CUT HEART ATTACK RISK EVEN WITH
cholesterol-lowering statin drugs have become one of the most commonly
prescribed classes of medications in the world, and nearly 20 million
have been prescribed statins in the
published prospective, randomized, placebo-controlled research study,
to as the JUPITER study, enrolled nearly 18,000 adults in the
There are several unique and clinically important aspects of this clinical study to be considered. First unlike many of the previously published clinical studies looking at statins, the JUPITER study included large numbers of women, African-Americans and Hispanics, and the study confirmed that all of these groups appeared to benefit from treatment with statin drugs. The other important difference in this study is that the volunteer patients participating in this clinical study all had normal total cholesterol and LDL cholesterol levels in their blood. However, these patients also had abnormally high levels of C-reactive protein (CRP) in their blood.
CRP is a protein that is manufactured primarily in the liver, and is a marker of both acute and chronic inflammation. Many cardiovascular disease experts believe that coronary artery disease, peripheral vascular disease and some types of stroke are all associated with chronic inflammation occurring within diseased blood vessels. CRP has been shown, in some research studies, to act as a marker for cardiovascular disease, especially in patients with elevated cholesterol levels (although elevated LDL cholesterol levels are thought to be more predictive of cardiovascular disease risk than elevated CRP levels).
In the JUPITER study, volunteer patients were randomized to receive either Crestor, a relatively new statin drug, or a placebo (sugar pill). Neither the patient volunteers nor the researchers knew which pill each patient was randomized to receive. (Randomized “double-blinded” prospective studies, such as this one, are generally accepted as the most accurate way of validating the effects of new treatments.)
At the point when this study was prematurely halted, the collected data revealed that the patients receiving the statin drug Crestor, when compared to the patients receiving a placebo, experienced a 55 percent reduction in the risk of heart attack and a 48 percent decrease in the risk of stroke. Overall, the risk of experiencing a major heart attack, stroke, or death from any cardiovascular disease was reduced by 47 percent in the group of volunteer patients who received Crestor. The patients who were randomized to receive Crestor experienced, on average, a 50 percent reduction in LDL cholesterol blood levels and a 37 percent reduction in CRP blood levels. It is very important to point out that the JUPITER study’s patient volunteers better represented the general population in terms of age, gender and race than most of the previously published statin studies, and all of these various subgroups of patients appeared to benefit equally from statin therapy.
The results of this study are likely to significantly change the existing guidelines for the use of statins in cardiovascular disease prevention, as many of the patients in the JUPITER trial who appeared to benefit from statin therapy would be considered, by current guidelines, to be at relatively low risk for cardiovascular disease (e.g., based upon their age, weight, smoking history, family history, cholesterol levels, and the presence or absence of high blood pressure). Indeed, many of the JUPITER study patients would not be candidates for statin medications under the current clinical guidelines for the use of these potent drugs.
At the present time, CRP is not routinely used to screen for cardiovascular disease in the asymptomatic population. Thus, this study raises the additional question as to whether or not CRP levels should be regularly measured, in addition to cholesterol and triglyceride levels, as part of routine cardiovascular disease screening. Certainly, the results of this study would suggest that CRP levels should probably be checked more frequently, particularly in patients who do not have other apparent risk factors for cardiovascular disease, such as advanced age, a history of smoking, obesity, diabetes, hypertension, sedentary lifestyle or elevated levels of total and LDL cholesterol. Based upon the entry criteria for the JUPITER study, men at or above the age of 50 and women at or above the age of 60 who have a CRP blood level greater than 2.0 milligrams per liter should at least be considered for statin therapy, even if their cholesterol levels are within the normal range. (It should also be noted that CRP levels can become elevated at any single point in time for a variety of reasons, including periods of acute illness and infection, and so single measurements of CRP may therefore not accurately reflect an individual’s risk of cardiovascular disease over the long-term.)
Whether or not everyone should be considered for statin therapy is unclear at this time, and another large scale prospective, randomized, placebo-controlled, double-blinded study, like the JUPITER study, will be necessary to answer this question. It should also be remembered that statins, like most drugs, are associated with a small but significant risk of potentially serious side effects. In a small percentage of patients, statin drugs have been associated with serious liver, muscle and kidney toxicity, and all patients who are started on statin drugs must be carefully followed by their physicians for any evidence of these potential complications of statin therapy.
Finally, it is important to note that this study was funded by the manufacturer of Crestor (AstraZeneca). As I have previously warned, clinical research studies that are conducted with funding from “interested parties” must always be viewed with a critical eye. As this is an increasingly more common phenomenon, however, as government sources of research funding continue to shrink, it has become impossible to simply reject the findings of all “industry-sponsored” research studies. In the case of the JUPITER study, the authors have filed disclosures indicating that AstraZeneca was completely excluded from all data collection and data analysis, and from the writing of the study’s soon-to-be published manuscript.
more than 1200 male veterans, all of whom were taking statin drugs for
LDL cholesterol, were followed between 1990 and 2006 at the
On average, LDL cholesterol levels decreased by 28 percent after beginning treatment with statin drugs. Interestingly, PSA levels also declined after these men began taking statins and, moreover, the greatest reductions in PSA levels were observed in the men who also had the largest reductions in their LDL cholesterol levels. Among the men who experienced the largest reduction in LDL cholesterol levels, after initiating statin therapy, a 17 percent reduction in blood PSA levels was observed.
Currently, the measurement of blood PSA levels is an important part of routine screening for prostate cancer, and elevated levels of this protein generally indicate the need to perform biopsies of the prostate gland to rule-out cancer. The results of this study, therefore, raise the concern that early cases of prostate cancer might conceivably be missed in men who are taking statins, as mildly-to-moderately elevated levels of PSA might be suppressed by long-term statin use. Whether or not statin-associated reductions in PSA levels might actually be associated with a lower risk of prostate cancer was beyond the scope of this study, and so further prospective randomized clinical trials with statin drugs and placebos must be completed before any claims can be made that statins reduce the risk of prostate cancer. For now, however, the results of this limited observational research study suggest the need for caution when interpreting PSA results in men who are taking statins. Certainly, men with a family history of prostate cancer (and at an early age, in particular), and African-American men, should advise their physicians about the results of this research study if they are currently taking statin drugs, and these high-risk men should be carefully monitored for other signs and symptoms of prostate cancer, in addition to PSA levels. In such cases, a low threshold to perform biopsies of the prostate gland should at least be considered.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
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Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
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