Month: December 2017

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My SGLT2 inhibitor grand-rounds lecture

This past autumn I was invited to give a lecture at the Michigan ACP. I love that meeting. I decided to talk about the mortality data on SGLT2 inhibitors and how we got that data and how curious that data is. Then, last week I had the opportunity to give the lecture again for grand rounds at St John Hospital and Medical Center. Here it is in 4 chapters:

Chapter 1: The History and top line CV outcomes

Chapter 2: What’s driving the improvement in outcomes?

Chapter 3: Renal outcomes

Chapter 4: Side effects and conclusions

Here is the Keynote presentation for your editing pleasure: Keynote (278 mb)

In response to chapter 2, Matt Sparks had this interesting tweet:

This brings up an important point. One of the most intriguing slides is the one below that looks at how long it takes for the Kaplan-Meier to separate.

With glycemic control and blood pressure interventions, their is notable lag, but with the SGLT2i drugs the lines diverge from the very first dose. We also see that pattern with ACEi in heart failure and aldosterone antagonists in heart failure. This may be a clue of where to look for the cause of the survival advantage.

RALES (3 months)

CONSENSUS (first dose)

I will be adding this slide to the next version of the talk.

 

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List of therapies that reduce cardiovascular mortality in diabetes

I’m giving grand rounds on Tuesday on SGLT2 inhibitors and I’m trying to come up with a list of therapies that lower CV death in diabetes.

Here is my list:

  • Blood pressure control
    • UKPDS
    • ADVANCE All-cause mortality was reduced with a near miss on CV mortality (P=0.041)
  • Empagliflozen
  • Canagliflozin
    • CANVAS Only partial credit here. CV death was part of the composite outcome, but CVD was not significant on its own
  • Semaglutide
    • SUSTAIN-6 Weak. Hit the primary outcome but CV death was explicitly identical between groups
  • Liraglutide

Drugs that have run the FDA CV disease gauntlet and that are non-inferior to standard of care:

  • Exanatide
  • Rosiglitazone
  • Pioglitazone
  • Alogliptin
    • EXAMINE (This is a secondary prevention trial. As far as I can tell it is the only FDA mandated outcome trial that is specifically designed as a secondary prevention. Not sure why.)
  • Saxagliptin
  • Degludec

 

I’m sure I’m missing some. There must be a statin trial of diabetics. Right?

 

Swapnil was first with the statin answer:

And Edgar came up with a great visual from a review paper:

And Szymon came up with the Steno trial. I can’t believe I forgot about that one.

 

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NephTalk: A new nephrology podcast by Satellite Health

Satellite Healthcare is a non-for-profit dialysis company. They partnered with NephJC to do Bloggger’s Night the last three years and sponsor the NephJC Kidneys. This year they launched a Podcast, NephTalk. I was lucky to get invited to help out. I have hosted one, an interview with Sumi Sun about preventing blood stream infections. Here is her abstract from Kidney Week:

Background: CVCs are associated with catheter-related bloodstream infection (BSI) resulting in increased morbidity and mortality. Following our report of significantly reduced infection when 320 μg/mL gentamicin in 4% citrate is used as the CVC locking solution (Moran AJKD 2012), this has remained the standard of care in patients dialyzing with a CVC, unless physician order requested otherwise. The infection rates were monitored through an internal QC program developed for National Healthcare Safety Network (NHSN) reporting.

Methods: This study evaluated NHSN data with self-reported infection rates from January 2014 to December 2016 in a non-profit dialysis provider with a total of 57 free-standing dialysis facilities serving more than 5000 HD patients. BSI was reported according to NHSN criteria. Data were audited through comparison to an internal infection control report and discrepancies reconciled prior to final NHSN submission. Blood cultures were mandated before any antibiotic administration for suspected BSI, and 85% or more are sent to one internal lab (Ascend).

Results: The rate of catheter-related bloodstream infection over the three years was 1.00 episodes/100 patient months, 54% lower than the national average of 2.16 for CVC-related BSI (2014 NHSN BSI Pooled Mean Rate/100 patient-months). Monthly BSI rates showed minor fluctuations, however none exceeded the national average in any given month.

Conclusion: Gentamicin 320 μg/mL in 4% sodium citrate as a routine catheter lock demonstrated sustained low CVC-related BSI rates in HD patients, with approximately half the infection rate compared with the national average. Gentamicin-citrate lock should be considered the standard of care in patients with CVC access.

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PodCast: Curbsiders #69

I was invited by the Curbsiders to talk about CKD. The discussion went a little long and our discussin got divided into two podcasts, #67 and #69. Here is the second half. I don’t think I made any major mistakes except when discussing combined ACEi and ARB therapy I said ALTITUDE was a study of RAAS inhibtion and endothelin antagonists. Actually ALTITUDE was RAASi and Aliskiren, the direct renin antagonist. And it was stopped not because of hyperkalemia but due to a CV signal (though the combination did have more hyperkalemia). The trial I was thinking about was ASCEND which added the endothelin antagonist avosentin to an ACEi or ARB in patients with diabetic nephropathy. This trial was also stopped early, again for CV issues after only 4 months on the drug!

You can listen to the episode here.