RE:RE:RE:RE:RE:RE:Blood vessel damage "...almost half of heart attacks and strokes in the United States occurred in people who did not have high cholesterol."
"The idea that cardiovascular disease is an inflammatory condition is broadly accepted today. In the past several years, a handful of large clinical trials has refined the understanding of the pathways involved and brought new anti-inflammatory therapies for cardiovascular disease close to use in the clinic."
"CRP is tied, in particular, to a pathway that includes the signalling molecules interleukin (IL)-1β, IL-18 and IL-6, which, in the past few years, have emerged as key players in atherosclerosis."
Researchers are getting closer to reaping the therapeutic fruits of the many inflammation studies. Promising results over the past year from two placebo-controlled trials of colchicine, a drug used to treat arthritic conditions such as gout, “provide independent confirmation of what we saw in CANTOS”, Ridker says. Colchicine targets the same inflammatory pathway as canakinumab.
“We had a drug that was known to be safe, that has been around for more than a century, that was widely available, orally administered and cheap. So for us, it was the ideal agent to test,” says Jean-Claude Tardif, a cardiologist at the Montreal Heart Institute in Canada. Tardif led one of the two colchicine trials6, known as COLCOT (Colchicine Cardiovascular Outcomes Trial), involving 4,745 participants.
In COLCOT, colchicine resulted in a 23% reduction in future cardiac events or death; in a slightly larger trial7 called LoDoCo2 (Low-dose Colchicine 2), the reduction was 31%. In fact, a cost-effectiveness analysis of the COLCOT data showed that the drug was an exceedingly good deal. “Anytime you give colchicine to a patient who has recently had a heart attack, you actually decrease overall costs in the health-care system,” Tardif says.
Some cardiologists are already beginning to prescribe colchicine for certain people with cardiovascular disease. But researchers are also launching additional trials of colchicine and other anti-inflammatory drugs. Tardif is planning a study that will investigate the role of colchicine earlier in the disease process, testing whether the drug prevents a first heart attack in 10,000 people with type 2 diabetes.
At the American College of Cardiology meeting, held virtually in May, Ridker announced a phase III trial of ziltivekimab, a monoclonal antibody that targets IL-6; it is the first drug in its class to be developed specifically for cardiovascular disease. The trial will test ziltivekimab in 6,000 people with chronic kidney disease, a population that is at elevated risk of dying from heart attacks and strokes but that cannot take colchicine, which is processed by the kidneys.
Thirty years on from his radical proposal, Ridker still has a propensity to think big. He foresees a kind of grand unification approach emerging in which both lipids and inflammation are seen as essential elements to treating heart disease. “In the future, we’re going to bring these two things back together,” he says. “My belief is that the sum will be greater than the parts. If we could figure out an inexpensive, safe way to dramatically lower cholesterol and dramatically lower inflammation earlier in life, maybe we could actually eliminate this disease.”
Inflammation in heart disease: do researchers know enough? (nature.com)