Sildenafil-statin combo found to boost exercise capacity in COPD-PH
Trial review says treatment's use could lead to better patient outcomes
Treatment with a combination of sildenafil and statins improved exercise capacity and reduced pulmonary arterial pressure in people with pulmonary hypertension (PH) secondary to chronic obstructive pulmonary disease (COPD) — a condition known for short as COPD-PH — according to a review study by scientists in China.
These findings, culled from a dozen trials conducted in the Asian nation, also showed that the use of this therapy combo improved patients’ lung function, and posed no significant safety concerns, the team noted.
“Currently, there are no standardized targeted treatment protocols specifically designed for COPD-PH,” the researchers wrote.
According to the team, “these findings support the integration of sildenafil-statin combination therapy into the clinical management of COPD-PH, offering a promising approach to improving patient outcomes.”
Their study, “Efficacy of sildenafil combined with statins in treating pulmonary hypertension secondary to chronic obstructive pulmonary disease,” was published in the journal Pathology – Research and Practice.
Sildenafil (sold as Revatio, with generic medications available) is approved to treat pulmonary arterial hypertension, a rare type of PH. Statins are a type of medication used to help reduce cholesterol levels in the blood.
PH is characterized by high blood pressure in the blood vessels, known as the pulmonary arteries, that supply the lungs. Disease processes in PH include vascular remodeling, or structural alterations to blood vessels, and inflammation.
The chronic condition may be caused by COPD, a persistent inflammatory disease of the lungs that limits airflow and results in significant respiratory symptoms like shortness of breath.
Oxygen therapy for COPD-PH fails to normalize pulmonary arterial pressure
Current guidelines recommend treating COPD-PH with long-term oxygen therapy, but research has shown that this approach — while helping to reduce PH severity — fails to normalize pulmonary arterial pressure.
Statins, conversely, have been deemed likely to be beneficial in the management of PH due to their effects against cell growth, and by inhibiting the formation of blood clots. Moreover, statins have anti-inflammatory and antioxidant properties, while also promoting the health of cells lining blood vessels.
Guidelines currently lack robust evidence for the targeted management of COPD-PH, according to the scientists. Studies have shown benefits of using statins or sildenafil as standalone therapies for COPD-PH, but none have comprehensively evaluated their use in combination, the team noted.
In this study, the scientists conducted a systematic review of 12 trials conducted in China between 2010 and 2020. The team assessed the use of sildenafil with statins for managing PH secondary to COPD.
“We also reviewed relevant literature to evaluate whether this drug combination can achieve a more effective therapeutic outcome” than either treatment alone, the team noted.
Data came from 937 patients who received either a sildenafil/statin combination or a placebo (or standard therapy) for three to six months. Assessments of exercise capacity and pulmonary arterial blood pressure were the main goals, with markers of lung function and inflammation evaluated as secondary outcome measures.
Researchers cite ‘urgent need’ for larger, more widespread trials
The key measure of exercise capacity used was the 6-minute walk distance (6MWD) test, which, as its name suggests, assesses the distance, in meters, walked by patients over a six-minute period. Pooled study results demonstrated that the sildenafil/statin combination significantly increased 6MWD results by a mean of 49.7 meters (163 feet), compared with control groups (placebo, statins alone, or sildenafil alone).
“This indicates that while statins or sildenafil alone can also extend 6MWD to some extent, the combination of statins and sildenafil yields more significant results, further improving patients’ exercise tolerance and quality of life,” the investigators wrote.
The treatment combination also significantly reduced pulmonary arterial pressure by a mean of 4.31 mmHg and improved lung function, measured by the FEV1/FVC ratio, by 4.08%. FEV1 stands for forced expiratory volume in one second and is the maximum volume of air one can forcefully exhale in the first second. FVC means the total amount of air exhaled after a deep breath.
These findings suggest a synergistic interaction between sildenafil and statins, highlighting the potential superiority of combined therapy over individual treatments.
Patients also experienced a clinically meaningful improvement of 3.82 mmHg in arterial oxygen tension, a measure of the amount of oxygen in the blood, and a mean reduction of 6.1 mg/L in the levels of high-sensitivity C-reactive protein, a marker of inflammation.
Seven of the 12 trials evaluated safety. The most commonly reported adverse events were headaches, abdominal pain, flushing, dizziness, and elevated levels of liver enzymes, and were similar between the combination therapy and control groups.
“These findings suggest a synergistic interaction between sildenafil and statins, highlighting the potential superiority of combined therapy over individual treatments,” the researchers wrote.
Still, the team said further research is necessary, given the retrospective nature of this review.
“There is an urgent need for large-scale, high-quality, multicenter randomized controlled trials to provide more robust evidence and further validate the clinical application of this therapeutic approach.”
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