Obesity is a national epidemic associated with increased morbidity and mortality. Bariatric surgery is an alternative to behavioral and medical therapy for weight loss with good long term success at weight loss, and low morbidity and mortality in patients with severe obesity and failed attempts at medical therapy. Observational studies have shown improvements in left ventricular hypertrophy, diastolic and systolic dysfunction and frank heart failure after bariatric surgery. Similar improvements have been seen in dyslipidemia, type 2 diabetes, and obstructive sleep apnea. The use of this procedure is increasing at a rapid rate. Between 1996 and 2008, the number of bariatric surgeries performed in the United States increased thirteen-fold. While NHLBI has a relatively large portfolio of obesity treatment studies, the number focusing on bariatric surgery is small. Few randomized controlled trials testing bariatric surgery have been conducted and those that have been completed have focused primarily on intermediate outcomes such as weight loss.
To help guide future research effort in the area of bariatric surgery and to determine if the state of the science in this field indicates that larger clinical trials should be conducted, National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in Bethesda on January 11 and 12, 2011. Experts in the fields of bariatric surgery, cardiovascular disease, sleep disordered breathing, clinical trials, guideline development, and insurance coverage met for two days to discuss conditions and strategies needed for the conduct of future clinical trials. The members were charged with determining if the state of the science regarding bariatric surgery indicated that a next step is a clinical trial of efficacy in improving outcomes important to NHLBI, including what the most appropriate outcome(s) for such a clinical study might be, and to explore potential study designs.
Over the course of the workshop, participants reviewed and discussed the rationale for future trials of bariatric surgery. The members considered specific populations, intervention and control conditions, and clinical outcomes for inclusion in future clinical trials. Additionally, feasibility issues for conducting clinical trials of surgical interventions were reviewed.
Workshop participants concurred with the need for randomized controlled trials as an important next step in developing a strong evidence base for bariatric surgery. To maximize the potential knowledge gain, an observational arm was considered an essential portion of any future clinical trial. This observational arm would enroll those patients who initially express interest in the trial but ultimately had a strong preference for either surgery or medical therapy. Use of this type of patient preference study design was felt to provide an efficient method of advancing the science of bariatric surgery.
A priority population for clinical trials in bariatric surgery is patients at high risk for cardiovascular disease, defined by age, co-morbidities, and pre-existing cardiovascular disease. Within this priority group, important sub-populations to include are patients with sleep disordered breathing, patients with asthma or related breathing disorders, and patients with heart failure including right sided heart failure and preserved systolic function heart failure. Preserved systolic function heart failure patients were considered an important group for initial focus. Small observation studies have demonstrated improvement in heart function after bariatric surgery. Given the high prevalence of obesity among preserved systolic function heart failure patients and the current limited treatment options, a trial in this population may provide significant benefit.
The members also felt strongly that future trials should include patients with a body mass index (BMI) as low as 30 kg/m2. Many patients at high risk for cardiovascular disease have a BMI between 30 and 35 kg/m2. Although not currently recommended, bariatric surgery has theoretical benefit for patients in this weight range.
No consensus was reached on the type of bariatric surgery to be tested (gastric banding versus gastric bypass). Although gastric banding is less invasive and more easily reversible, weight loss is slower and dependent on both the protocol used for band inflation and the adherence of the patients to those adjustments. Standardization of either surgical procedure to maintain the fidelity of the intervention was raised as an important consideration but may be easier to accomplish with gastric bypass. The optimal comparison group was felt to be a combination of intensive lifestyle treatment that included diet and exercise, and optimal medical care of all co-morbidities. Ideally, trial outcomes would be clinical: all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Other outcomes felt to be of significant importance were patient satisfaction, quality of life, healthcare utilization, surgical complications, and patient preference elicitation. Shorter length trials should focus on recognized surrogate or intermediate markers such as changes in cardiac morphology and function as measured on magnetic resonance imaging or echocardiography, atherosclerotic burden as measured by carotid intima-media thickness, exercise capacity as measured by such as V02 max, and sleep disordered breathing as measured by the apnea-hypopnea index.
Finally, the working group felt that support from private health care providers and Medicare would facilitate these studies. Centers from other countries may also be approached. These future trials should be multi-disciplinary and include investigators with expertise in surgery, cardiovascular disease, sleep disordered breathing, and clinical trials, among others. Additionally, the working group members encouraged continued collaborative efforts between interested institutes at National Institute of Health (NIH) and investigators to advance the science of bariatric surgery.
A full report is in preparation.
Last Updated: June 2011