AstraZeneca’s drug Crestor lowers the risk of heart attacks in apparently healthy adults with no prior history of cardiac disease and normal cholesterol levels, according to the results of a trial known as Jupiter.
Participants in Jupiter did have elevated levels of C-reactive protein (CRP), a non-specific marker for inflammation that identifies people at risk for cardiac events regardless of their cholesterol levels. CRP levels are measured using a $20 dollar blood test that is covered by most insurance policies.
Jupiter was a multicenter, prospective trial involving 17,802 participants in 26 countries that had entered an age where cardiac risk is highest—men over 50 and women over 60. Participants had no signs or symptoms of cardiac disease, and their cholesterol levels were not high enough to prompt treatment using current guidelines. But their CRP levels were high—at least 2.0 milligrams/liter.
Participants were randomized to receive 20 milligrams of Crestor or a placebo. Those who took Crestor experienced a 54% reduction in the risk of heart attack and a 48% reduction in the risk of stroke. They were 46% less likely to require angioplasty or coronary bypass surgery and had 20% lower mortality from all causes. LDL (bad) cholesterol dropped 50% and CRP levels dropped 37% in the Crestor group. Serious adverse events were rare and occurred at the same rate in both groups.
Paul Ridker, a cardiologist at Brigham and Women’s Hospital, was the principal investigator of the Jupiter trial. He presented the results in New Orleans yesterday during a meeting of the American Heart Association. Ridker is listed as an inventor on several CRP assays whose patents are held by the Brigham. He and several co-authors receive grants and other income from AstraZeneca.
“The potential public health benefits are huge,” Ridker told the Washington Post. “It really changes the way we have to think about prevention of heart attack and stroke.” Ridker’s point seems well taken since nearly half of all heart attacks occur in people that have normal cholesterol levels. JUPITER suggests a broader screening role for CRP, especially in those with normal cholesterol.
However, Stanford cardiologist Mark Hlatky expressed caution to the Wall Street Journal. “Before we expand treatment indications in any drastic way, we need to do due diligence,” he said. “The idea that everybody should get CRP measured is premature and not backed up by good data.”
But Hlatky’s cautionary note was largely overwhelmed by positive buzz at the New Orleans Convention Center. “These are very, very dramatic findings,” commented Elizabeth G. Nabel, Director of the National Heart, Lung and Blood Institute. “This really validates inflammation as being an important factor in the development and progression of heart disease, and that treating inflammation, even in the setting of a normal cholesterol level, may be very important for certain individuals.”
The results of Jupiter could dramatically increase the $15 billion market for cholesterol-lowering statins, already the world’s best-selling drugs. AstraZeneca’s Crestor captures 9% of the market right now. Pfizer’s Lipitor (27%) and generic statins (49%) have the lion’s share of the market at the moment.
Both Lipitor and the generic simvastatin have been shown to lower LDL cholesterol and CRP levels.