Aspirin and Disease Prevention

AspirinRecently the New York Times ran an op-ed entitled “The 2,000-Year-Old Wonder Drug” extolling the benefits of aspirin for a number of illnesses including cardiovascular disease and cancer. Although quite enthused about aspirin as a disease preventive, the author does advise medical consultation about the risks versus the benefits.

Is aspirin usually a good idea for middle-aged American? For those with known cardiovascular disease it usually is. However, one year ago a large study in the Archives of Internal Medicine did not show a reduction in cardiovascular or cancer deaths in patients without prior cardiovascular disease taking low-dose aspirin. A reduction in non-fatal heart attacks was noted. This benefit, however, was associated with a 30% increased risk of significant bleeding. The authors conclude against the routine use of aspirin for patients at low risk for cardiovascular disease.

More concerning, than the well-known risk of bleeding from the stomach or intestines, is the possibility of bleeding in the brain. Although the absolute risk of intracranial vessel bleeding is small (two hemorrhagic strokes per 10,000 patients taking aspirin) the consequences can be devastating.

Also, does aspirin prevent cancer? The evidence suggests that it is effective in preventing colon cancer and might be effective in preventing other cancers, although the evidence for the latter is less clear. The dose necessary to produce a statistically significant reduction in colon cancer is not certain, but some suggest that a full aspirin (325 mg) rather than low-dose aspirin (81 mg) might be needed.

The increased risk of bleeding associated with any dose of aspirin, and the possibility of greater risk with a higher dose, along with the very useful colon cancer prevention strategy of colonoscopy now in place caused the American Cancer Society not to recommend the routine use of daily aspirin to prevent colon cancer.

Patients at low risk for cardiovascular disease should consult their doctor before committing to a lifetime of daily low-dose aspirin. Low risk is defined as a patient whose 10-year absolute risk of a first coronary disease event is less than 10%. The doctor can calculate the risk by using a formula derived from the Framingham study of cardiovascular disease.

Aspirin is the wonder drug touted in the New York Times but, as usual in medical matters, every situation is different.

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Zithromax and Sudden Death

A recent study in the New England Journal of Medicine described an increased risk of death from cardiovascular causes in patients taking azithromycin. Azithromycin (Z-pack, Zithromax) is a very commonly used antibiotic and this warning merits concern.

The increased risk of cardiac death relates to the tendency of azithromycin to increase the risk of an irregular heartbeat. In this study a similar risk of increased cardiac death was noted in patients who took levofloxacin but not in patients who took amoxicillin.

The increased risk was small (47 additional deaths per 1,000,000 courses of treatment) and largely limited to patients with very significant heart problems. This increased risk is probably significantly less than that which had been noted with erythromycin in the past.

Since vulnerability is limited mostly to patients with significant heart problems (the top 10% severity of heart disease in this study) and, presumably, patients taking a number of cardiac medications some caution is needed when prescribing to these patients. Since the blood concentration of azithromycin causes the problem, particular caution is needed in patients with very severe heart disease who are also taking cardiac medications that will raise the blood concentration of azithromycin such as diltiazem and verapamil.

Sinus Fatigue

A little less than 10 years ago a research project that I had been working on for many years was published in the Archives of Internal Medicine. The observation that propelled me into the relationship described in the article related to my first experiences as a clinician.

I was aware that sinusitis caused fatigue years before I became a doctor because of personal experience and conversations with others who also suffered from sinus problems. I was surprised that my own doctor seemed unaware of the association and I was surprised that fatigue was not listed as a symptom in the general medical texts that I searched in college.

Nothing changed in medical school. Although the lists of illnesses that caused fatigue was quite long, and the lectures on the subject quite thorough, no one that I can recall mentioned sinusitis as a cause of fatigue.

When I first started practice my experience confirmed my own observations that patients with sinusitis were fatigued but, again, a thorough search of the medical literature produced nothing. I then started noticing that patients with a primary complaint of fatigue often, on more detailed questioning, acknowledged sinus symptoms but considered the sinus issue quite minor compared to the more pressing complaint of fatigue.

After trying to redirect the focus towards the sinus issue and initiating treatment, patients would usually notice a great improvement in fatigue. Patients found this puzzling. In fact, often a patient would return months later with the primary complaint of serious fatigue completely having forgotten the link with sinusitis. Once again I would treat the sinusitis and the fatigue would remit.

In the late 1980s I began to see some notice in the medical literature. A consensus conference of ear, nose and throat physicians in 1987 described fatigue as one of the diagnostic criteria for making the diagnosis of chronic sinusitis. I reported several cases of patients diagnosed as having chronic fatigue syndrome who experienced a complete or nearly complete resolution of fatigue following sinus surgery.

Nothing on the subject was mentioned in the internal medicine literature, an unfortunate omission since internists are the doctors who treat fatigue.

I was curious about how common sinus problems are found in patients with a primary complaint of unexplained chronic fatigue. This is how the project unfolded.

I examined 297 consecutive patients who were younger than 41 years, administered a detailed questionnaire and performed a battery of screening laboratory tests. Young patients were chosen in an effort to exclude the illnesses of older age groups that might confound the results.

Of the 297 patients, 65 (22%) noted unexplained fatigue that has persisted for more than one month, fatigue unexplained by the lack of rest, illness, or undo physical or mental exertion. Fifteen (23%) of these patients met the diagnostic criteria for chronic fatigue syndrome, an illness characterized by prolonged and severe fatigue.

When the 65 patients with unexplained chronic fatigue were compared to the remaining group of 232 patients most sinus symptoms were much more common in the group with unexplained chronic fatigue: facial pressure (80% vs 13%), heavy-headedness (80% vs 8%), nasal obstruction (87% vs 42%), frontal headache (53% vs 6%), sore throat (33% vs 8%) and cervical node tenderness (60% vs 6%.)

Of note, symptoms usually associated with unexplained illnesses such as gastrointestinal problems, sleep disturbance, and psychiatric illness were similar in the group with unexplained chronic fatigue when compared to the group with fatigue explained by a physical or mental illness.  However, sinus symptoms were much more common in the former when compared to the latter.

The results confirmed my suspicion that there is a peculiar and predominant relationship between chronic sinusitis and unexplained fatigue.