HEALTH FOR LIFE

The Power of Statins

A new study supports the effectiveness of a drug treatment, and prompts a Harvard cardiologist to change the way he practices medicine.

 

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By now, virtually everyone who owns a television knows how heart attacks happen, or thinks they do: an excess of cholesterol, especially the kind called LDL (low-density lipoprotein) leaves deposits of plaque on artery walls, narrowing the passage for bloodflow until a clot comes along to block it entirely. This concept led to the development of cholesterol-lowering statins, such as Mevacor (lovastatin), Zocor (simvastatin), Pravachol (pravastatin), Lipitor, Lescol and Crestor. Increasingly, however, researchers are focusing on another culprit that also plays a key role: inflammation, which can make artery plaques rupture, very often the trigger that turns artherosclerosis into a heart attack.

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Now a large international study (the JUPITER trial) lends support to that idea and also shows that the same statins that control cholesterol also act to reduce inflammation. (Strictly speaking, the trial only tested one such drug, Crestor, whose manufacturer, AstraZeneca, paid for the study.) JUPITER included nearly 18,000 seemingly healthy volunteers in prime heart-attack age—men age 50 and over, women age 60 and older. While their LDL cholesterol levels were healthy, the volunteers all had above-normal levels of C-reactive protein, or CRP, a sign of inflammation. (Normal CRP is below 1 milligram per liter; the volunteers all showed levels above 2.) Half of the volunteers took a daily 20mg tablet of Crestor; the rest took a placebo. LDL cholesterol levels dropped by roughly half and the CRP levels dropped by about a third in the statin group. In the placebo group, LDL and CRP levels didn't budge.

Even more impressive, there were about 50 percent fewer heart attacks and strokes in the statin group than in the placebo group. Unlike many earlier trials using statins, JUPITER included a large number of women, Hispanics, and blacks. Each of these groups benefited from statin therapy as much as white men.

JUPITER has changed my thinking about the high-sensitivity CRP test and about when to prescribe statins. Like many cardiologists across the country, I am now recommending the test more often. (The hospital in which I work receives patent revenue from the test, but I do not.) The CRP test is not for everyone, though. If someone already has been diagnosed with heart disease, the test adds little or no useful information, because the implications for treatment aren't clear yet. The same is true for those at very low risk—people younger than the volunteers in the JUPITER study, without other risk factors for heart disease.

The test is most useful for people in the middle of the risk curve. A high CRP level is a factor that may weigh on the side of starting statin therapy; a low reading may be taken by some as an indication it's not needed. How do you know where you stand? Risk tools such as the Framingham score and Your Disease Risk estimate your chances of having a heart attack in the next 10 years. (For links to these tools, go to health.harvard.edu/newsweek.) There are other considerations. Statins are expensive—a year's supply of Crestor or one of its competitors can cost more than $1,500. And although millions of people take them safely, they can cause pain in some people, and in rare cases muscle damage and, possibly, memory loss. To put the numbers from the JUPITER study into perspective, during the two-year trial, 1.5 percent of the participants who were taking the placebo had a heart attack or stroke, compared with 0.7 percent of those taking Crestor. That means 25 people would have to take a statin for five years to prevent one cardiovascular event. As treatments go, that's not bad, but it doesn't mean we should be putting statins in the water supply.

There are other ways you can fight inflammation than by taking a statin: If you smoke, stop. If you are overweight, shed some pounds. Adopt a Mediterranean-style diet based on fruits, vegetables, whole grains, nuts, and olive oil. Eat more fatty fish. Exercise almost every day. Get enough sleep. Reduce stress.

If you have heart disease or are at high risk for it, taking a statin and adopting healthful lifestyle changes make sense, even if your LDL is in the normal range. If you are a man age 50 or greater, or a woman age 60 or greater, and you are healthy but have a high CRP, the JUPITER results suggest you could benefit from the same strategy.

In 2009, researchers will be testing other ways to detect inflammation besides CRP, and developing genetic tests that may be more accurate predictors of heart-attack risk than the tools now in use. New drugs against inflammation are also in the works. The best approach, though, is something available to everyone today—living well to prevent atherosclerosis from ever taking hold.

Lee is associate editor of the Harvard Heart Letter and a cardiologist at Brigham and Women ' s Hospital and Harvard Medical School. For more information, go to health.harvard.edu/newsweek.

© 2008

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Member Comments

  • Posted By: quiact @ 12/21/2008 1:14:22 PM

    Facts Believed to be Associated With All Statin Medications:

    Adverse events associated with the statin class of pharmaceuticals are thought to occur more often than they are reported- with high doses of statins prescribed to patients in particular. However, ince this class of drugs has existed for use for over 20 years, statins are considered safe and effective for enhancing the clearance of LDL noted to be elevated in the lipid profiles of patients.
    Additionally, there is no reduction in cardiovascular morbidity or mortality, as well as an increase in a person???s lifespan, if one is on any particular statin medication for their lipid management over another, others have concluded. So caution should perhaps be considered if one chooses to prescribe such a drug for a patient if they are absent of dyslipidemia to a significant degree, or are under the belief that one statin medication provides a greater cardiovascular benefit over another. In other words, the health care provider should be assured that any statin therapy for their patients is considered reasonable and necessary if the LDL in their patients need to be reduced perhaps at this time with the evidence that exists regarding statins.
    Abstract etiologies for those who choose to prescribe statin drugs on occasion for reasons not indicated by these statin drugs- such as reducing CRP levels, or for Alzheimer???s treatment, or anything else not involved with LDL reduction may not appropriate prophylaxis at this point for any patient. All other benefits that appear to have favorable effects in such areas are speculative at this point, and require further research for disease states aside from dyslipidemia, according to many.
    .
    Yet overall, the existing cholesterol lowering recommendations or guidelines should be re-evaluated, as they may be over-exaggerated upon tacit suggestions from the makers of statins to those who create these current lipid lowering guidelines. This is notable if one chooses to compare these cholesterol guidelines with others in the past. The cholesterol guidelines that exist now are considered by many health care providers and experts to be rather unreasonable, unnecessary, and possibly detrimental to a patient???s health, according to others. Yet statins are beneficial medications for those many people that exist with elevated LDL levels that can cause cardiovascular events to occur because of this abnormality. What that ideal LDL level is may have yet to be empirically determined.
    Finally, a focus on children and their lifestyles should be amplified so their arteries do not become those of one who is middle-aged, and this may prevent them from being candidates for statin therapy now and in the future, regarding the high cholesterol issue.
    Dietary management should be the first consideration in regards to correcting lipid dysfunctions,

    Dan Abshear

  • Posted By: steveparkermd @ 12/09/2008 12:24:38 PM

    Astra-Zeneca has a powerful marketing machine touting this study. As andy256 points out, the results are not as dramatic as reported in the news releases. For details, please see my healthy lifestyle blog post: http://advancedmediterraneandiet.com/blog/?p=88
    ---------Steve Parker, M.D.

  • Posted By: andy256 @ 12/07/2008 5:09:53 AM

    The NNT noted in the article does not reflect the NNT in the editorial in the NEJM authored by Dr. Mark Hlatky. Dr. Hlatky notes the following statistics:
    "The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin group; thus, 120 participants were treated for 1.9 years to prevent one event."
    http://content.nejm.org/cgi/content/full/NEJMe0808320
    I am puzzled by the incredible differences in the statistics reported between these two articles. A NNT of 25 is very different from an NNT of 120--yes, I do know that the first NNT is for 1 yr and the 2nd reported for 1.9 yrsyrs. The revised NNT for the editorial would be 61 for 1 year, not 25. How does your author arrive at this "new" and improved number?
    And the participants had a mean BMI of 28.3; these were hardly "normal" individuals.
    Again, reporting that 50% of the Crestor group had fewer heart attacks and strokes is disingenuous. PLEASE provide the Absolute Risk numbers--Not the Relative risk. In this study the rate of cardiovascular incidents fell from 2.8% to 1.6 % with a statin. And the heart attack and strokes decreased from 1.8% to 0.9%. This difference: 1.8% equals 157 of 8901 participants in the placebo group vs 0.9% which equals 83 of the 8901 participants in the Crestor group , thus the touted "50% decrease in events". What this means in terms of NNT is that 120 participants were treated for 1.9 years to prevent one "hard" event.
    Neither of these decreases equal a true "50% decrease", as in 50% of subjects received benefit. Reporting the Relative Risk Numbers is misleading.
    In addition, Dr. Lee does not note the significant increase in diabetes in the Crestor group: 3.0%, vs. 2.4% in the placebo group; P=0.01. One wonders if the study had completed its scheduled 4 years what the incidence of diabetes would have been, as well as the absolute risks of cardiovascular events. .

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