Thread by @mbelshazly

1/ Today, at #ESCcongress2019 DAPA-HF trial showed amazing results. I love the complex story behind developing these novel #diabetes drugs and their impact on CVD so I'm going to share it in this tweetorial #cardiotwitter

2/ First let me start by sharing DAPA-HF results. Basically, in pts with HFrEF, Dapagliflozin (SGLT-2i) arm had 26% reduction in primary outcome & 18% reduction in CV death REGARDLESS of #diabetes. Link to tweet w/results thx to @rladeiraslopes

https://twitter.com/rladeiraslopes/status/1168162917306572800?s=20

3/ Pre 2008, the FDA approved anti-diabetic medications based on their ability to reduce biomarkers, glucose and A1C, without the need for clinical outcome trials. Basically, anything that lowers A1c in diabetics got approved

4/ In 2005, PPAR agonist Muraglitazar was approved based on favorable lipids/A1c, then a @JAMA_current meta-analysis of publicly available phase II,III data by Nissen, Wolski and @EricTopol showed increased MI/CV death. Bristol myers halts development jamanetwork.com/journals/jama/…

5/ In 2007, Nissen and Wolski @ClevelandClinic published a @NEJM paper using data from trials+@US_FDA website showing that Rosiglitazone caused ⬆️ MI & CV death. Rosiglitazone was the most widely sold oral hypoglycemic at that time.
nejm.org/doi/10.1056/NE…

6/ DRAMA around this landmark publication. GSK executives, manufacturer of Rosiglitazone, meet Nissen and try to convince him not to publish results and promise reanalysis/collaboration/etc... Nissen records the meeting wo their knowledge (legal in OH😁) nytimes.com/2010/02/23/hea…

6/ Congressional hearings, bla bla. Finally in 2008 the @US_FDA Endo & Met drug committee issues guidance document:
1- Establish indep CV outcomes committee for adjudication
2- Enroll high CV risk/existing ASCVD pts in anti-diabetic med trials
3- Neat stats (cont below)

7/
3- Pre-marketing, the upper bound of 95% CI should be <1.8 with a reassuring point estimate.
4- A postmarketing trial is recommended to show that the upper bound 95% CI is < 1.3.

Result -> since 2008, every novel anti-diabetic has undergone dedicated CV outcomes trial

8/ This tremendous effort by scientists & pursuit of unpublished public data (from pharma) + journals publishing safety data quickly + FDA guidance LED TO tremendous scientific advances that we couldn't even fathom at that time
Nice review: ncbi.nlm.nih.gov/pmc/articles/P…

9/ Since 2008, billions $$$ spent on worthy clinical trials + FDA oversight ➡️ several oral hypoglycemics proved safe and MOREOVER improved CV outcomes in high-risk diabetics and even NON-DIABETICS with CHF!! In fact, it may become standard of care in HF tx for everyone!

10/ Bottom line:
1- Ethics eventually➡️benefit, even if it takes time. Investment in evidence-based med➡️new science, better pt care and bigger ROI
2- Never underestimate the impact of data-driven observations. Report them!

Inspiring story for scientists and clinicians!!!