by Phyllis Hanlon, Contributing Writer
All of the 14 targeted therapies for pulmonary hypertension (PH) are approved for use in patients with World Health Organization (WHO) Group 1 PH (pulmonary arterial hypertension, or PAH), with one therapy also approved for use in patients with inoperable or recurrent WHO Group 4 PH (chronic thromboembolic pulmonary hypertension, or CTEPH).
Most patients have other forms of PH, including PH due to left heart disease and PH due to chronic lung disease, which are not treated through a PH-specific therapy, but rather by treating the underlying heart or lung disease.
There have been few studies about the treatment of PH for people who have WHO Group 3 PH, PH that is associated with other lung diseases such as chronic obstructive pulmonary disease (COPD). A team of physicians and researchers from Italy conducted a study to determine what effects sildenafil, a phosphodiesterase 5 inhibitor, might have on blood flow in the pulmonary arteries and gas exchange in the lungs of patients with severe PH that is associated with COPD. Carmine Dario Vizza, M.D., Department of Cardiovascular and Respiratory Science at the Sapienza University of Rome, and Patrizio Vitulo, M.D., Pulmonology Unit of the IRCCS ISMETT Palermo, led a team of experts in conducting the study at seven centers experienced in managing people with PH and COPD.
In this study, the researchers worked with 28 patients with severe PH with COPD. Eighteen patients received sildenafil and 10 patients were given a placebo (sugar pill). The researchers analyzed whether patients taking sildenafil had a decrease in pulmonary vascular resistance (PVR) compared to participants taking a placebo. Researchers also evaluated differences in the BODE index (body mass, airflow obstruction, dyspnea [shortness of breath] and exercise capacity), the six-minute walk test (6MWT) and results from a quality-of-life questionnaire.
At the end of the 16-week study, the authors found that patients in the sildenafil group had reduced PVR and their BODE index had improved. Sildenafil also enhanced the patients’ quality of life and, most importantly, did not have a harmful effect on gas exchange, a process in which oxygen goes from the lungs into the bloodstream and eliminates carbon dioxide (a waste product) from the bloodstream to the lungs.
Although the results were promising, the authors pointed out a few limitations to this study. The number of patients participating in the study was small – only 28 participants – but they noted that this was the largest study of its kind on the effects of sildenafil in patients with PH and COPD. Also, the study used a specific dose of sildenafil, so researchers were unable to test whether patients did better or worse on a lower or higher dose. Finally, this study did not provide statistics on mortality rates or the time it took for the patients’ conditions to worsen; the short observation time did not allow for such reporting, according to the authors.
The authors indicated that the few other trials that have examined the effect of PH-targeted drugs on patients with PH and COPD have produced inconclusive results, which they attributed largely to study design. In contrast, this study showed that treatment with sildenafil in people with PH and COPD was safe and effective. The authors recommended that future trials include the BODE index rather than the 6MWT to help assess the effectiveness of PH-targeted drugs in patients with PH and COPD.