Chest
Volume 112, Issue 3, September 1997, Pages 714-721
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Clinical Investigations: Pulmonary Vasculature
The Effect of Anticoagulant Therapy in Primary and Anorectic Drug-Induced Pulmonary Hypertension

https://doi.org/10.1378/chest.112.3.714Get rights and content

In a retrospective study, we tested the hypothesis that anticoagulant therapy with warfarin sodium (Coumadin) has a beneficial influence on the long-term prognosis in patients with primary pulmonary hypertension (PPH) and aminorex-induced plexogenic pulmonary hypertension. The study included a total of 173 patients from two European cities. One hundred four of these patients took the anorectic drug aminorex (Menocil), which was available in some European countries almost 30 years ago; 69 patients had pulmonary hypertension of unexplained etiology, ie, PPH. Fifty-six of the 104 aminorex-treated patients and 24 patients in the PPH group received warfarin after diagnosis was established. For analysis, patients were divided into four groups according to their history of aminorex intake and anticoagulant therapy. Survival time, changes in hemodynamics (pulmonary arterial pressure), and improvement in quality of life (scored by the New York Heart Association [NYHA] classification) were compared and analyzed. We found that aminorex-treated patients had a better long-term prognosis than those with PPH (7.5 vs 3.9 years; p≤0.001). The best mean survival time of 8.3 years was found in anticoagulated aminorex-treated patients, compared to 6.1 years in nonanticoagulated aminorex-treated patients. Moreover, aminorex-treated patients who received anticoagulant therapy soon after the onset of symptoms showed significantly better prognosis (10.9 years) than those who commenced treatment 2 years thereafter (5.9 years) (p≤0.05). In patients with PPH, systolic pulmonary pressure was shown to influence survival time significantly (p≤0.0005); however, this correlation was not found in aminorex-treated patients. An improvement of symptoms like dyspnea on exertion was seen in 44.8% of the anticoagulated aminorex-treated patients, while deterioration was evident in 72.2% of the nonanticoagulated aminorex-treated patients. In conclusion, our study has shown that anticoagulant therapy had a positive influence on long-term survival and a significant improvement in quality of life in patients with PPH, in particular in patients with a history of anorectic drug intake.

Section snippets

Patients

One hundred seventy-three patients (29 men, 144 women) with primary or drug-induced pulmonary hypertension from the Vienna and Berne cardiac centers were studied retrospectively with regard to survival time, changes in pulmonary artery pressure, and quality of life as scored by the New York Heart Association (NYHA) classification. Secondary causes, such as pulmonary embolism, obstructive and restrictive lung disease, intracardial and extracardial shunt lesions, and cardiomyopathies were

Survival Time

General Remarks: We observed that patients with exogenous pulmonary hypertension, such as aminorex-induced plexogenic pulmonary arteriopathy, had a significant better survival time than patients with idiopathic or PPH, independent of any anticoagulant therapy (7.5±0.6 years vs 3.9±0.5 years; p≤0.001). For the entire patient population studied, regardless of whether pulmonary hypertension was exogenous or not, anticoagulation generally showed a significant influence in survival time (7.2±0.6

Discussion

Pulmonary hypertension is usually secondary to cardiac or pulmonary disease and only rarely is “primary, idiopathic” or “unexplained.”7 Aminorex fumarate, which became available as an anorectic drug in three European countries (Germany, Switzerland, Austria), caused an increase in the number of cases of unexplained pulmonary arterial hypertension between 1965 and 1969, also called plexogenic pulmonary arteriopathy.8

Treatment of primary or unexplained pulmonary hypertension remains among the

Acknowledgment

The authors thank Valentin Fuster, MD, and Charles Hales, MD, for their helpful review of this manuscript. We also thank Jo Anne Fordham for proofreading the manuscript and Michael Hiegetsberger, PhD, who produced the graphs for this article.

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