ESC 2015: Dose lowering inflammation lower vascular risk? Paul Ridker M.D HD

Paul M. Ridker, M.D., talks to Cardio Debate about his presentation at the ESC 2015 that examines whether lowering inflammation lowers vascular risk. “We know that lowering cholesterol profoundly lowers event rates. The question is, is the residual risk our patients have driven by cholesterol, or is it also driven by this inflammatory response?” For more in-depth insight and analysis on issues in cardiology visit the Cardio Debate website: www.cardio-debate.com TRANSCRIPT For the past 25 years we’ve been trying to figure out a way, clinically, to address whether lowing inflammation par se will lower cardiac event rates. We showed many years ago that markers of inflammation predict risk, and then we showed that statin drugs lower both inflammation and cholesterol. Then we did our very large-scale JUPITER trial – 18,000 patients around the world showing that if you select people because they have a high inflammatory burden and then give them a cholesterol-lowering drug, they have far fewer event rates. But that trial looked at a lipid-lowering drug that has anti-inflammatory effects. So the next stage has been, can we focus down to agents that have pure anti-inflammatory effects that do not affect cholesterol at all? So we have two trials that are ongoing, one – funded by the United States National Heart, Lung and Blood Institute – is looking at a very commonly used drug, methotrexate, that millions of people take to treat their rheumatoid arthritis. It’s the standard of treatment for rheumatoid arthritis around the world. That drug happens to lower event rates people with in rheumatoid arthritis. So the question now becomes can we in people who don’t have obvious inflammation do that? So that’s the Cardiovascular Inflammation Reduction Trial. It takes post-myocardial infarction patients and randomly allocates them to aggressive care plus placebo, or aggressive care plus this upstream anti-inflammatory drug. Now while that’s an exciting trial, it is using a diffuse broad-spectrum anti-inflammatory agent. So we also wanted a second swing of the bat, to look at a narrowly targeted piece of the puzzle. And this is to do with interleukin-1 Beta. Interleukin-1 is the primary cytokine, it sits upstream from IL-6. IL-6 of course triggers the liver to put out CRP. So we think this is a very focused way of looking at the question. And that drug is Canakinumab which is manufactured by Novartis. It is in use for some very rare genetic disorders. What we are doing with colleagues around the world, we already have more than 10,000 patients randomized to this drug or a placebo, who have already had a heart attack, or who are on high dose statins. It’s an exciting time for this field. Cardio Debate: What are the main challenges? Some of the challenges we face are intellectual. As internists, as cardiologists we have grown up with the lipid hypothesis – and this is not about the lipid hypothesis directly. We know that lowering cholesterol profoundly l