The drug works so well, he said, “Based on the
criteria used for renal denervation, we would have
had a total of only 15 patients who would qualify.”
In the live program, “Best of ESC,” Dr. Sharma
noted, “What grabbed me the most is that these
are old drugs changing paradigms with an excellent
outcome. These [drugs] are as cheap as chips; this
is important in the current financial climate. I am
concerned about the impact on ethnicity, because
it is the black population who is more likely to
have resistant hypertension and impaired glucose
tolerance. In Africa and South America where
there are limited resources, these drugs could be
revolutionary.” Added Dr. Fox, “These are generic
therapies that could be added to standard of care
with widespread applicability and that is an important take-home from this Congress.”
Situation Improves for Sitagliptin
It has been the worst of times for a number of
diabetes drugs. Cardiologists found reason for caution after evidence that some new agents to treat
diabetes may be associated with increased CV risk
that could wipe out any gains from better glycemic control. It was at the 2014 ESC meeting, for
example, where Dr. Sharma emphasized that good
“What grabbed me the
most is that these are old
drugs changing paradigms
with an excellent outcome.
These [drugs] are as cheap
as chips; this is important
in the current financial
climate.” — Keith A. A. Fox, MB, ChB
glycemic control benefits microvascular disease
but not macrovascular disease. Consequently, he
said, “We need to ease off on the ‘sweet spot’ for
glycated hemoglobin and focus more on other risk
factors for atherosclerosis because in high-risk
individuals, there is evidence long-acting insulins
have precipitated MI and now the glitazones and
gliptins have been associated with heart failure.”
For example, SAVOR-TIMI 53 (the Saxagliptin
Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) trial was a large international clinical trial that randomized patients to a
selective dipeptidyl peptidase 4 (DPP-4) inhibitor or
placebo. According to John J.V. McMurray, MD, a
professor at the University of Glasgow, “The results
suggested that the drug might increase the risk of
38 CardioSource WorldNews
warning to the label for “the gliptins”—sitagliptin,
heart failure (and) heart failure is the most diabetasaxagliptin, linagliptin, and alogliptin. In a stategenic diseases there is; anywhere between 30% and
ment, the FDA said the medications “may cause
50% of heart failure patients have diagnosed or
joint pain that can be severe and disabling,” and
undiagnosed diabetes.” We need new treatments,
the agency “has added a new Warning and Precaubut those safety concerns were a major stumbling
tion about this risk to the labels of all medicines in
block. However, Dr. McMurray says, with new data,
this drug class.” (The FDA release is here: fda.gov/
things look better now.
Drugs/DrugSafety/ucm459579.htm)
At ESC.15, investigators presented further prespecified analysis of the larger study called TECOS (Trial
Evaluating Cardiovascular
TECOS:
Failure-related
Outcomes
TABLE
3 TECOS:Heart
Heart Failure-related
Outcomes
Outcomes with Sitagliptin).
Sitagliptin
vs.
Placebo
Sitagliptin vs. Placebo
The initial TECOS findings,
Sitagliptin
Control
Hazard Ratio
presented earlier this year
(n=7,332)
(n=7,339)
(95% CI)
p Value
at the American Diabetes
Hospitalization for HF
228 (3.1%)
229 (3.1%)
1.00 (0.84-1.20)
0.95
Association, were adjusted
Adjusted for baseline HF
1.00 (0.83-1.20)
0.98
to control for baseline heart
Multivariable adjusted
1.02 (0.83-1.26)
0.82
failure and the results left
Hospitalization for HF or CV
538 (7.3%)
525 (7.2%)
1.02 (0.90-1.14)
0.81
death
some unanswered questions.
Adjusted for baseline HF
1.02 (0.90-1.15)
0.74
(Such as, so what is the effect
Hospitalization for HF or all685 (9.3%)
682 (9.3%)
1.00 (0.90-1.11)
0.93
of the drug on HF?) Darren
cause death
McGuire, MD, first author of
*CI = confidence intervals; CV = cardiovascular; HF = heart failure; TECOS = Trial
EvaluaIng
Cardiovascular
the study, from the UniverOutcomes
with
SitaglipIn.
sity of Texas Southwestern
Medical Center, Dallas, TX,
told the media, “Now we
present unadjusted analyses [also pre-specified]
OK, let’s end this discussion of diabetes drugs
with identical results, and we complement these
on a high note. As this issue of CSWN was going
with mulitivariable analyses—all yielding the idento press, results were announced for a major trial
tical conclusion: no signal of any sort for heart
evaluating empagliflozin, a selective inhibitor of
failure risk with sitagliptin (TABLE 3). No matter
sodium glucose cotransporter 2 that has been approved for type 2 diabetes. The drug significantly
how we sliced and diced the data, the same result
reduced the risk of the combined endpoint of CV
was observed.”
A second trial presented at ESC also may calm death, non-fatal heart attack, or non-fatal stroke
by 14% when added to standard of care in patients
some frayed nerves in the industry. This study
with type 2 diabetes at high risk of CV events.5
looked at a glucagon-like peptide-1 (GLP-1) for reducing HbA1c in people with type 2 diabetes and
Over a median of 3.1 years, there was a 38% rerecent ACS. Lixisenatide did not increase or deduction in CV death, with no significant difference
crease the rate of CV events compared to placebo,
in the risk of non-fatal MI or non-fatal stroke.
according to the results of ELIXA (Evaluation of
Our former editor-in-chief of CardioSource
Lixisenatide in Acute Coronary Syndrome). LixWorldNews, Christopher P. Cannon, MD, of
isenatide also seemed safe in patients with a hisBrigham and Women’s Hospital, who was not
tory of heart failure, with similar hazard ratios
involved in the study, said, “The EMPA-REG
for active therapy and placebo. However, among
OUTCOME trial results are encouraging for
the patients who were hospitalized for HF during
health care professionals and their patients.
follow-up, the risk of all-cause death was n inePatients in the study were already being treated
fold greater than those who were not hospitalized with medications that have been proven to reduce
for heart failure.
cardiovascular events. The observation that empaAfter the latest data were presented, Dr.
gliflozin provided additional cardiovascular death
Sharma noted that TECOS was a noninferiority
reduction on top of these other medications is a
trial, but he remained optimistic: “We still should
very important finding.”
not be punching our arms in the air over this but
although glycemic control has a modest effect on
Depression: The Strongest Predictor of
the heart, it has a very significant effect on microAngina
vascular effects. And the fact that we now can use
Patients with depression, whether women or men,
another oral hypoglycemic effect to prevent microare three times more likely to experience more
vascular complications—like retinopathy, rememfrequent chest pain than those without depression.
ber blindness due to diabetes is the most common
This was found to be true in patients with and
cause of blindness today—is a very big deal.”
without obstructive coronary artery disease.
One piece of bad news: while many people
The study included 5,825 adults enrolled in
were on their way to the ESC meeting, the U.S.
the Emory Cardiovascular Biobank. Importantly,
Food and Drug Administration (FDA) added a new reducing the severity of depression symptoms
October 2015