Gregg Fonarow MD

[Gregg Fonarow MD @gcfmd]

❤️‍🩹 Heart failure

💊 SGLT inhibitors

🚀 Ultrafast clinical benefits (across the EF spectrum)

🪎 Amazing value

🛎️ What are you waiting for?

[JAMA Cardiology @JAMACardio]

Among statin-intolerant adults at high cardiovascular risk, #BempedoicAcid was associated with reduced risk of #VenousThromboembolism, including deep vein thrombosis and pulmonary embolism.

https://t.co/AOeVP2X8Xt

[Gregg Fonarow MD @gcfmd]

@ShahzebKhanMD @JavedButler1 @f2harrell Congratulations @ShahzebKhanMD

We conceived of this approach for ASCVD therapy in 1994, evaluated in UCLA CHAMP: ⬆️ use, adherence, outcomes (GWTG)

Proposed for quadruple GDMT in HFrEF in 2020 with @SJGreene_md + @JavedButler1 with subsequent RCTs

Look forward to your results

[European Society of Cardiology Journals @ESC_Journals]

🫀Adipokine Profile in Acute Heart Failure: Associations with Natriuretic Response and Prognosis. see @ESC Heart Failure https://t.co/UmJXqCG8T9

@EJHFEiC @JanBiegus @Ppponikowski #HFA_ESC @hvanspall @ShelleyZieroth @FudimMarat @gcfmd @MarcoMetra @GianluSava #ESCHeartFailure

[Gregg Fonarow MD @gcfmd]

@echo_batman @maybeadoc1983 @drjohnm The comparator solely guided by the evidence

For HFrEF, evidence/guidelines supported ACEI over ARB. If an ARB was selected would have been criticized since ARB had failed in RCTs to be non-inferior to ACEI

In HFpEF, ARB > ACEI. PARAGON-HF S/V vs valsartan 160 mg bid tested

[Gregg Fonarow MD @gcfmd]

@djc795 @AnilMakam The powerful life-prolonging benefits associated with high adherence to placebo!

[Gregg Fonarow MD @gcfmd]

@PLooserMD @naderjo @drjohnm Unblinded, ⬆️ SAE rates, small # of centers over 10 years, p=0.04, and yet the DSMB recommended to permanently stop 2nd RCT

Now what if the trial had been 10x larger, double blinded, SAEs less than control, RRR for CV☠️ similar magnitude ⬇️, and p=0.00008

Still require 2nd RCT?

[Gregg Fonarow MD @gcfmd]

An adequately powered RCT to evaluate similar outcomes as PARADIGM-HF would cost ~$300 to $450 million

You would need patients willing to volunteer/consent, investigators willing to randomize, and IRBs willing to approve

When most across the world already see ARNI as Class 1 https://t.co/iwjv0Y4wBe

[JAMA Cardiology @JAMACardio]

Among patients with #Type2Diabetes and #ChronicKidneyDisease, finerenone reduced risks of cardiovascular and kidney events and promoted regression of #CKM syndrome regardless of baseline stage. https://t.co/jHZraJspjN

[Gregg Fonarow MD @gcfmd]

Any interest in providing clinical benefits to millions of eligible patients

While also reducing net healthcare expenditures by $24.5 billion a year

[Gregg Fonarow MD @gcfmd]

@JavedButler1 @kejoynt @AnnMarieNavar @NilayShahMDMPH @boback @NealDixit @DrMarthaGulati @paheidenreich @ATSandhu @NMHheartdoc Which other healthcare interventions would have a 8-fold or more return on investment?

Invest $3.5 billion to supply SGLT2i to the 47.5 million eligible patients with T2DM, CKD, or HF in the US annually

Get $27.6 billion reduction in healthcare expenditures annually

Nice

[Philipp Doc @GamerPhilDoc]

@gcfmd @CircOutcomes @jasonwasfy @kardiologykazi @laurapco Anyone else here see how generic pricing inverts the value equation in HF? SGLT2i and ARNI just shifted from high cost to cost-dominant almost overnight.

[Gregg Fonarow MD @gcfmd]

@crowanmd @drjohnm Concur

Primary endpoint met non-inferiority but not superiority (HR 0.94, 95% CI 0.86-1.03)

Secondary endpoint: ☠️ or CV 🏨 HR 0.91 [95% CI, 0.84 to
0.99]), P=0.024

The authors’ conclusions:

[Gregg Fonarow MD @gcfmd]

@CircOutcomes @jasonwasfy @kardiologykazi @laurapco Timing and drug pricing is everything

In 2026, with low cost generic pricing SGLT2i and ARNI are cost saving (cost dominant) to ICER <$5,000 per QALYs saved in HF

[Gregg Fonarow MD @gcfmd]

@ESC_Journals @EJHFEiC @AmrAbdin10 @GiuseppeGalati_ @HanCardiomd 🚧 Global gaps in implementation

🎯 Global implementation of quadruple GDMT for HFrEF

➡️

❤️‍🩹 1.2 million ☠️s prevented annually

✅ Overcome inertia to meet the challenge

[European Society of Cardiology Journals @ESC_Journals]

🌍 Heart failure affects > 64 million people worldwide + remains a major global health challenge.
👉This review summarizes the latest data on HF epidemiology, trends, and future challenges.
https://t.co/xJipGll9Or

@EJHFEiC @AmrAbdin10 @GiuseppeGalati_ @HanCardiomd

[Gregg Fonarow MD @gcfmd]

@naderjo @drjohnm No RCT MI+cardiogenic shock

➡️

DanGer Shock: 14 centers, 355 patients, 185 events, p=0.04

➡️

RECOVER IV terminated following DanGer +results

DSMB: equipoise no longer exists

Recommended permanent discontinuation

Judged unethical to keep randomizing to a no-Impella arm

[Gregg Fonarow MD @gcfmd]

@Sensible__Med @AnilMakam 🤣

Contrived with no valid basis to assert enalapril 10 mg bid is sub therapeutic or that any dose of valsartan is a more valid comparator. Playing games as if HFpEF and HFrEF are the same.

Hopefully can do something better with “appraisal” than this

[Gregg Fonarow MD @gcfmd]

@crowanmd @drjohnm The OVERTURE trial was not powered for CV☠️ but showed the potential for neprilysin inhibition in HFrEF

A better agent (S/V) w/ less angioedema risk was developed

Tested in PARADIGM-HF

Proven to
⬇️ CV☠️/HF🏨
⬇️ CV☠️
⬇️ AC☠️

As well or better tolerated vs enalapril

[Gregg Fonarow MD @gcfmd]

@crowanmd @drjohnm Here is the meta-analysis which includes IMPRESS, OVERTURE, and PARADIGM-HF in HFrEF

⬇️ CV☠️/HF🏨

⬇️ AC ☠️

Combined neprilysin/RASi, 2 agents, 3 trials ➡️ benefit in HFrEF

OCTAVE was 24 week hypertension trial for BP control and Angioedema rate. Not CV events.

[Gregg Fonarow MD @gcfmd]

@AnilMakam It was a double blind RCT, not open label

Tested vs a gold standard agent/dose

The run in was shown to have no impact on efficacy, even if excluded pts imputed back in

And then need to write off PIONEER-HF with no run in, conducted by the TIMI group as also somehow biased

[Gregg Fonarow MD @gcfmd]

@drjohnm PS:

In PREVAIL there were n=33 primary endpoints at 26 month mean f/u

Compared to PARADIGM-HF of n=1251 CV ☠️ endpoints

20% RR ⬇️ vs ACEI control, p=0.00008

Not all “just one” trial are the same in terms of strength and meeting FDA criteria for “substantial evidence”