Deepak Bhatt, MD, MPH on why debating which SGLT2 inhibitor is best for heart failure patients is “missing the bigger picture.”

Cardiology Pharmaceuticals

Lexicon’s Lands Long-Awaited HF Approval

Lexicon Pharmaceuticals’ Inpefa (sotagliflozin) just became the first FDA-approved dual SGLT2 / SGLT1 inhibitor for treating heart failure, landing a wide-ranging approval that could alter the HF treatment arena.

The once-daily pill is approved for risk reduction of cardiovascular death, heart failure hospitalization, and urgent heart failure ED visits among all adults with HF — regardless of their diabetes status or left ventricular ejection fraction range (including HFpEF and HFrEF). 

• Inpefa also uniquely inhibits SGLT1 (responsible for glucose absorption in the GI tract) and SGLT2 (responsible for glucose reabsorption by the kidney).

Inpefa’s approval for such a broad range of patients is largely supported by the results of two Phase 3 trials:

• The SOLOIST-WHF trial showed that sotagliflozin reduced the risk of CV death, HF hospitalization, and urgent HF visits by 33% compared to placebo
• In the SCORED study, sotagliflozin similarly reduced the composite risk of CV deaths, HF hospitalizations, and urgent HF visits (HR 0.74).
• The trials also showed that sotagliflozin might uniquely improve glycemic control at lower GFRs, while reducing risk of stroke and nonfatal heart attacks.

Still, sotagliflozin’s path towards FDA approval was far from easy, including a 2019 rejection for treating Type 1 diabetes (that prompted Sanofi to terminate their partnership) and Lexicon’s 2022 decision to temporarily rescind its FDA application for treating HF in patients with Type 2 diabetes. 

Lexicon’s regulatory perseverance should pay off commercially when Inpefa launches later this month, which with the help of a new $125M public stock offering, would likely drive a massive surge in sales (compared to its $139k in 2022 revenue, anyway).

Inpefa will face plenty of SGLT2 competition from AstraZeneca’s Farxiga (dapagliflozin) and Eli Lilly and Boehringer Ingelheim’s Jardiance (empagliflozin), which brought in a combined $10.6B last year, perhaps placing more emphasis on Inpefa’s unique ability to also inhibit SGLT1.

HF advocates will also be monitoring whether the introduction of a third HF medication might create enough competition to drive down SGLT2 medication costs and boost still-lagging adoption. That said, Lexicon plans to start Inpefa with pricing “comparable to existing heart failure medications,” so they shouldn’t expect any immediate reductions.  

The Takeaway

Cardiology’s red hot heart failure care segment just added its third medication covering all HF patients, and its first supporting both SGLT1 and SGLT2 inhibition. That could be a big deal for HF patients and clinicians in search of more treatment options (and eventually more reasonable costs), and for Lexicon Pharmaceuticals’ commercial ambitions.

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The Wire

• A Case for NT‐proBNP Screening: Johns Hopkins researchers found that NT‐proBNP levels are a strong predictor of mortality in the general population, suggesting that NT‐proBNP could be used to screen for future CVD risks. Analysis of 10,645 individuals without prior CVD over a 17.3-year median follow-up period showed that people with NT‐proBNP levels in the ≥75th percentile had significantly higher risks of all‐cause and cardiovascular mortality than those in the <25th percentile (hazard ratios: 1.67 & 2.87).

• Plant-Based CVD Benefits: Following vegetarian or vegan diets lowers atherogenic cholesterol by 14%, amounting to a 20% reduction in ASCVD risks if maintained over 15 years. That’s one of the key takeaways from a massive systematic review of 30 randomized trials held between 1982 and 2022, which found that people on plant-based diets experienced far greater reductions in total cholesterol, LDL cholesterol, and apoB levels compared to those on omnivorous diets (-7%, -10%, -14%).

• Vivalink’s 14-Day ECG Patch: Wearable remote monitoring company Vivalink launched a new ECG monitoring patch that supports a “continuous 14-day live stream” per patch application, with the goal of reducing both clinician and patient burden. Intended for ambulatory use such as post-op monitoring, the patch complements its real-time ECG feed with a range of other data points (e.g. HRV, respiratory rate, skin temperature, step count & activity, and posture detection).

• UTSW’s Heart Regeneration Grant: UT Southwestern Medical Center’s ongoing research into heart regeneration will receive a $10.7M boost from the NIH. The five-year grant will support research into how the immune system regulates the heart’s ability to regenerate and repair itself after cardiac events, building upon discoveries from previous UTSW studies. If successful, the research could lead to new therapeutic targets for heart failure treatments.

• NI006’s ATTR Cardiomyopathy Promise: A recent phase 1 trial suggests that the NI006 antibody can safely and effectively reduce cardiac amyloid load and alleviate heart failure. The trial had 40 patients with ATTR cardiomyopathy receive either NI006 or a placebo for four months, finding that the NI006 patients had no serious adverse events, while those taking at least 10 mg/kg of NI006 showed reduced cardiac amyloid imaging markers through 12 months. These results had some physicians on MedTwitter forecasting that N1006 could be the next big thing for ATTR cardiomyopathy.

• ProScan Adds Cleerly CCTA AI: Cleerly announced a strategic partnership with major outpatient imaging group ProScan (33 imaging centers in five states), which will use Cleerly’s AI-enabled platform to analyze CCTA exams and help radiologists and cardiologists identify, characterize, and qualify atherosclerosis buildup, while supporting more precise diagnosis. The announcement comes just a few weeks after Cleerly similarly launched at Los Angeles practice, Apex Cardiology.

• Sacubitril/Valsartan Beats Valsartan-Only After HF Events: The PARAGLIDE-HF trial suggests that sacubitril/valsartan may deliver greater benefits to patients with ejection fraction over 40% after a recent worsening HF event compared to valsartan alone. In the trial (n=466), sacubitril/valsartan improved NT-proBNP levels more than valsartan (ratio of change: 0.85) and reduced worsening renal function (OR: 0.61). However, sacubitril/valsartan-takers did show higher rates of hypotension and some experts seemed skeptical about these results.

• Omnipolar Voltage Excel in AF Scar Assessment: In cases of AF, omnipolar voltage (OV) maps assess atrial voltage better than bipolar voltage (BV) maps. A JACC study comparing 40 de novo and repeat ablation procedures revealed a consistently smaller proportion of left atrium area occupied by low-voltage zones (LVZs) on OV maps than BV maps (42.4% vs. 66.7%). OV maps aligned better with BV sinus rhythm maps and were more accurate in spotting gaps on wide area circumferential ablation lines at pulmonary vein reconnection sites.

• Cath Lab Malpractice Verdict: An Indiana woman was awarded $2.67M in malpractice damages after a botched cath lab procedure and insufficient follow-up left her with a significantly weakened and disfigured right leg. Her cardiologist was found to have mishandled a new interventional device, leaving a polymer in her right femoral artery, and then did not call the patient in for further evaluation after she reported intense pain. The polymer traveled to another artery and became lodged, causing blood clots and requiring follow-up surgery.

• Predicting Readmissions: A Nature study found that adding remote patient monitoring data from smartphones or wearables improves standard models for predicting 30-day hospital readmissions. An enhanced prediction model with both physical activity and sleep pattern data increased AUCs from 0.63 to >0.80, with data from just wearables only slightly outperforming smartphone data in the best models (AUCs: 0.85 vs 0.84). Many patients in the study were admitted with cardiology-related issues (e.g. MI, CHD, HF).

• BrightHeart’s Fetal Heart AI: Paris-based ultrasound AI startup BrightHeart launched to help clinicians catch the 70% of congenital fetal heart defects that go undetected. BrightHeart will use €2M in seed financing and a database of over 20k fetal ultrasound exams to further develop its AI technology, which helps clinicians detect complex fetal heart defects during screening exams. BrightHeart will also use the funds to prepare its regulatory submissions and facilitate the company’s expansion.

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