI 0.63–0.91; p=0.003) compared with individuals
with stable weight or weight gain. Achieving an in-
crease of at least 2 metabolic equivalents in fitness
change was associated with a significant reduction
in the secondary outcome (adjusted HR 0.77, 95%
CI 0.61–0.96; p=0.023) but not the primary outcome
(adjusted HR 0.78, 0.60–1.03; p=0.079). In analyses
treating the control group as the reference group,
participants in the intensive lifestyle intervention
group who lost at least 10% of their bodyweight had
a 20% lower risk of the primary outcome (adjusted
HR 0.80, 95% CI 0.65–0.99; p=0.039), and a 21%
lower risk of the secondary outcome (adjusted HR
0.79, 95% CI 0.66–0.95; p=0.011); however, change
in fitness was not significantly associated with a
change in the primary outcome.
INTERPRETATION
The results of this post-hoc analysis
of Look AHEAD suggest an association between
the magnitude of weight loss and incidence of car-
diovascular disease in people with type 2 diabetes.
These findings suggest a need to continue to refine
approaches to identify individuals who are most
likely to benefit from lifestyle interventions and to
develop strategies to improve the magnitude of
sustained weight loss with lifestyle interventions.
Association of the magnitude of weight loss
and changes in physical fitness with long-term
cardiovascular disease outcomes in overweight
or obese people with type 2 diabetes: a post-
hoc analysis of the Look AHEAD randomised
clinical trial.
Lancet Diabetes Endocrinol
2016
Aug 30;[Epub ahead of print], The Look AHEAD
Research Group.
Medical treatment and revascularization options in patients with
type 2 diabetes and coronary disease
Journal of American College of Cardiology
Take-home message
•
This study (N = 5034) investigated the effect of optimal medical therapy (OMT) on long-term outcomes
in patients with type 2 diabetes and coronary artery disease. After a median 4.5-year follow-up,
improved results were noted in patients who received coronary artery bypass grafting (CABG) plus
OMT compared with percutaneous coronary intervention (PCI) plus OMT for the primary endpoint (HR,
0.71), death (HR, 0.75), and MI (HR, 0.50), but not stroke (HR, 1.54). There were no marked differences
observed for OMT versus PCI plus OMT.
•
For patients with type 2 diabetes and stable coronary artery disease, CABG plus OMT is the preferred
approach to management, supported by the reduction of the primary endpoint during long-term
follow-up.
Abstract
BACKGROUND
There are scant outcomes data in pa-
tients with type 2 diabetes and stable coronary artery
disease (CAD) stratified by detailed angiographic bur-
den of CAD or left ventricular ejection fraction (LVEF).
OBJECTIVES
This study determined the effect of optimal
medical therapy (OMT), with or without percutaneous
coronary intervention (PCI) or coronary artery bypass
grafting (CABG), on long-term outcomes with respect
to LVEF and number of diseased vessels, including
proximal left anterior descending artery involvement.
METHODS
A patient-level pooled analysis was un-
dertaken in 3 federally-funded trials. The primary
endpoint was the composite of death, myocardial
infarction (MI), or stroke, adjusted for trial and rand-
omization strategy.
RESULTS
Among 5,034 subjects, 15% had LVEF <50%,
77%hadmultivessel CAD, and 28%had proximal left an-
terior descending artery involvement. During a median
4.5-year follow-up, CABG + OMT was superior to PCI +
OMT for the primary endpoint (hazard ratio [HR]: 0.71;
95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002),
death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and
MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not
stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG
+ OMT was also superior to OMT alone for prevention
of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97;
p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p =
0.0001), and was superior to PCI + OMT for the primary
endpoint in patientswith 3-vessel CAD (HR: 0.72; 95%CI:
0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95%
CI: 0.58 to 0.87; p = 0.0012). There were no significant
differences in OMT versus PCI + OMT.
CONCLUSIONS
CABG + OMT reduced the primary
endpoint during long-term follow-up in patients with
type 2 diabetes and stable CAD, supporting this as
the preferred management strategy.
J Am Coll Cardiol
2016 Sep 06;68:985-995,
Mancini GB, Farkouh ME, Brooks MM et al.
As recommended by current practice guidelines, all patients,
and in particular those with diabetes and symptomatic coronary
disease, should be evaluated by a “heart team” that includes
surgeons and cardiologists.
DIABETES
PRACTICEUPDATE ENDOCRINOLOGY
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