Preventing Recurrent Blood Clots

Deep venous thrombosis (DVT) has been in the news after lawsuits were recently filed against several airline companies.  The lawsuits allege that airline companies failed to warn travelers about the risk of this complication arising from long periods of inactivity.  DVT is generally thought to occur when one or more of the following conditions exist:  decreased flow of blood through the veins, an abnormal predisposition of the blood to clot, or damage to the lining of the veins.  Typically, the large veins of the thighs and pelvis become acutely obstructed with blood clots when DVT occurs.  If DVT progresses, pieces of these clots can break off and travel to the lung, causing pulmonary embolism (PE), a condition that may result in life-threatening clogging of the arteries of the lungs.  Among hospitalized patients, PE is one of the most common causes of sudden unexpected death.  Even when PE does not occur, DVT can leave patients with permanent health problems, including chronic swelling and skin ulceration involving the affected extremities.  Moreover, patients with a prior history of DVT are at greater risk of developing another DVT than people without any history of DVT.

At least one-third of DVT cases do not appear to be associated with classic risk factors.  However, in the majority of cases, a history of severe illness, prolonged inactivity (particularly with the legs flexed or otherwise immobilized for long periods of time), cancer or other severe chronic illnesses, or a history of trauma or major surgery are present.  The standard treatment for DVT, with or without PE, involves the use of blood-thinning anticoagulant drugs for at least 6 months following the initial diagnosis.  While very effective in preventing further complications and recurrences of DVT and PE, the use of anticoagulant therapy is associated with an increased risk of bleeding events, and patients taking anticoagulant drugs must be carefully monitored to prevent both over-anticoagulation and under-anticoagulation.  Following completion of this 6-month anticoagulation regimen, patients are closely followed by their physicians for any evidence of DVT-related complications or recurrence.

A study in the current issue of the New England Journal of Medicine assessed the long-term use of low-dose anticoagulant therapy in patients with a previous history of DVT.  A total of 508 patients with a history of DVT entered the trial, and were randomized to receive either anticoagulant pills or a placebo (sugar pills).  The patients who were randomized to receive the anticoagulant drug Coumadin were maintained at a level of anticoagulation that was one-third to one-half the level that is generally achieved during the traditional 6-month post-DVT period of therapy.  The study was prematurely halted, after an average of 2 years follow-up, due to a dramatic reduction in the incidence of recurrent DVT among the patients receiving low-dose Coumadin.  The patients receiving the placebo pills had nearly 3 times the incidence of recurrent DVT when compared to the patients receiving the anticoagulant pills.  At the same time, the incidence of major bleeding complications among the two groups of patients was not statistically significant, nor was the death rate between the two groups significantly different during this relatively brief study. 

This study is the first randomized prospective well-controlled long-term anticoagulation trial performed on patients with prior DVT that I know of, and its findings strongly suggest that long-term low-dose anticoagulant therapy should probably become the standard of care for this illness.  The ideal duration of long-term therapy, and the minimally effective level of anticoagulation necessary to achieve significant reductions in DVT recurrence, however, are issues that were not addressed by this study.  These concerns will have to be resolved through additional research.  However, this study presents a compelling case for continuing anticoagulation therapy for more than 6 months following the diagnosis of DVT, albeit at a lower intensity than initial post-DVT therapy.

Aortic Valve Stenosis, Arteriograms & Strokes

The aortic valve is the largest valve in the heart, and functions to prevent the backflow of blood into the heart after it is pumped into the body’s largest artery, the aorta.  When this valve becomes narrowed, or “stenosed,” the heart has to work progressively harder to pump blood to the body’s organs and, in time, the heart will begin to fail if the abnormal valve is not repaired or replaced.  Abnormal collections of tissue and blood clots may also form on the damaged valve’s surface, and may break off and travel to the brain and other organs, sometimes with devastating consequences.  In most patients, the severity of aortic valve stenosis (AVS) can be accurately assessed using sound waves (echocardiogram).  However, many patients with known or suspected AVS will require heart catheterization to fully assess the condition of the aortic valve and the remaining heart structures.  Although cardiac angiography is associated with a small risk of stroke, secondary to displacing small bits of tissue and clots from damaged valves and arteries, the incidence of “silent strokes” due to heart catheterization for AVS is not known.

In the current issue of the British journal Lancet is an interesting study that prospectively randomized 152 consecutive patients with AVS to two different methods of cardiac catheterization.  A total of 101 patients underwent catheterization involving the passage of the catheter tip through the damaged aortic valve, which is typically performed during a comprehensive angiographic assessment for AVS.  The remaining 51 patients underwent cardiac catheterization, but the catheter was not advanced through the damaged aortic valves of the study volunteers.  A third group of 32 patients were included in the study as control patients.  These control patients underwent cardiac catheterization for non-AVS heart conditions.  All study patients underwent MRI scans of the brain and neurological examinations both before and after their heart catheterization procedures. 

Among the 101 patients who underwent catheterization with passage of the angiogram catheter through the aortic valve, 22 (22%) developed evidence of small strokes on their brain MRI scans following their angiograms.  Three of these patients (3%) had clinically significant neurological findings consistent with small strokes.  In contrast, none of the patients who underwent heart catheterization without passage of the catheter through the aortic valve, including the control patients, went on to develop either MRI or clinical evidence of stroke. 

This is a very powerful and informative study, and it provides hard data on the incidence of both clinically significant and subclinical stroke incidence following catheterization of stenotic aortic valves.  The 22% incidence of subclinical stroke that was identified in this study is much higher than most experts might have predicted following aortic valve catheterization for AVS.  Whether or not patients who developed clinically silent strokes after their catheterization procedures will go on to develop clinical symptoms of brain dysfunction as they age, and as their brains are subjected to additional insults from surgery or disease, is not clear.  The patients in this study should, therefore, be longitudinally studied in an effort to determine how many patients with “silent strokes” will actually go on to manifest symptoms from these small brain injuries.  Meanwhile, it would appear that catheterization of the aortic valve should be avoided whenever possible in patients with known or suspected AVS.

Obesity Update

We are, quite bluntly, the fattest nation in the history of the world.  More than half of us are overweight, perhaps a quarter of us are clinically obese, and the incidence of obesity and diabetes among our children has reached historic levels.  Inexpensive calorie-dense diets, a plethora of effort-saving devices, and a nearly universal aversion to aerobic exercise are all commonly cited etiologic factors for this epidemic of obesity in the United States, and in many developed countries as well.

Two studies in the current issue of the Journal of the American Medical Association (JAMA) shed additional light on the topic of obesity.  The first study examined the relationship between prolonged television (TV) watching and the risks of obesity and adult-onset diabetes among 50,277 women participating in the landmark Nurses’ Health Study.  This prospective study was conducted between 1992 and 1998, and has yielded a wealth of public health data to date.  The women who participated in this study did not meet the criteria for clinical obesity upon entering the study, and none of them had diabetes.  However, during the 6-year study period, nearly 8% of the women subsequently became clinically obese, and 3% of the 50,277 women developed new onset of adult diabetes.  Time spent watching TV was significantly associated with the development of both obesity and diabetes.  After adjusting for confounding factors (such as age, smoking, exercise levels, diet and other relevant factors), the study authors found that each 2 hour per day increment of TV watching was associated with a 23% increase in the risk of obesity and a 14% increase in the risk of diabetes.  In the workplace, each 2 hour per day increment of sitting raised the risk of obesity by 5%, and the risk of diabetes by 7%.  Conversely, each 2 hour per day increment of standing or walking at home resulted in a 9% decrease in the risk of obesity, and a 9% decrease in the risk of diabetes.  Each one hour per day increment of brisk walking was associated with a 24% reduction in the risk of obesity, and a 12% risk reduction for diabetes.  After statistical analysis of their results, the authors concluded that 30% of the new cases of obesity and 43% of the new cases of diabetes could have been entirely prevented by adopting a more active lifestyle, which they defined as, minimally, less than 10 hours of TV watching per day and at least 30 minutes of brisk walking per day.

This study reaffirms the findings of other recent studies, of both adults and children, that even relatively modest levels of regular physical activity are associated with a dramatic reduction in the risk of obesity, diabetes and cardiovascular disease.  As with the other studies, it is almost shocking how little physical exertion is required to make such a big difference in overall health.  While a small percentage of obese people will be found to have some underlying medical condition that predisposes them to becoming overweight, large scale studies such as the Nurses’ Health Study confirm the traditional clinical perspective regarding the causes of obesity:  too much eating and not enough exercise.  And, yet, the scale-busting average weight of Americans continues to rise each year.  Food for thought, I suppose….

The second JAMA study looked at the impact of Internet-based weight loss programs on long-term weight loss.  The study compared online weight programs with and without E-mail-based counseling.  A total of 92 obese adults participated in this study between September 2001 and September 2002.  The study found that, at one year, the 46 patients who received ongoing counseling via E-mail had lost an average of 9.7 pounds, while the study participants who completed the weight loss program without ongoing counseling had lost an average of only 4.4 pounds at one year.  The authors concluded that the addition of counseling, via E-mail, to Internet-based weight loss programs results in the maintenance of greater weight loss at one year than programs without E-mail counseling.  This result is in keeping with other research that confirms the high recidivism rate associated with weight loss programs that do not provide significant ongoing support to overweight participants.

Echinacacea & Quality Control

Regular readers of this column already know that non-prescription herbal remedies and “nutritional supplements” are not subject to the same rigid potency and purity regulations that the Food & Drug Administration (FDA) applies to prescription and non-prescription pharmacologic medications.  Indeed, no scientific evidence of efficacy is required for non-prescription supplements, as is required for all prescription and over-the-counter medications.  An interesting little study in the Archives of Internal Medicine sheds some light on the untidy reality of this disparate regulation of nonpharmaceutical remedies.

Echinacacea sales represent almost 10% of the supplement market in the United States and, thus, this supplement is probably representative of many of the products sold in this category.  The authors collected 59 different Echinacacea-only supplements at various retail stores throughout Denver.  They then measured each preparation for content and purity using a method known as thin layer chromatography.  Of the 59 samples, 6 (10%) contained no measurable Echinacacea at all!    Less than one-third of the supplements contained the indicated number of milligrams of Echinacacea in each capsule or tablet.  Among the 59 samples, only 21% were labeled as “standardized,” suggesting that lot-to-lot Echinacacea content was carefully controlled by the manufacturer.  Among these 21 standardized samples, less than half (43%) met the labels’ standards.

Quite apart from the critical issue of supplement efficacy, this study raises disturbing questions about the quality control measures in use by manufacturers of dietary supplements, and manufacturers of Echinacacea in particular.  This study adds weight to the growing outcry for closer scrutiny and regulation of dietary supplement manufacturers by the FDA, and raises serious potential questions about the ethics of some of these manufacturers, and the quality of their products.

Dr. Robert A. Wascher