http://www.theheart.org/article/1438055.do?utm_medium=email&utm_source=20120826_ESC2012_world_2&utm_campaign=newsletter
It's time to shift some of the attention paid to lipid-lowering drugs onto therapies that fight vascular inflammation, according to a number of experts speaking on the opening day of the European Society of Cardiology (ESC) 2012 Congress.
Statin and aspirin studies tracking markers of inflammation
show that "the magnitude of this disease associated with inflammation
is at least as large as that of lipids or blood pressure," Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA) told heartwire here.
Ridker points out that the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)—for which he was primary investigator—showed that rosuvastatin
(Crestor, AstraZeneca) reduced major adverse events 44% compared with
placebo in patients with low LDL cholesterol but a high level of
C-reactive-protein (CRP), a common marker of systematic inflammation.
JUPITER showed a 50% decrease in LDL and a 37% decrease in CRP at 12
months, and the risk reduction was greater in patients with greater CRP
reduction.
In his ESC talk, Ridker described two new studies getting under way looking at anti-inflammatory agents for reducing CV risk.
"Statins are weak anti-inflammatory drugs, but
we've shown this enormous effect with a weak anti-inflammatory drug, so
I said, 'Wow, what might happen with a real anti-inflammatory drug?' "
Ridker said. "We've done dozens of lipid-lowering trials and dozens of
hypertension trials, but we haven't done a single inflammation-reduction
trial. But now we have two, which is very exciting."
The Cardiovascular Inflammation Reduction Trial (CIRT), announced last week [1], will compare methotrexate,
given 10 to 20 mg weekly for three to four years, with placebo in about
7000 adults who have had an MI within the past five years, have type 2
diabetes or metabolic syndrome, and are already on a statin. The end
point will be a reduction in recurrent MI, stroke, and cardiovascular
death among stable post-MI patients with type 2 diabetes or metabolic
syndrome. Methotrexate is already widely available as generic drug
indicated for rheumatoid arthritis and also sometimes used in higher
doses to treat certain types of cancer.
Ridker and colleagues will begin site
selection for CIRT in November to begin patient recruitment in March
2013, but he has already begun to talk up the significance of the study.
"This is the most exciting new biology in the field," he said. "And
[the National Institutes of Health] NIH is trying to back what is the most important science."
Novartis is also betting that directly
attacking inflammation will make a big impact on cardiovascular events
in patients already on a statin. The company is backing the CANTOS trial of canakinumab (Ilaris), a high-affinity human monoclonal anti-human interleukin-1
(IL-1) antibody currently used for the treatment of IL-1-driven inflammatory diseases (cryopyrin-associated periodic syndrome).
(IL-1) antibody currently used for the treatment of IL-1-driven inflammatory diseases (cryopyrin-associated periodic syndrome).
The study will compare three doses of
canakinumab with placebo in about 17 200 stable post-MI patients with
elevated high-sensitivity CRP levels. The primary end point will be
first occurrence of a major adverse cardiovascular event, a composite of
cardiovascular-related death, nonfatal MI, and stroke over a follow-up
of three years. There will also be a substudy measuring the change from
baseline in the patients' carotid plaque burden in the bifurcation
region of the index carotid artery and another study measuring the
change from baseline of the patients' insulin secretion rate.
The study began in April 2011 and is expected to be completed in the summer of 2016.
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