Crestor cuts heart attack and stroke rates even if cholesterol is normal
November 11th, 2008
A recent study called JUPITER, using the statin, rosuvastatin (Crestor), has shown a substantial improvement in the risk of heart attack and stroke in people even if their cholesterol levels are normal. At present, people are recommended to take a statin only if they have already had heart disease, or have elevated cholesterol, high blood pressure or diabetes. Specialist clinics, as here at London Medical, will assess a patient’s risk in greater detail using further analysis of the lipoproteins that make up the cholesterol value (measuring “good” and “bad” lipoproteins), with intima media imaging of the common carotid arteries and a coronary artery calcification score. Using such methods, people who have increased heart disease risk can be identified even if their total cholesterol is normal.
One of the tests used is the high sensitivity C reactive protein (hs CRP), a general marker for inflammation. For some years now, low grade inflammation has been thought to contribute significantly to arterial inflammation and the Metabolic Syndrome (the cluster of risk factors that include central fat distribution, diabetes with insulin resistance, hypertension and abnormal cholesterol profile). The Jupiter trial used this marker for the risk of future heart disease, instead of cholesterol, in identifying the population that may respond to the statin, Crestor (rosuvastatin). CRP responds to treatment with statins and the question was whether it also led to real life reductions in heart attack and stroke rate.
18,000 people participated in the study with 8,901 people given 20 mg rosuvastatin and a similar number a placebo. They were healthy and all had a total cholesterol of less than 3.5 mm/l but did have a raised hs CRP of >2 mg/dl. Rosuvastatin treatment reduced LDL cholesterol from 2.9 mm/l to 1.5 mm/l and hs CRP from 4.2 to 2.2 mg/dl. This was associated with a significant 44% reduction in the primary outcome of heart attack, stroke, unstable angina, need for angioplasty or death from cardiovascular causes or from all causes. The results were so clear cut and significant that the trial was stopped early.
So how will this change current practice? It is clear that a raised total cholesterol does not identify all patients at risk of a heart attack, nor does a raised cholesterol (especially in women with a high level of the protective HDL cholesterol) necessarily mean an increased risk. The combination of an unelevated cholesterol and raised hs CRP would lead to most people in the population requiring treatment, particularly as hs CRP should only be measured in the absence of minor intercurrent illness or inflammation, which can also raise the hs CRP.
We still believe that other tests, including hs CRP and other risk factors with non invasive imaging, should be used in a global assessment of risk so that patients are treated according to risk. But the result of the JUPITER study is a landmark trial, heralding for the first time, the powerful anti-inflammatory benefit of rosuvastatin (Crestor) in changing heart attack, stroke and mortality rate in normal healthy people without a raised cholesterol.
Dr Abraham, Nov 11th 2008
