LANDMARK COOPERATIVE FEDERAL STUDY DEFINES THE ROLE
OF LUNG SURGERY IN THE TREATMENT OF SEVERE EMPHYSEMA
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 – 10:45 am,
and at AMC2, Transponder 11, DL 3920, C-Band on Tuesday, May 20,
1:00 pm – 1:15 pm and Wednesday, May 21, 1:15 pm – 1:30
pm. (All times are Eastern Time.)
NHLBI is part of the National Institutes of Health (NIH),
the Federal Government's primary agency for biomedical and behavioral
research. NIH is a component of the U.S. Department of Health and
Human Services. NHLBI press releases and other materials including
information about high blood pressure, high blood cholesterol, and
heart disease, are available online at www.nhlbi.nih.gov.
|