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Communications to the Editor |

The Age-Adjusted Mortality Rate From Primary Pulmonary Hypertension, in Age Range 20 to 54 Years, Did Not Increase During the Years of Peak “Phen/Fen” Use FREE TO VIEW

Richard B. Rothman, MD, PhD
Author and Funding Information

Fairfax, VA

Correspondence to: Richard B. Rothman, MD, PhD, 10505 Judicial Drive, Suite 201, Fairfax, VA 22030; e-mail: rrothman@belite.com



Chest. 2000;118(5):1516-1517. doi:10.1378/chest.118.5.1516
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To the Editor:

Lilienfeld and Rubin (March 2000)1 recently estimated the mortality rates from primary pulmonary hypertension (PPH) in the United States during the years 1979 through 1996 using the mortality database maintained by the Centers for Disease Control and Prevention (CDC; http://wonder.cdc.gov). Their major finding was increased mortality rates from PPH since 1979, especially among infants and elderly black women. I address two issues in this letter.

First, the mortality rate for white men was 0 from 1979 to 1981, 0 in 1983, and again in 1991. Similarly, the rate for white women was 0 from 1979 to 1983. With an incidence of one to two cases of PPH per million per year,2 the CDC database may be seriously underestimating PPH mortality in the early 1980s. Given the uncertainty in the baseline rate of PPH mortality, it is difficult to see how one can determine if the PPH mortality observed in subsequent years was significantly increased, decreased, or remained unchanged.

Second, despite the fact that the death certificates did not provide information on patients’ use of appetite suppressants, and despite the fact that the group of patients with the highest mortality (infantsand elderly black women) were the least likely to be exposed to these medications, the authors concluded in their abstract that “some portion of this increase [in PPH mortality] may be related to the introduction of anorexigens.”1

To test this hypothesis somewhat differently, I queried the CDC mortality database for PPH deaths, using an age range more typical of patients who enroll in weight loss programs. To determine the age range of patients who typically enroll in weight loss programs that utilize appetite suppressant medications, this writer ascertained the ages of 7,329 patients who had enrolled in weight loss programs in the Washington, DC, metropolitan area. The median age of patients was 39.8 years. The age range of 20 to 54 years comprised 91.3% of the total patient population and was used for the query. Data from the years 1991 to 1992 were used to provide an estimate of the PPH mortality rate prior to use of phentermine/fenfluramine (phen/fen). After the publication of the Weintraub studies3 in 1992, the use of phen/fen rapidly increased until fenfluramine was withdrawn from the marketplace in 1997. Thus, the years from 1992 to 1997 were used as the comparison period when the population was exposed to phen/fen.

The results (Table 1 ) show that the age-adjusted PPH mortality rates in the years immediately preceding the use of phen/fen are not different from those reported during the years of widespread phen/fen use for patients aged 20 to 54 years.

This analysis fails to support the hypothesis that the widespread use of phen/fen in the years from 1992 to 1997 increased the incidence of PPH. If the use of phen/fen during these years created an“ epidemic” of PPH, as some have declared,2,4such an epidemic is not yet reflected in the mortality database maintained by the CDC. Continued surveillance, such as the Surveillance of North American Pulmonary Hypertension study,5 is warranted to assess the relationship between exposure to fenfluramine derivatives and PPH.

Table Graphic Jump Location
Table 1. Age-Adjusted Mortality Rate from PPH in the Age Range 20–54 Years (Cases/Million)*
* 

The comparison year for age adjustment was 1990.

References

Lilienfeld, DE, Rubin, LJ (2000) Mortality from primary pulmonary hypertension in the United States, 1979–1996.Chest117,796-800. [CrossRef] [PubMed]
 
Abenhaim, L, Moride, Y, Brenot, F, et al Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group (comment).N Engl J Med1996;335,609-616. [CrossRef] [PubMed]
 
Weintraub, M Long-term weight control study: conclusions.Clin Pharmacol Ther1992;51,642-646. [CrossRef] [PubMed]
 
Simonneau, G, Fartoukh, M, Sitbon, O, et al Primary pulmonary hypertension associated with the use of fenfluramine derivatives.Chest1998;114(suppl),195S-199S
 
Rich, S, Rubin, L, Walker, AM, et al Anorexigens and pulmonary hypertension in the United States: results from the Surveillance of North American Pulmonary Hypertension.Chest2000;117,870-874. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Age-Adjusted Mortality Rate from PPH in the Age Range 20–54 Years (Cases/Million)*
* 

The comparison year for age adjustment was 1990.

References

Lilienfeld, DE, Rubin, LJ (2000) Mortality from primary pulmonary hypertension in the United States, 1979–1996.Chest117,796-800. [CrossRef] [PubMed]
 
Abenhaim, L, Moride, Y, Brenot, F, et al Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group (comment).N Engl J Med1996;335,609-616. [CrossRef] [PubMed]
 
Weintraub, M Long-term weight control study: conclusions.Clin Pharmacol Ther1992;51,642-646. [CrossRef] [PubMed]
 
Simonneau, G, Fartoukh, M, Sitbon, O, et al Primary pulmonary hypertension associated with the use of fenfluramine derivatives.Chest1998;114(suppl),195S-199S
 
Rich, S, Rubin, L, Walker, AM, et al Anorexigens and pulmonary hypertension in the United States: results from the Surveillance of North American Pulmonary Hypertension.Chest2000;117,870-874. [CrossRef] [PubMed]
 
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