Six months after the US Food and Drug Administration required cholesterol-lowering statin drugs to carry warnings about diabetes risks, Brigham and Women’s Hospital researchers conclude in a new analysis of a landmark study that the increased likelihood of diabetes is outweighed by the drugs’ protective effects against heart attacks, strokes, and heart disease deaths.
The new study, published Thursday in the journal Lancet, delved into findings from a 2008 clinical trial involving nearly 18,000 adults without heart disease or high cholesterol but with high levels of artery-damaging inflammation. That trial found a small increased diabetes risk among people who took rosuvastatin (Crestor). The new analysis shows that the bulk of the extra diabetes cases occurred in certain statin users: those already on the verge of getting the disease because of being obese or having an elevated blood sugar levels or resistance to the hormone insulin.
“We’re not seeing any excess risk in those who have normal blood sugar levels and no other risk factors for diabetes,” said study leader Dr. Paul Ridker, a Brigham cardiologist.
The original study, called Jupiter, and the followup analysis were funded by Crestor manufacturer AstraZeneca, and Ridker holds a patent on the test used in the trial to measure inflammation.
While statins have been shown to have life-saving benefits in patients already diagnosed with diabetes or in those who have had previous heart attacks, their use for preventing future heart attacks and strokes in healthier patients has come into question as diabetes risks have become more widely known. But the latest finding should provide reassurance to patients taking statins for the prevention of heart disease, said Dr. Allison Goldfine, head of clinical research at the Joslin Diabetes Center.
In patients at increased risk for diabetes, statins, when compared with a placebo, reduced the overall risk of dying or of having a heart attack, stroke, or other serious heart complication by 39 percent, the study found, while increasing the risk of developing diabetes by 28 percent.
In absolute terms, 134 vascular complications or deaths were avoided for every 54 new cases of diabetes diagnosed during the trial in these high-risk patients, who were followed for an average of two years. The researchers found that the increased diabetes risk applied only to those who were already on the threshold of developing the disease -- speeding up their time to diagnosis by about 5 weeks on average.
“Statins may bring on diabetes a little earlier, but the condition is manageable,” Goldfine added. “But the leading cause of death in diabetics is heart disease and that’s what statins help prevent.”
Despite the finding from the Jupiter trial that statins provided net benefits for those with an elevation in an inflammatory marker called C-reactive protein but not high cholesterol, doctors have been largely reluctant to prescribe the drugs solely on the basis of elevated CRP levels because of concerns about diabetes and other side effects, such as muscle aches and rare but serious kidney or liver complications.
While the latest finding may shift practices somewhat toward prescribing statins more frequently, some experts pointed out that the benefits are still very small in a population at low risk of having a heart attack.
“The study found only a marginal benefit for reducing major heart events, and it’s a narrow tradeoff with the increased diabetes risk,” said Dr. Eric Topol, a cardiologist at the Scripps Clinic in La Jolla, Calif. “It’s not an acceptable reason to give rosuvastatin to those whose only risk is a high CRP.”
One reasonable approach doctors can take, said Goldfine, would be to analyze a patient’s heart disease risk factors, including age and family history, and to get a CRP measurement in those with a moderately high risk of having a heart attack over the next 10 years. “The CRP test could be a very valuable part of the decision in determining whether these patients should be on a statin.”