Embargoed for Release: May 20, 2003, 12:00 PM EDT
Embargoed for Release: May 20, 2003, 12:00 PM EDT
Results of the largest study of bilateral lung volume reduction surgery (LVRS) to treat severe emphysema indicate that, on average, patients who undergo LVRS with medical therapy are more likely to function better after two years and do not face an increased risk of death compared to those who receive medical therapy only. The National Emphysema Treatment Trial (NETT), a five-year, multicenter, randomized study, evaluated the effectiveness and safety of adding LVRS to medical therapy with pulmonary rehabilitation for patients with advanced emphysema.
The effects of LVRS varied widely among patients, however. Researchers identified two characteristics that helped predict the outcome of the surgery for individual patients: the distribution of emphysema -- that is, whether the damage was concentrated in the upper areas of the lungs -- and the patient's exercise capacity. Patients whose emphysema was predominantly in the upper lobes of the lung and whose exercise capacity was low after pulmonary rehabilitation but prior to surgery were more likely to survive longer and function better after LVRS compared to similar patients who received medical therapy only. In contrast, in patients who did not have upper lobe distribution of emphysema and who had greater exercise capacity, LVRS decreased survival and failed to improve functional levels.
The findings are being presented May 20, 2003, at the American Thoracic Society 99th International Conference in Seattle, Washington. The results are being posted simultaneously on the New England Journal of Medicine (NEJM) Web site (www.nejm.org) and printed in the May 22 print edition of NEJM.
The study began in 1996 as a cooperative effort between the National Heart, Lung, and Blood Institute (NHLBI) -- a component of the National Institutes of Health (NIH) -- and the Centers for Medicare & Medicaid Services (CMS). NHLBI funded and administered the study, and CMS supported participants' care costs; both are agencies of the U.S. Department of Health and Human Services (HHS). In addition, HHS' Agency for Healthcare Research and Quality (AHRQ) contributed support for an analysis of the cost effectiveness of LVRS based on NETT data, which is published separately in the same issue of NEJM.
"NETT was developed in response to concerns that lung volume reduction surgeries were becoming more common despite insufficient knowledge about the procedure's safety and effectiveness," said NHLBI Director Claude Lenfant, M.D. "NETT is a prime example of why clinical trials are needed -- the study results provide vital new information on the benefits and risks of this surgery for patients with different characteristics."
The NETT results will directly impact Medicare coverage policy. "Our agency is reassessing Medicare coverage of the procedure, and we will base our recommendations largely on the results of this important study," commented CMS Chief Medical Officer Sean Tunis, M.D. "This clinical trial reflects a unique collaboration which enabled Medicare beneficiaries to participate in a study of a promising, yet unproven, procedure and contribute to the advancement of science through the nation's premiere medical research agency."
NETT researchers at 17 clinical sites studied survival, exercise ability, lung function, quality of life scores, dyspnea (shortness of breath), and illness and hospitalization rates of 1,218 patients with severe emphysema for an average follow up of 29 months. At the start of the study, all participants received 6 to 10 weeks of pulmonary rehabilitation, which included education, counselling, exercise training, and other techniques to help patients understand and manage their condition, and optimize their ability to perform activities of daily living. The participants were then randomly divided into two groups: 608 patients were selected to receive surgery in addition to medical therapy, and 610 continued receiving medical therapy only.
On average, lung function and exercise capacity among surviving surgical patients improved significantly following LVRS, but after two years returned to about the same levels as before the procedure. In contrast, participants who received only medical therapy on average deteriorated in their functional levels to below baseline. Although the overall mortality rate throughout the follow-up period was similar between the two groups, the risk of death during the first 90 days was significantly higher for patients who underwent surgery compared to those who received medical therapy only (7.9 percent versus 1.3 percent).
"NETT provides the scientific evidence that establishes which patient characteristics are more accurate in predicting the surgical outcome," noted Alfred P. Fishman, M.D., of the University of Pennsylvania, chair of the NETT Steering Committee. "Before NETT, we could only make assumptions based on limited data. Only one characteristic previously believed to be a predictor was proven to be accurate, and we identified a characteristic that had not been considered before."
"Perhaps most importantly, the NETT results identify who is at high risk for surgery," added Fishman. "Some patients who are now known to be at high risk received surgery in the past."
In May 2001, the NETT Data and Safety Monitoring Board (DSMB) identified a subgroup of participants who had a high risk of mortality with little chance of functional benefit from LVRS. These participants had severe airflow obstruction and either limited ability to exchange oxygen when breathing or widespread damage (non-upper lobe emphysema) in the lungs. Based on the DSMB's conclusions and recommendation, NHLBI and the NETT investigators altered the trial's protocol, and shortly thereafter they stopped enrolling patients who were then considered at high risk for the surgery. The final results confirm these early findings, which were published on the NEJM Web site on August 14, 2001, and in the print publication on October 11, 2001.
"Clearly, physicians and patients must weigh the risks of LVRS against the procedure's potential for long-term benefits," added Gail Weinmann, M.D., NHLBI project officer for NETT. "The NETT findings will help patients and their physicians make more informed decisions about whether lung volume reduction surgery is right for them."
NETT investigators also conducted a prospective cost-effectiveness analysis over three years of follow up as part of the trial. They found that in the short term, LVRS added to medical therapy was less cost effective than many surgical procedures, in part because of high costs related to the procedure. For the LVRS group, average costs were very high in the first year following surgery due to expected procedure-related expenses as well as for prolonged postoperative inpatient care, which was needed by a large proportion of the patients. In the third year of follow up, however, total medical care costs were equivalent in both the LVRS and the medical therapy only groups. Nonmedical costs such as transportation for and time in treatment, and time spent by unpaid caregivers (family and friends), were similar overall for both treatment groups.
Whether LVRS will prove cost effective over the long term remains uncertain. To estimate cost effectiveness beyond the trial, NETT investigators applied statistical modeling based on observed trends in survival, cost, and quality-of-life measures. They concluded that if the benefits from LVRS are maintained, the cost effectiveness for surgery added to medical therapy could ultimately approach levels consistent with other treatments that are considered of good value. This outcome would be especially likely for patients found to gain the most from LVRS -- those with upper-lobe emphysema and low exercise capacity - who demonstrated higher survival rates and quality-of-life scores at the end of the three-year period.
Emphysema is a progressive, chronic, and disabling lung condition that affects 2 million Americans, primarily individuals over age 50 who are current or former cigarette smokers. With emphysema, breathing becomes difficult as the fine architecture of the lung is destroyed, leading to large holes in the lung, obstructed airways, trapping of air, and difficulty exchanging oxygen because of reduced elasticity of the lungs. Emphysema costs more than $2.5 billion in annual health care expenses and causes or contributes to 100,000 deaths in the U.S. each year.
Current medical treatments include smoking cessation for those who still smoke, exercise rehabilitation, oxygen therapy for those with low blood oxygen levels, supportive and preventive measures such as flu shots and pneumonia vaccine, medications such as bronchodilators to help open airways, and prompt treatment of respiratory infections. In LVRS, 25 percent to 30 percent of the most damaged regions of each lung is surgically removed. Scientists believe that by surgically removing functionally useless tissue, air will move in and out of the remaining lung more readily, thereby easing symptoms associated with advanced emphysema and improving overall lung function.
To arrange an interview with Dr. Gail Weinmann, NHLBI project officer for NETT, please call the NHLBI Communications Office at (301) 496-4236.
NHLBI press releases, resources for professionals and consumers, and other materials are online at www.nhlbi.nih.gov. For more information about NETT, please visit the NETT Study Web Site at http://www.nhlbi.nih.gov/health/prof/lung/nett/lvrsweb.htm.
B-roll with soundbites is available by satellite at AMC2, Transponder 23, DL 4160, C-Band on Tuesday, May 20, 10:30 am to 10:45 am, and at AMC2, Transponder 11, DL 3920, C-Band on Tuesday, May 20, 1:00 pm to 1:15 pm and Wednesday, May 21, 1:15 pm to 1:30 pm. (All times are EST.)