S2-E61 – SPLENDOR Study Lead Author Discusses the Effect of Bariatric Surgery on MACE and LAGO

SPLENDOR Study Lead Author Discusses the Effect of Bariatric Surgery on MACE and LAGO
How much impact can bariatric surgery have on MACE and MALO? SPLENDOR shows and lead author Ali Aminian tells!

Lead author Dr. Ali Aminian of the Cleveland Clinic joins the Surfers to discuss the recent SPLENDOR Study, which focuses on the effects of bariatric surgery on Major Adverse Cardiovascular Events (MACE) and Major Adverse Liver Outcomes (MALO).

Stephen Harrison and Roger Green are joined by Fatty Liver Foundation President Wayne Eskridge.

Timestamps:
9:02 – Ali Aminian begins to discuss the SPLENDOR study

11:38 – Ali explains the dual study outcomes

13:31 – Wayne has the first comment, then Stephen asks about sub-populations. Ali notes that the small sample size of events limits the ability to do so.

16:25 – Stephen asks whether it will be a good idea to analyze for MACE and MALO together, rather than separately, and describes the large shift in trial enrollment thinking this might cause.

17:53 – Stephen asks whether the study explored renal disease in a cardio-hepatic context. Ali discusses why not

20:20 – Roger notes virtually identical declines in MACE (7.3%) and MALO (7.2%), asks whether patients in the trial exhibited both

23:30 – Ali shares preliminary analyses (not ye released) about the impact of bariatric surgery on disease outcomes. (CAN’T-MISS)

24:35 – Stephen notes that these numbers look similar to the placebo group in the cenicriviroc trial

26:19 – Ali comments that having 100 F4 patients does not provide much power for analysis. Stephen says it might be “25 times” what anyone else has.

28:51 – Ali asks Stephen whether he can envision new agents having the potential to drive regression in cirrhosis patients.

30:02 – Stephen describes a small, recently reported efruxifermin trial that appears to do so,

goes on to hypothesize that over time we will find a strategy

35:13 – Wayne worries whether “the siren song of surgery” will stop people from doing the hard behavioral work

35:59 – Ali: the problem is 40% obesity, 10% severe and until recently, no way to treat it. Expresses optimism and hope for semaglutide and the GLP-1s to come

38:10 – Roger asks how the coming double and triple agonists that report 20+% weight loss will compare to surgery in outcomes

38:49 – Ali: we need to do trials, but the effect should be the same. Stephen agrees

40:31 – Shardool Jain, Director of R&D at Altrix Bio, joins from the audience to ask if members can envision a time where bariatric surgery becomes first-line therapy for extremely obese patients

42:40 – Ali suggests it may make sense for severely obese patients with multiple weight-related morbidities, not otherwise

44:50 – Stephen asserts we do not have enough surgeons in the US to execute the strategy. His preference: solve challenges that will reduce adherence with the new weight-loss medicines

46:29 – Roger makes three points. 1 – surgery in cancer is not an early-stage strategy as Shardool suggests; 2 – from his own experience, diet and exercise can be exceptionally effective in the motivated patient; 3 – you get one shot at surgery, many at medication

47:31 – Diet conversation continues…

50:57 – Shardool and Stephen exit

51:04 – Ali addresses NIT issue by noting that when data for these first patients were generated in 2004, there were no practical NITs available

51:43 – Last question: the most powerful long-lasting effects of SPLENDOR

52:03 – Ali: 1. Obesity is the main driver in Fatty Liver Disease. 2. Well populated, well-followed populations may provide unique insights

53:29 – Wayne: “the guidance that the heart-liver axis can be affected so dramatically is something we can use” with patients

54:12 – Roger: 1. The forecaster says investment in double agonists and triple agonists becomes more attractive. 2. Advocate notes that weight loss can help patients all along the NASH spectrum

56:22 – Business section