Richard N Channick, Gérald Simonneau, Olivier Sitbon, Ivan M Robbins, Adaani Frost, Victor F Tapson, David B Badesch, Sébastien Roux, Maurizio Rainisio, Frédéric Bodin, Lewis J Rubin

Division of Pulmonary and Critical Care Medicine, University of California San Diego, CA, USA (R N Channick MD, Prof L J Rubin MD); University of Colorado Health Sciences Center, Denver, CO (Prof D B Badesch MD); Baylor College of Medicine and the Methodist Hospital, Houston, TX (Prof A Frost MD); Vanderbilt University School of Medicine, Nashville, TN (I M Robbins MD); Hôpital Antoine Béclère, Clamart, France (Prof G Simonneau MD, O Sitbon MD); Duke University Medical Center, Durham, NC (V F Tapson MD); Actelion Ltd, Allschwil, Switzerland (S Roux MD, F Bodin MD); and Statistics for Research Ltd, Basel, Switzerland (M Rainisio PhD).

Lancet 2001; 358: 1119-23

Background Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension. We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in patients with severe pulmonary hypertension.

ethods In this double-blind, placebo-controlled study, 32 patients with pulmonary hypertension (primary or associated with scleroderma) were randomly assigned to bosentan (62·5 mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. The primary endpoint was change in exercise capacity. Secondary endpoints included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO functional class, and withdrawal due to clinical worsening. Analysis was by intention to treat.

indings In patients given bosentan, the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by 6 m in those on placebo (difference 76 m [95% CI 12-139], p=0·021). The improvement was maintained for at least 20 weeks. The cardiac index was 1·0 L min^-1 m^-2 (95% CI 0·6-1·4, p<0·0001) greater in patients given bosentan than in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm^-5 with bosentan, but increased by 191 dyn s cm^-5 with placebo (difference -415 [-608 to -221], p=0·0002). Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class. All three withdrawals from clinical worsening were in the placebo group (p=0·033). The number and nature of adverse events did not differ between the two groups.

Interpretation Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.

 

VA Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, VT 05009, USA (L M Schwartz MD, S Woloshin MD, H G Welch MD); Center for the Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, NH (L M Schwartz, S Woloshin, H G Welch); Norris Cotton Cancer Center, Lebanon, NH (L M Schwartz, S Woloshin); and Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH (J Tremmel MD)

Lancet 2001; 358: 1141-46

Correspondence to: Dr L M Schwartz (e-mail:lisa.schwartz@dartmouth.edu)

 

Background Pharmaceutical companies spent US$1·8 billion on direct-to-consumer advertisements for prescription drugs in 1999. Our aim was to establish what messages are being communicated to the public by these advertisements.

Methods We investigated the content of advertisements, which appeared in ten magazines in the USA. We examined seven issues of each of these published between July, 1998, and July, 1999.

Findings 67 advertisements appeared a total of 211 times during our study. Of these, 133 (63%) were for drugs to ameliorate symptoms, 54 (26%) to treat disease, and 23 (11%) to prevent illness. In the 67 unique advertisements, promotional techniques used included emotional appeals (45, 67%) and encouragement of consumers to consider medical causes for their experiences (26, 39%). More advertisements described the benefit of medication with vague, qualitative terms (58, 87%), than with data (9, 13%). However, half the advertisements used data to describe side-effects, typically with lists of side-effects that generally occurred infrequently. None mentioned cost.

Interpretation Provision of complete information about the benefit of prescription drugs in advertisements would serve the interests of physicians and the public.