Interpreting JUPITER: Statins for Everyone?

It may be premature to reflexively prescribe the powerful drug to people with normal cholesterol.

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JUPITER, a heart attack and stroke prevention study led by Paul Ridker of Harvard, made a splash at the American Heart Association meetings in New Orleans on Sunday, leaving many experts convinced that it will change overnight how we practice preventive medicine. For men over 50 and women over 60, the results suggested, a blood test for C-reactive protein or CRP that signals low-grade inflammation in the body could dramatically reduce the risk of first time heart attacks, strokes, and other artery problems in apparently healthy people if an abnormal CRP level triggers continuous intensive statin therapy. In this study, the statin of choice was Crestor.

It sounds easy, if not breathtaking. But I'm inclined to line up with those who say, "slow down." Before doctors translate what are undoubtedly important scientific findings into an enthusiasm for placing 6 million people on a strong drug forever, JUPITER needs to provide further analysis of what on closer look is a highly varied group of patients carrying a wide range of health risks.

JUPITER's enrollees were 17,802 presumably healthy people who had higher than normal levels of inflammation. But most were not as healthy as they seemed, even if their levels of the bad LDL cholesterol were deemed normal. In fact, some were walking vasculopaths. And why not? After all, they were chosen for their abnormal CRP, the nonspecific inflammatory molecule that is known to be elevated in the elderly, the overweight, and those with other known heart risk factors.

As a result, the JUPITER trial was riddled with obesity, high blood pressure, prediabetes, and genes predisposing to heart disease. Almost 3,000 enrollees were smokers, a big time CRP elevator, and only 10 percent took aspirin, an inexpensive preventive medicine that protects against both heart disease and stroke. (Aspirin also lowers CRP.) Other study patients were really healthy, free of any known risk factors and yet had elevated CRP for no obvious reason.

To manage such a heterogeneous group reflexively with a single prescription for 20 mg of Crestor, the most powerful and perhaps expensive statin on the planet, is at odds with tailoring prevention programs to the needs of the individual patient.

Moreover, the most striking finding of JUPITER is just how low the daily 20 mg of Crestor took participants' LDL levels almost at once, with a sustained effect. In two years, half the patients had LDL cholesterol between 42 to 69 mg/liter, well below the normal level of 130 mg/liter and the optional target range of less than 100 mg/liter for people at moderate risk based on their risk factors. And a quarter of study patients had levels below 42. The long-term effect of this abnormally low level is simply unknown. Though over the years many have speculated about adverse side effects on blood clotting, hormones, brain function, and even cancer risk, the consensus among cardiologists is that the possibility of any of these is remote.

It's also worth pointing out that while LDL cholesterol, an inflammatory molecule, was cut in half by Crestor, CRP fell by a modest 37 percent from its elevated state, leaving most patients with still-high CRP levels. This again points to an ongoing controversy: Does lowering CRP levels have a direct heart benefit, or is it only a marker of lower levels of the toxic and inflammatory LDL that goes into plaque?

If you're healthy, the question to ask your doctor before starting on intensive therapy for prevention is just what your own personal risk of a heart attack or stroke might be. If you are truly healthy, and it boils down to a 1.5 percent chance of having a heart attack in the next 10 years, cutting the risk in half means 0.75 percent. In neither case are you likely to be in significant danger. Before swallowing the first pill, remember that that computes to improving the odds of not having a heart attack or stroke from 98.5 percent to 99.3 percent. The choice is yours.