"[CIRT and REDUCE-IT] may be the only two CVOTs with any relevance to apabetalone/BETonMACE reading out before BETonMACE top LINE reads out in Q1 2019."

Oops. This one wasn't on my radar, but reported out this morning. Astrazeneca's SGLT2 inhibitor dopagliflozin (Farxiga) reported top-line data today for its Phase III DECLARE-TIMI 58 CVOT trial. The two primary outcome measures listed on ClinicalTrials.gov were: 1) Time to first event included in the composite endpoint of CV death, MI or ischemic stroke; and 2) Time to first event included in the composite endpoint of CV death or hospitalization due to heart failure.

For outcome 1 (3-point MACE): "[Fewer] MACE events were observed with Farxiga for the other primary efficacy endpoint, however, this did not reach statistical significance."

For outcome 2 (CV death or hospitalization due to heart failure): "Farxiga achieved a statistically-significant reduction in the composite endpoint of hospitalisation for heart failure (hHF) or CV death"

Full data is expected to be reported at American Heart Association November 2018. However, my initial impression is that dopagliflozin (Farxiga) is inferior to the two other SGLT2 inhibitors that have completed CVOTs: empagliflozin (Jardiance, tested in EMPA-REG OUTCOME) and canagliflozin (Invokana, tested in CANVASS). Both EMPA-REG OUTCOME and CANVASS achieved significance on the 3-point MACE composite outcome, which Farxiga in DECLARE-TIMI 58 did not. We'll have to wait for the full data to see how much Farxiga reduced CV death. Recall, Jardiance in EMPA-REG OUTCOME achieved an amazing 38% reduction in CV death. Overall, my opinion is that Farxiga didn't perform as well in the CVOT releative to Jardiance and Invokana. But don't worry, all three carry the FDA warning of increased risk of Fournier’s gangrene, a flesh eating genital infection! A 4th SGLT2 inhibitor (Merck's ertugliflozin aka STEGLATRO) has an ongoing CVOT (VERTIS-CV) that reads out next year.

https://www.nejm.org/doi/full/10.1056/NEJMoa1504720

https://www.nejm.org/doi/full/10.1056/NEJMoa1611925

See also EndPoints News article: Trailing rivals, AstraZeneca offers a hit and a miss on key cardio study for SGLT2 diabetes drug Farxiga