40% Reduction in Death and Major Cardiovascular Events Seen with Metabolic Surgery Vs. Usual Care

Metabolic surgery is associated with significantly lower risk of death and major cardiovascular events compared with usual care in patients with type 2 diabetes mellitus (T2DM) and obesity, according to a large matched-cohort study from Cleveland Clinic.

The research was presented Sept. 2 as a late-breaking study at the 2019 European Society of Cardiology Congress and simultaneously published by the Journal of the American Medical Association (JAMA).

“Metabolic surgery has been clearly shown to significantly improve cardiometabolic risk factors, but its impact on major cardiovascular outcomes hasn’t been well characterized,” says lead author Ali Aminian, MD, a bariatric surgeon in Cleveland Clinic’s Digestive Disease & Surgery Institute. “That’s why we undertook this investigation.”

“Cardiovascular complications from type 2 diabetes and obesity can be devastating, so we are encouraged by these findings,” adds the study’s senior author, Steven Nissen, MD, Chief Academic Officer of Cleveland Clinic’s Miller Family Heart & Vascular Institute.

Matched-cohort study design

The researchers reviewed the records of all adults with T2DM managed at Cleveland Clinic from 1998 to 2017 (N = 287,438) to identify those — 2,287 in total — who underwent metabolic surgery at Cleveland Clinic. These surgical patients were then matched on a 1:5 basis to nonsurgical patients who had obesity (body mass index [BMI] ≥30 kg/m2), yielding a control group of 11,435 patients.

Nonsurgical controls were matched according to index date, gender, age, BMI, location of treatment facility, insulin use and presence of T2DM-related complications.

The primary endpoint was occurrence of a composite of six outcomes through the end of 2018:

• Coronary artery events (unstable angina, myocardial infarction [MI] or coronary intervention/surgery)
• Cerebrovascular events (ischemic stroke, hemorrhagic stroke or carotid intervention/surgery)
• Heart failure
• Atrial fibrillation
• Nephropathy
• All-cause mortality

Secondary endpoints included each of the six individual components of the primary endpoint and a three-component major adverse cardiovascular events (MACE) composite endpoint (all-cause mortality, MI and ischemic stroke).

Cumulative incidence estimates for 8 years from the index date were calculated for each outcome, as were multivariable Cox regression analyses.

Results in brief

By the end of the study period, which reflected median follow-up of 3.9 years (interquartile range, 1.9-6.1 years), the primary endpoint occurred in 385 patients in the surgical group and 3,243 patient in the nonsurgical control group. This translated to a cumulative incidence at 8 years of 30.8% in the surgical group versus 47.7% in the nonsurgical group (P < 0.001), for an absolute risk difference of 16.9% and an adjusted hazard ratio (HR) of 0.61 (95% CI, 0.55 to 0.69).

Metabolic surgery was likewise associated with significantly lower rates of all secondary endpoints relative to usual care, including each of the six components of the primary endpoint and the three-component MACE composite endpoint. Adjusted HRs for metabolic surgery were as follows for two secondary endpoints of particular interest:

• All-cause mortality, HR = 0.59 (95% CI, 0.48-0.72)
• Three-component MACE, HR = 0.62 (95% CI, 0.53-0.72)

Moreover, statistically significant reductions in weight, glycated hemoglobin (HbA1c), and use of diabetes and cardiovascular medications were observed in the metabolic surgery group relative to the control group.

Bottom line: Findings are robust but not definitive

“The striking reductions of major adverse cardiovascular events observed after metabolic surgery in this study are likely related to patients’ substantial and sustained weight loss,” observes Dr. Aminian. “However, recent evidence suggests that some of the metabolic benefits of surgery in patients with diabetes may be attributable to anatomical changes in the gastrointestinal tract that are independent of weight loss.”

The authors note that their study has a number of strengths, including its large sample size and comprehensive statistical analysis, the fact that it included some patients with mild and moderate levels of obesity, and its near-exclusive focus on patients undergoing contemporary metabolic surgery procedures. On the latter point, 95% of surgical patients underwent either Roux-en-Y gastric bypass (63%) or sleeve gastrectomy (32%). Furthermore, adverse events of metabolic surgery were examined. “Although we observed some early and long-term complications after surgery in this study, metabolic and bariatric surgical intervention was associated with a 41% reduction in mortality in surgical patients,” says Dr. Aminian.

The authors also acknowledge the limitations of the study’s observational design and note that these findings must be viewed as hypothesis-generating.

“Now that we have seen these robust observational results, a well-designed randomized controlled trial is needed to definitively determine whether metabolic surgery can reduce the incidence of major cardiovascular complications in patients with type 2 diabetes and obesity,” notes Dr. Nissen.