Last Updated:  05/03/2009

The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author.  Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.

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STATIN DRUGS & BLOOD CLOTS (THROMBOEMBOLISM)

As I’ve mentioned in previous columns, the statin class of cholesterol-lowering drugs have revolutionized the management of elevated cholesterol levels, and have been shown, by multiple clinical studies, to significantly decrease the incidence of serious cardiovascular events, including fatal heart attacks (myocardial infarction) and strokes. 

The statins were originally developed for their ability to block a key enzyme required for the body’s synthesis of cholesterol.  Thus, the statins decrease total cholesterol levels in the blood and, most importantly, they specifically reduce LDL (the “bad cholesterol”) levels.   Numerous clinical research studies have shown that statin drugs reduce the risk of heart disease and heart attacks in patients with elevated cholesterol levels.  Additional research has also strongly suggested that statins can also reduce the risk of cardiovascular disease even in patients with normal cholesterol levels.  More recently, additional research into the biochemical function of these powerful drugs has also revealed other mechanisms of action in addition to their known direct effects on cholesterol synthesis and metabolism.  One of the most clinically important additional mechanisms of action of statins appears to be their ability to reduce inflammation throughout the body.  These anti-inflammatory effects have been linked not only to the statins’ ability to reduce cardiovascular disease, but also to their ability to potentially reduce the risk of stroke and, perhaps, even the risk of some cancers, as well.  However, the data supporting these additional potential benefits of statins has been less convincing than that for cardiovascular disease reduction.  I should also stress that not all claims currently being made for statins are likely to turn out to be true, and that, as with all medications, statins have been associated with potentially serious side effects (most notably, injury to the liver and to muscle tissue).  However, as I have observed before, it is difficult to think of any other recently developed class of medications that have accumulated a more impressive reputation for preventing life-threatening diseases than the statins (not surprisingly, the statin class of drugs remain the most commonly prescribed class of medications in the United States).

The good news regarding the potential beneficial health effects of statin drugs continues to roll in.  For example, in recent weeks, clinical research data has been presented suggesting that statins may reduce the risk of prostate cancer, and may also be able to slow the growth of tumors in men who already have prostate cancer (it should be noted, however, once again, that there have been conflicting research results published, thus far, regarding the ability of statin drugs to reduce cancer risks, and to shrink tumors in patients who already have cancer).  

This week, another important new clinical research study on statin drugs has just been published.  In this new study, which appears in the New England Journal of Medicine, the potential effects of statin drugs in preventing blood clots of the veins was assessed in a huge randomized, placebo-controlled, double-blind, prospective clinical research trial.  Nearly 18,000 clinically healthy men and women participated in this very important clinical research trial.  All participants in this study had normal LDL cholesterol levels, but they also all had elevated levels of C-Reactive Protein (CRP), a protein in the blood that is associated both with chronic inflammation and an elevated risk of cardiovascular disease.  These 17,802 patient volunteers were randomized to receive either a statin pill (rosuvastatin, 20 milligrams per day) or an identical placebo pill (sugar pill).  This huge group of patients were then followed, for as long as 5 years, and were observed for evidence of blood clot formation within the large veins of the body (deep venous thrombosis), as well as the presence of blood clots that had migrated to the veins of the lungs (pulmonary embolism).  The results of this study, as I will discuss shortly, were quite remarkable.

Venous thromboembolic (VTE) disorders are a major cause of disability and death throughout the world.  Deep venous thrombosis (DVT) results when blood clots form within the deep veins of the body (most commonly within the large veins of the legs and pelvis).  A variety of conditions and circumstances can lead to DVT formation.  These include decreased blood flow, or “stasis,” involving the body’s deep veins, injury or inflammation of the internal surfaces (endothelium) of these veins, and any underlying health condition that increases the blood’s tendency to form blood clots (hypercoagulable state).  Pulmonary embolism (PE) is a potentially life-threatening condition, and most commonly arises in patients who have already developed DVT (PE occurs when chunks of DVT-associated clots break away and travel to the lung).  When the lung’s circulation becomes clogged-up with these itinerant clots (emboli), patients may experience shortness of breath, chest pain, or in serious cases of PE, complete cardiovascular collapse and death. 

VTE remains an underappreciated cause of serious illness, disability, and death.  Patients with severe or repeated cases of DVT often develop chronic swelling, pain, and skin damage of the affected extremities, due to the progressive destruction of the one-way valves in the large veins of the lower body that help to prevent pooling of blood in these dependent areas of the body (post-thrombotic syndrome).  Patients who survive significant PEs may also go on to develop permanent damage to the venous circulation of the lungs, leaving them with decreased blood flow to the lungs (pulmonary hypertension) and, in severe cases, chronic shortness of breath, lung injury, and heart damage (PE also remains the most common cause of unexpected death in hospitalized patients).  An estimated 900,000 new cases of VTE occur in the United States every year, and as many as one-third of these cases of VTE are fatal, which makes VTE a more common cause of death than either heart attacks or strokes!  As these statistics suggest, VTE remains a very serious public health problem in the United States, and throughout much of the world, as well.

In view of the seriousness of VTE as a public health problem, the findings of this newly published statin study are potentially very significant.  Among the 17,802 patients who participated in this prospective clinical trial, a total of 94 patients developed VTE, with 60 cases occurring in the placebo group and only 34 cases occurring in the statin group.  This represents a nearly 45 percent overall reduction in the risk of VTE associated with the daily use of the statin drug rosuvastatin.  When the researchers looked at potential risk factors for VTE among these 94 patients, additional important information was discovered, as well.  Among patients with known VTE risk factors (including cancer, recent major trauma, recent major surgery, or hospitalization for other reasons), the use of a statin drug reduced the risk of VTE by nearly 50 percent.  Among patients without any known risk factors for VTE, the daily use of rosuvastatin reduced the risk of VTE by about 40 percent.  When looking specifically of the risk of PE, the statin group of patients experienced a 23 percent risk reduction for PE, while the risk of DVT, specifically, was reduced by a whopping 55 percent in the statin group. 

The results of this study are quite remarkable, and they suggest that daily statin use may reduce the risk of VTE by nearly 50 percent, especially in people who are already at increased risk for VTE (whether or not all of the currently available statin drugs can provide VTE protection equivalent to rosuvastatin is unknown at this time, although all high-activity statins should, in theory, provide comparable protection).  This highly significant VTE prevention effect is, of course, a potential “health bonus” in addition to the cardiovascular disease reduction effect that statin drugs were originally designed for.  If you fall into a high-risk category for VTE, and you also have coexisting risk factors for cardiovascular disease, then you should certainly discuss statin drug therapy with your primary physician, based upon the findings of this pivotal clinical research trial.
 

Disclaimer:  As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity

 

Dr. Wascher is an oncologic surgeon, a professor of surgery, a widely published author, and the Physician-in-Chief for Surgical Oncology at the Kaiser Permanente healthcare system in Orange County, California

  

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