On Nov. 14, 1997, the U.S. Department of Health and Human Services released a report regarding cardiac valvulopathy associated with the use of appetite suppressants containing fenfluramine or dexfenfluramine (with or without phentermine) ("Morbidity and Mortality Weekly Report," the Centers for Disease Control and Prevention, 1997;46:1061–66).
In that report, several "interim" recommendations were published that were immediately echoed by the ADA and the American Heart Association through statements issued concurrently with recommendations from the Centers for Disease Control and Prevention.
In those statements, all three organizations essentially stated or implied:
- – any patient that had taken fenphen or dexfenfluramine for any length of time was at risk for potential cardiac damage;
- – patients who required emergency invasive dental procedures should be empirically covered with prophylactic antibiotic therapy until they can undergo cardiac evaluation;
- – patients should be referred for medical evaluation before any elective, invasive dental treatment is started.
To the best of my knowledge, these "interim" guidelines have not been revised since their hasty issuance in late 1997, and it is probably safe to say that multiple thousands of dental patients are presently receiving dental care with these recommendations in place; that is, dental treatment provided under empiric antibiotic coverage, with the associated increased costs and therapeutic risks of such coverage.
Since the original report by the CDC, a number of studies have been published that have examined the effects of these two appetite suppressants on the heart. Although an occasional study has supported the opinion that short-term regimens (that is, less than three to four months) of fenfluramine or dexfenfluramine can cause valvular damage in a significant number of patients (
Khan MA and colleagues, "The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs," New Eng J Med 1998;399:713–18
), the majority of reports have not (
Burger AJ and colleagues, "Low prevalence of valvular heart disease in 226 phenterminefen-fluramine protocol subjects prospectively followed for up to 30 months," JACC 1999; 34:1153–58[Abstract/Free Full Text]
;
Jick H and colleagues, "A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation," N Eng J Med 1998;339:719–24[Abstract/Free Full Text]
;
Weissman NJ and colleagues, "An assessment of heart-valve abnormalities in obese patients taking defenfluramine, sustained-release dexfenfluramine, or placebo," New Eng J Med 1998;339:725–32[Abstract/Free Full Text]
).
In Jick et al.’s study, the risk was significant in patients on long-term dosages, but was calculated to be .071 percent for patients who took the drugs for three months or less. In Weissman et al.’s article, the authors state, "The difference . . . was small . . . for patients who have taken dexfenfluramine for two to three months."
In fact, some authors have been very critical of the original research, the U.S. Food and Drug Administration criteria and of subsequent studies that supported the premise of these drugs causing damage to the heart with short-term usage (Schiller NB, "Fen/phen and valvular heart disease: If it sounds too bad to be true, perhaps it isn’t," JACC 1999; 34: 1159–62).
One author states, "The incidence of clinically overt valvular disease after the use of appetite suppressants for three or fewer months . . . was low after four years of follow-up (less than 1 case per 1,000 patient years) . . . clinically important valvular disease will probably not develop in most patients with short-term exposure ... " (Devereux RB, "Appetite suppressants and valvular heart disease," New Eng J Med 1998; 399:765–66). The author does note, however, that further studies are necessary to clarify the need for evaluations. In a recent editorial in the Journal of the American College of Cardiology, Schiller criticizes the study designs and methodology of the pro-damage studies and suggests that echocardiography is being incorrectly applied as a diagnostic tool for evaluating these cases.
All in all, most of the credible research that I have read recently strongly suggests that the risk of cardiac damage in patients who took appetite suppressants for less than four months is extremely low, if present at all. Since patients who have taken one of the drugs for only a few weeks or months compose a sizable portion of the patients I see in my practice, this therefore creates a clinical probability that significant numbers of these patients (supposedly up to 4.6 million patients) on empiric prophylactic antibiotic regimens prior to invasive dental procedures are being exposed to unnecessary additional expenses for dental care and medical evaluations—and to the possibility of life-endangering allergic reactions.
I also can’t help but wonder if all of this excessive antibiotic usage is contributing to the growing problem of antibiotic resistance in this country.
Published recommendations that patients who have taken these drugs for any length of time seek expensive medical workup prior to dental treatment to rule out the need for antibiotics (or automatically receive antibiotics) fail to recognize that significant numbers of patients do not have medical insurance for such evaluations and do not even have regular physicians.
For these patients, almost every dental appointment becomes an appointment where "empiric" coverage becomes necessary under existing guidelines.
Where are the ADA, the AHA and the FDA in this process? Why isn’t the FDA being pressured to publish scientifically rational modifications to the original "interim" guidelines (now two years old)?
By my interpretation of the medical literature, a growing body of articles suggest that patients who took these appetite suppressants for three months or less and who have no clinical cardiac symptoms are at extremely low risk and presumably do not require empiric antibiotic prophylaxis.
Most dental practitioners, however, are reluctant to incur the legal risks of acting contrary to published national guidelines. I believe it would be comforting to many dental clinicians if they could see a comprehensive review and revised guidelines forthcoming from the FDA and/or the ADA Council on Scientific Affairs on this matter.
In my opinion, such an updated statement is long overdue and will contribute to reducing the inappropriate routine use of antibiotics in dental practice for what appears to be a very minor risk.
