Thread by @NephJC

Would a new drug option for resistant hypertension get you excited? How about a superior trial design?

Time to learn about PRECISION - our twitter journal club had 720 tweets, but you can catch the highlights quickly with the regular #TenTweetNephJC thread👇

2/10
What did I miss?

We know we miss targeting many pathways that contribute to resistant hypertension, a condition with high cardiovascular morbidity.

Enter aprocitentan, a dual endothelin receptor antagonist, for it’s crack at a Phase 3 trial.

pubmed.ncbi.nlm.nih.gov/36356632/

3/10
1 tweet methods

✅ Multi-center, blinded, randomised, parallel-group

✅ Elaborate run-in (figure) to give all amlod + HCTZ + valsartan, and then exclude pseudoresistant hypertension

✅ Does adding aprocitentan to regime improve unattended automated office BP 🆚 placebo?

4/10
1 tweet results

🔹730 patients randomised

🔹Mean age 62, 63% on ≥4 antihypertensives, baseline office BP 153/88

🔹At 4 weeks = reduction of 15.3mmHg systolic for aprocitentan, versus 11.5mmHg reduction with placebo

5/10
A figure paints 1000 words

Also had proof of efficacy in ambulatory BP monitoring

6/10
Give me something clever to say

“The Achilles heel of endothelin receptor antagonists has been fluid retention & PRECISION followed suit, with uncomfortable rates of heart failure in the aprocitentan arm. Might co-prescription with a flozin mitigate these adverse events?”

7/10
Chat consensus?

1️⃣ Aprocitentan does work in resistant hypertension, proven by convincing trial design

2️⃣ uACR 30% reduction encouraging

3️⃣ BUT this was a trial against placebo, not spiro that we actually use 4th line, is cardioprotective, is inexpensive, is beloved

8/10
Quote of the fortnight!

I think everyone agrees with @goupil_remi - an antihypertensive as good as doxazosin is worth limited celebration…

9/10
I want more info

✅ Is it reasonable to expect proof of end organ benefit in resistant hypertension trials? Enjoy working through the sums in this fantastic thread by @ProfDFrancis


✅ Summary @thana_susan
nephjc.com/news/aprociten…

✅ VA @Sandyrvsdav

10/10
Final thoughts

✳️ For now, we’ll stick with spiro & flozins

➡️ Coming 20/21 Dec - Lancet again for MyTEMP, the largest ever trial in patients on haemodialysis, looking at CV outcomes with standard 🆚 cooled dialysate
pubmed.ncbi.nlm.nih.gov/36343653/

Tweetorial by @jamiekwillows