Packer M et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med 2024 Nov 16; [e-pub].https://doi.org/10.1056/NEJMoa2410027

In the industry-funded SUMMIT trial (NCT04847557), investigators examined cardiovascular outcomes of tirzepatide — an agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors — over a longer period in patients with HFpEF and obesity.

The 731 study participants had elevated filling pressures or an elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and a heart failure exacerbation event within the prior 12 months or a decreased estimated glomerular filtration rate <70 mL/min/1.73 m2. They were randomized to once-weekly subcutaneous tirzepatide (up to 15 mg) or placebo for at least 52 weeks with a median follow-up of 104 weeks.

Compared with placebo, tirzepatide resulted in significantly fewer primary-endpoint events (adjudicated heart-failure worsening or cardiovascular death) — 10% vs. 15% (hazard ratio, 0.62) —

HOWEVER--Death from any cause WAS NO DIFFERENT! (hazard ratio, 1.25; 95% CI, 0.63 to 2.45) (Table 2 and Fig. S4).

ALSO-- Adjudicated worsening heart-failure event resulting in hospitalization, intravenous drugs in an urgent care setting, or intensification of oral diuretic therapy is great but not what we care about

If I just have to increase your oral meds is that really worsening heart failure or you just eating too much on thanksgiving day???

What do we care about here—

Hospitalizations—and worsening heart-failure event resulting in hospitalization —was 3.3% in tirzepitide and 7.1% in the control group.

Which is a difference of 4 percent and a NNT of 25 to prevent hospitalizatoins

The other primary endpoint was…Kansas city cardio questionnaire

and significantly greater improvement (by approximately 7 points) in the Kansas City Cardiovascular Questionnaire clinical summary score (assessed at 52 weeks). 

Interpreting the Kansas City Cardiomyopathy Questionnaire in Clinical Trials and Clinical Care: JACC State-of-the-Art Review | Journal of the American College of Cardiology

As will be developed further, a change of 5 points is considered to be a small but clinically important change, whereas changes of 10 and 20 points are considered moderate-to-large and large-to-very large clinical changes. 

On good RX – a two year script of terzep 15mg that was used in this study would cost around – 24,000 or roughly 1000$ per month.

That means we have to spend 2.4 million dollars to prevent 4 hospitalistzations from heart failure at 2 yrs!