Since there is no known cure for idiopathic pulmonary fibrosis (IPF), medical experts continually seek other potential alternatives. In a new study,1 doctors put two medications—angiotensin-converting enzyme (ACE) inhibitors and statins—to the test.
New Effect for Two Common Drugs?
ACE inhibitors and statins are well-known drugs on the front lines against heart disease. ACE inhibitors work by blocking the actions of angiotensin, a substance that causes blood vessels to narrow.2 Similarly, statins are a class of medications used to lower cholesterol in the blood, a well-known risk factor for the development of cardiovascular disease.3
But researchers have found that both of these drugs can also help reduce fibrosis, based on preclinical studies both on animals and in lab tests.4,5 It's also been suggested that angiotensin plays a role in the development of fibrosis in the lung. Armed with that information, doctors at the Mayo Clinic reviewed the records of 82 patients with IPF at their institution who had received ACE inhibitors and/or statins as part of their treatment for the disease.
IPF is a disease characterized by scarring of the lung. Gradually, the lungs' air sacs become replaced by fibrous tissue, and when this scarring forms, the tissue gets thicker, causing an irreversible loss of its ability to transfer oxygen into the bloodstream. Symptoms include shortness-of-breath, chronic cough, fatigue and weakness, chest discomfort, loss of appetite, and rapid weight loss. Currently, there is no cure for idiopathic pulmonary fibrosis, nor are its causes known.6
Pulmonary hypertension can occur secondarily to IPF; that is, it can occur after someone has been diagnosed with lung fibrosis.7
"No [medication] has been rigorously shown to improve survival or quality of life for patients with IPF," wrote the Mayo research team. "Consequently, IPF generally progresses relentlessly and carries the poorest prognosis of the chronic idiopathic interstitial pneumonias, with a median survival of less than three years."
Do These Drugs Improve Survival Odds?
After determining which patients during the study period had received statins and/or ACE inhibitors for idiopathic pulmonary fibrosis, the investigators then determined each individual's odds of survival from the disease. When comparing notes, they found no differences in survival odds for those taking ACE inhibitors alone or not at all. "For those subjects receiving ACE inhibitors, the median [rate of] survival was 2.2 years versus 2.9 years in subjects not prescribed ACE inhibitors," the study authors wrote. Still, this finding was determined not to be statistically significant, meaning it could have arisen due to chance alone, and can't necessarily be applied to the general population of people with IPF (95% confidence interval, 0.96 to 1.85; p=0.08).
When the investigators compared the odds of survival for patients receiving either ACE inhibitors and/or statins to those not receiving either medicine individually or in combination, again, no differences were found. The average survival for those who had been given ACE inhibitors and/or statins combined was about 2-and-a-half years, compared to 3 years for those not prescribed either drug, they wrote. But this finding was also not significant (95% confidence interval, 0.98 to 1.73; p=0.06).
Researchers Still Hold Out Hope
Because of the insignificant findings, and other limits to this study, including the fact that patients were not prospectively assigned at random to receive either drug and compared with patients taking a placebo as what occurs in controlled randomized clinical trials, the investigators still hold out hope that ACE inhibitors and statins may have some benefit to people with IPF.
Another drawback to the study is the fact that the investigators did not take into account varying drug doses and types prescribed, varying types of therapies taken simultaneously by the patients, and information on the duration of the drugs taken before IPF diagnosis was made, they pointed out.
"In conclusion, we were not able to demonstrate survival differences between the groups receiving ACE inhibitors and/or statins versus neither," the Mayo researchers wrote. "We conclude that ACE inhibitors and/or statins are not associated with improved survival in IPF, but acknowledge that the limitations of the data set to not definitely preclude an eventual beneficial role for these agents in this enigmatic disorder."
1. Nadrous HF, Ryu JH, Douglas WW, Decker PA, Olson EJ. Impact of angiotensin-converting enzyme inhibitors and statins on survival in idiopathic pulmonary fibrosis. Chest 2004 Aug;126(2):438-46.
2. American Heart Association. ACE inhibitor drugs underused in heart failure patients. Available at: http://www.americanheart.org/presenter.jhtml?identifier=3023710. Accessed October 28, 2004.
3. Mayo Foundation for Medical Education and Research. Statin Drugs: Potential Side Effects. Available at: http://www.mayoclinic.com/invoke.cfm?id=AN00587. Accessed October 28, 2004.
4. Nie L, Imamura M, Itoh H, Ueno H. Pitavastatin enhances the anti-fibrogenesis effects of candesartan, an angiotensin II receptor blocker, on CC14-induced liver fibrosis in rats. J UOEH 2004 Jun 1;26(2):165-77.
5. Gross O, Schulze-Lohoff E, Koepke ML et al. Antifibrotic, nephroprotective potential of ACE inhibitor vs AT1 antagonist in a murine model of renal fibrosis. Nephrol Dial Transplant 2004 Jul;19(7):1716-23. Epub 2004 May 5.
6. Pulmonary Fibrosis Foundation. What is Pulmonary Fibrosis?
7. Olschewski H, Ghofrani HA, Walmrath D et al. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med 1999 Aug;160(2):600-7.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
