Correspondence

Aerosolized Iloprost for Primary Pulmonary Hypertension

N Engl J Med 2000; 343:1421-1422November 9, 2000

Article

To the Editor:

Hoeper et al. (June 22 issue)1 reported improved hemodynamics in a group of 24 patients with primary pulmonary hypertension who were treated with aerosolized iloprost for at least one year. In contrast, we studied 18 such patients who were treated with inhaled iloprost for 12 months and found that the 15 patients with hemodynamic follow-up data had no significant changes from base-line values in preinhalation hemodynamics (pulmonary-artery pressure, 61±16 mm Hg; carbon monoxide, 3.0± 2.1 liters per minute; and pulmonary vascular resistance, 1736±656 dynseccm^–5).2 Right atrial pressure even increased from 5.4±4.2 to 8.5±6.1 mm Hg (P<0.05). Both studies used the same inhalation devices and dose ranges. Hemodynamically, our patients were more severely compromised at base line, indicating that they had more advanced disease than did the patients in the study by Hoeper et al. (mixed venous oxygen saturation, 57±8 percent vs. 62±8 percent). However, our patients still derived a clinically significant benefit from inhaled iloprost with respect to functional capacity.3

As is evident from Figure 2 of the article by Hoeper et al., the condition of five patients deteriorated over time, with increasing pulmonary vascular resistance. In another seven patients, pulmonary vascular resistance remained unchanged or was reduced by less than 20 percent. In contrast, the remaining 12 patients had an impressive response at 12 months, with reductions in pulmonary vascular resistance of up to 80 percent. Therefore, we speculate that the 12 patients with minor changes in pulmonary vascular resistance had a lower mixed venous oxygen saturation and are more similar to our patients, whereas the 12 patients with long-term responses probably had less severe disease. Inhaled iloprost may not be the optimal treatment for the entire spectrum of patients with primary pulmonary hypertension, as suggested by a recent report.4

Ralph Ewert, M.D.
Roland Wensel, M.D.
Christian F. Opitz, M.D.
Deutsches Herzzentrum Berlin, 13353 Berlin, Germany

4 References

1. 1

   Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000;342:1866-1870
   Full Text | Web of Science | Medline

2. 2

   Opitz CF, Wensel R, Ewert R, Bruch L, Kleber FX. Preserved long-term efficacy of iloprost inhalation therapy over 2 years in patients with primary pulmonary hypertension. J Am Coll Cardiol 2000;35:Suppl A:286A-286A abstract.
   Web of Science

3. 3

   Wensel R, Opitz CF, Ewert R, Bruch L, Kleber FX. Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Circulation 2000;101:2388-2392
   Web of Science | Medline

4. 4

   Olschewski H, Ghofrani HA, Schmehl T, et al. Inhaled iloprost to treat severe pulmonary hypertension: an uncontrolled trial. Ann Intern Med 2000;132:435-443
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Ewert and coworkers suggest that inhaled iloprost may not be the optimal treatment for every patient with primary pulmonary hypertension. We fully agree with this statement. However, as we noted in our article, the individual response to inhaled iloprost is not predictable. In our population of patients, there was no significant difference in base-line hemodynamic variables, mixed venous oxygen saturation, or exercise capacity between patients who had a favorable long-term response to aerosolized iloprost and those who did not. Furthermore, in a recent German study, inhaled iloprost had beneficial effects in a substantial group of patients with very severe pulmonary hypertension.1 Therefore, it may not be appropriate to conclude at this time that inhaled iloprost may be the preferable treatment for patients with less severe forms of pulmonary hypertension. However, patients who are receiving aerosolized iloprost should be monitored closely, and in the event of a deterioration in their condition, the initiation of long-term treatment with intravenous epoprostenol should be seriously considered.

Marius M. Hoeper, M.D.
Edda Spiekerkoetter, M.D.
Helmut Fabel, M.D.
Medizinische Hochschule Hannover, D-30625 Hannover, Germany

1 References

1. 1

   Olschewski H, Ghofrani HA, Schmehl T, et al. Inhaled iloprost to treat severe pulmonary hypertension: an uncontrolled trial. Ann Intern Med 2000;132:435-443
   Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   Ralf Ewert, Sven Gläser, Tom Bollmann, Christoph Schäper. (2011) Inhaled iloprost for therapy in pulmonary arterial hypertension. Expert Review of Respiratory Medicine 5:2, 145-152
   CrossRef

2. 2

   Ralf Ewert, Sven Gläser, Christian Opitz. (2008) Iloprost in pulmonary hypertension. Expert Review of Respiratory Medicine 2:6, 689-702
   CrossRef

3. 3

   David R Goldsmith, Antona J Wagstaff. (2004) Inhaled Iloprost. Drugs 64:7, 763-773
   CrossRef

4. 4

   Thorsten Kramm, Balthasar Eberle, Frank Krummenauer, Stefan Guth, Hellmut Oelert, Eckhard Mayer. (2003) Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy. The Annals of Thoracic Surgery 76:3, 711-718
   CrossRef