New Data Showed ACTOS(R) (pioglitazone HCl) Prevented Progression of Atherosclerotic Plaque Volume in Patients With Type 2 Diabetes
31/03/2008 19:16
PR Newswire
CHICAGO, March 31 /PRNewswire/ --
- Data Expands Body of Evidence in High Risk Population Using IVUS, a
Unique Marker for Coronary Atherosclerosis
New data from a clinical trial using intravascular ultrasound (IVUS)
technology found that in patients living with type 2 diabetes, ACTOS(R)
(pioglitazone HCl) reduced the atherosclerotic burden in the coronary
arteries compared to the sulphonylurea glimepiride, and prevented progression
compared to baseline.
Results from the PERISCOPE (Pioglitazone Effect on Regression of
Intravascular Sonographic Coronary Obstruction Prospective Evaluation) trial
have today been simultaneously presented as a late breaker at the 57th Annual
Scientific Session of the American College of Cardiology and published
on-line by the Journal of the American Medical Association (JAMA).
PERISCOPE is the first clinical trial to examine the effects of an oral
antidiabetic medication on the development of coronary atherosclerosis in
patients with type 2 diabetes using IVUS technology. IVUS measures the volume
of plaque build-up in the coronary arteries, a marker of coronary
atherosclerosis. The 18-month trial, involving 543 patients, was conducted in
97 centres in the USA, Canada and Latin America.
The analysis demonstrated a statistically significant difference in
percent change in coronary artery atheroma volume (PAV) in favour of ACTOS
treatment compared to glimepiride treatment. The data showed that patients
treated with glimepiride exhibited progression of coronary atherosclerosis,
whilst in contrast the ACTOS arm showed no progression of coronary
atherosclerosis over the 18-month period from the initial baseline
measurement.
"The findings of PERISCOPE represent a fundamental observation
demonstrating that pioglitazone, in addition to controlling blood sugar,
favourably influences the development of coronary artery atherosclerosis, the
process that is responsible for the premature death of 80 percent of type 2
diabetic patients," commented Mark Kearney, Professor of Cardiology,
University of Leeds, UK.
"This is further robust evidence that pioglitazone has a beneficial
effect on coronary atherosclerosis in patients with diabetes. Importantly,
this effect is seen on top of good treatment with statins and other
cardiovascular drugs," added Martin Cowie, Professor of Cardiology, National
Heart & Lung Institute, Imperial College London.
Cardiovascular safety data was collected by looking at macrovascular
events and episodes of congestive heart failure (CHF). The number of episodes
of a common cardiovascular endpoint of cardiovascular mortality, non-fatal
MI, or non-fatal stroke was 6 (2.2 percent) in glimepiride patients and 5
(1.9 percent) in ACTOS-treated patients. The number of hospitalisations due
to CHF were equivalent in both arms. In the ACTOS-treated group, eight
patients experienced a bone fracture, none involving the hip or spine.
This trial adds to the body of cardiovascular data for ACTOS. ACTOS
studies, conducted over the past 10 years in more than 16,000 patients,
including short- and long-term trials, as well as prospective and
observational studies, have shown no evidence that ACTOS is associated with
an increased risk of heart attack, stroke, or death.
The data are consistent with the findings of the CHICAGO (Carotid
intima-media tHICkness in Atherosclerosis using pioGlitazOne) trial. Both
PERISCOPE and CHICAGO support the findings of the PROactive (PROspective
PioglitAzone Clinical Trial In MacroVascular Events) trial, which showed that
ACTOS was not associated with an increased risk of heart attack, stroke or
death.
Atherosclerosis is a condition that leads to reduced or blocked blood
flow, and is accelerated in patients with type 2 diabetes.
Atherosclerosis-related cardiovascular disease is the leading cause of death
and disability in people with type 2 diabetes. Published data shows that
slowed progression and reductions in atheroma volume lessens the incidence of
a second heart attack.
Note to Editors
CHICAGO
The CHICAGO (Carotid intima-media tHICkness in Atherosclerosis using
pioGlitazOne) trial, published in JAMA in 20061, demonstrated that ACTOS
significantly slowed progression of carotid intima-media thickness (CIMT) in
patients with type 2 diabetes, compared with the sulphonylurea glimepiride,
over an 18-month period. CIMT is a marker of coronary atheroscelerosis and
independently predicts subsequent cardiovascular events.
PROactive
In PROactive, a cardiovascular outcome study, 5238 patients with type 2
diabetes mellitus and preexisting major macrovascular disease were randomised
to pioglitazone or placebo in addition to existing antidiabetic and
cardiovascular therapy, for up to 3.5 years2. Although the study failed
regarding its primary endpoint, which was a composite of all-cause mortality,
non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg
amputation, coronary revascularisation and leg revascularisation, the results
suggest that there are no long-term cardiovascular concerns regarding use of
pioglitazone. However, the incidences of oedema, weight gain and heart
failure were increased. No increase in mortality from heart failure was
observed.
ACTOS(R) (pioglitazone HCl)
In Europe, pioglitazone is indicated in the treatment of type 2 diabetes
mellitus as: Monotherapy
- in patients (particularly overweight patients) inadequately controlled
by diet and exercise for whom metformin is inappropriate because of
contraindications or intolerance
Dual oral therapy in combination with
- Metformin, in patients (particularly overweight patients) with
insufficient glycaemic control despite maximal tolerated dose of monotherapy
with metformin
- A sulphonylurea, only in patients who show intolerance to metformin or
for whom metformin is contraindicated, with insufficient glycaemic control
despite maximal tolerated dose of monotherapy with a sulphonylurea.
Triple oral therapy in combination with
- metformin and a sulphonylurea, in patients (particularly overweight
patients) with insufficient glycaemic control despite dual oral therapy.
Pioglitazone is also indicated for combination with insulin in type 2
diabetes mellitus patients with insufficient glycaemic control on insulin for
whom metformin is inappropriate because of contraindications or intolerance.
Pioglitazone is contraindicated in patients with:
- Hypersensitivity to the active substance or to any of the excipients
- Cardiac failure or history of cardiac failure (NYHA stages I to IV)
- Hepatic impairment
- Diabetic ketoacidosis.
Some patients with long-standing type 2 diabetes mellitus and heart
disease or previous stroke who were treated with Actos and insulin
experienced the development of heart failure. Patients should consult their
doctor as soon as possible if they experience signs of heart failure such as
unusual shortness of breath or rapid increase in weight or localised swelling
(oedema).
Takeda also manufactures Competact(R), which combines two widely used
diabetes treatments (metformin and pioglitazone) in a convenient single
tablet, to be taken twice daily. COMPETACT(R) was first launched in Europe in
October 2006. Competact(R) 15mg/850mg tablets contain 15mg pioglitazone as
hydrochloride and 850mg of metformin hydrochloride.
Indication: Treatment of type 2 diabetes mellitus patients, particularly
overweight patients, who are unable to achieve sufficient glycaemic control
at their maximally tolerated dose of oral metformin alone.
Takeda Global Research & Development Center
Based in Deerfield, USA, and London, Takeda Global Research & Development
Center, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company
Limited, the largest pharmaceutical company in Japan. Takeda Global Research
& Development was established in 2004 and is responsible for Takeda's
clinical research and development in the U.S. and Europe, supporting clinical
and product development activity for Takeda commercial organizations in the
U.S. - Takeda Pharmaceuticals North America, Inc, and in Europe: six sales
and marketing companies, respectively. With a robust pipeline of compounds in
development for diabetes, cardiovascular disease and other conditions, Takeda
rapidly brings innovative products to market to improve patient health and
enhance the practice of medicine. To learn more about the company, visit
http://www.tgrd.com.
References
1) Mazzone T, Meyer P, Feinstein SB et al. Effect of
Pioglitazone Compared with Glimepiride on Carotid Intima-Media Thickness
in Type 2 Diabetes. JAMA 2006; 296: 2572-2581
2) Dormandy JA, Charbonnel B, Eckland DJA et al. Secondary
Prevention of Macrovascular Events in Patients with Type 2 Diabetes in
the PROactive Study (PROspective pioglitAzone Clinical Trial In
macroVascular Events): A Randomised Controlled Trial. Lancet 2005;
336:1279-89
Contacts: Richard Kenyon Takeda Pharmaceuticals Europe +44-207-632-9351 (E.U. office); Helen Crow Ketchum +44-207-611-3654 helen.crow@ketchum.com