Deepak Bhatt, MD, MPH, MBA

Pacibekitug outperformed placebo in reducing hs-CRP, Lp(a), and other inflammatory biomarkers in patients with 

 during the TRANQUILITY trial; however, without being powered for 

, the question of this drug’s efficacy in risk reduction still remains.

Next Steps for Pacibekitug Following Positive TRANQUILITY Results

The data from TRANQUILITY were presented at the 

European Society of Cardiology (ESC) Congress 2026

 in Munich, Germany, by Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai. In an exclusive interview, 

 breaks down the results and investigators’ plans for a phase 3 trial of pacibekitug for cardiovascular events.

“This trial was meant to be a proof of principle, that the drug does what it’s supposed to – safely lowering hs-CRP in the context of a modest-size phase 2 trial,” Bhatt told 

. “For the phase 3 trial planning, we were really never considering CKD because that’s a tough population. Things that have worked in other non-CKD populations for cardiovascular risk reduction haven’t always worked in advanced kidney disease.”

TRANQUILITY, a randomized, double-blind, placebo-controlled study evaluating pacibekitug administered quarterly and monthly to patients with CKD and elevated hs-CRP, enrolled patients with a serum hs-CRP level ≥2.0 mg/L and <15 mg/L and a diagnosis of CKD, among other criteria. These patients were randomly assigned in a 1:1:1:1 ratio to either pacibekitug 25 mg or 50 mg every 90 days, 15 mg every 30 days, or placebo.

The primary endpoint was time-averaged percent change from baseline in hs-CRP by day 90. Secondary endpoints included time-averaged percent change in hs-CRP through day 180, the proportion of patients with time-averaged hs-CRP <2 mg/L at 90 days, and the safety and tolerability of pacibekitug.

A total of 143 patients were enrolled, of whom 72% were receiving statins and 59% had diabetes. Bhatt and colleagues noted dose-dependent reductions in hs-CRP by day 30, which were sustained through 180 days. The median time-averaged change was -76% with pacibekitug 25 mg, -85% with 50 mg, and -89% with 15 mg, compared to +7% with placebo. Fibrinogen and Lp(a) also saw sustained reductions in the pacibekitug arms, and no dose-related safety signals were recorded.

However, the trial itself was not powered to detect cardiovascular outcome improvements. Given the additional reductions in Lp(a), coupled with inflammation’s direct influence on cardiovascular disease risk, Bhatt believes that further data from ongoing trials will determine whether these targets are associated with cardiovascular benefit. On the other hand, inflammation is a notoriously narrow window to target – past trials, including CANTOS and ZEUS, have indicated the risk of increased fatal infection if inflammation is too significantly reduced and the lack of cardiovascular benefit if the effect is too small.

“The inflammation story is ongoing,” Bhatt said. “There are a number of trials in different therapeutic areas, and lots of different companies planning trials with various anti-inflammatory agents, phase 2 trials, phase 3 trials, ongoing in the planning stages. We’ll see whether that is also an independent axis of risk reduction. But for now, Lp(a) reduction, hs-CRP reduction, and a broader reduction of arterial inflammation all seem like promising approaches to study.”

Editor’s Note: Bhatt reports disclosures with GSK, Merck, Cereno Scientific, Angiowave, Boehringer Ingelheim, Novo Nordisk, and others.

Bhatt D. TRANQUILITY: Efficacy of monthly and quarterly dosing of pacibekitug (IL-6 ligand mAb) targeting inflammation in CKD with high cardiovascular risk. Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

Tourmaline Bio. A Study to Evaluate TOUR006 in Patients With Chronic Kidney Disease and Elevated Hs-CRP (TRANQUILITY). ClinicalTrials.gov Identifier: NCT06362759. Updated August 11, 2026. Accessed September 4, 2026. 

https://clinicaltrials.gov/study/NCT06362759

Videos

Deepak Bhatt, MD, MPH, MBA, discusses the next steps for pacibekitug in cardiovascular disease following its success in the phase 2 trial.

Pacibekitug, an investigational interleukin-6 (IL-6) antibody, substantially reduced inflammatory biomarkers in patients with 

 at high inflammatory risk during the phase 2 TRANQUILITY trial.

TRANQUILITY: Pacibekitug Reduces hs-CRP, Inflammatory Biomarkers in CKD

 in Munich, Germany, by Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai.

“Overall, in the context of a phase 2 trial, I would say it was a positive trial,” Bhatt told 

 in an exclusive interview. “Of course, the trial wasn’t powered for 

. That’s what would need to come next: a phase 2 trial in the right population to see if this approach of targeting inflammation with IL-6 inhibition reduces adverse cardiovascular outcomes.”

TRANQUILITY was a randomized, double-blind, placebo-controlled study evaluating quarterly and monthly pacibekitug dosing among patients with CKD and elevated high-sensitivity C-reactive protein (hs-CRP). Patients were eligible if they were ≥18 years of age with a serum hs-CRP level of ≥2.0 mg/L and <15 mg/L, as well as a diagnosis of CKD. Patients with a history of immunodeficiency, gastrointestinal ulceration or perforation, or active diverticulitis, among other criteria, were excluded.

Enrolled patients were randomly assigned in a 1:1:1:1 ratio to receive subcutaneous pacibekitug 25 or 50 mg every 90 days, 15 mg every 30 days, or placebo, all over 6 months. The primary endpoint was time-averaged percent change from baseline in hs-CRP through day 90. Secondary endpoints included the proportion of patients with time-averaged hs-CRP <2 mg/L at 90 days, time-averaged percent change in hs-CRP from baseline through day 180, and the safety and tolerability of pacibekitug, among others.

A total of 143 patients were included, with a mean age of 69 years. 72% of the enrolled patients received statins, and 59% had 

. By day 30, pacibekitug treatment had resulted in dose-dependent decreases in hs-CRP – these reductions were sustained through 180 days. Median time-averaged change in hs-CRP was +7% with placebo, -76% with pacibekitug 25 mg, -85% with 50 mg, and -89% with 15 mg (all 

<.0001 vs. placebo). Additionally, Bhatt and colleagues noted substantial and sustained reductions in fibrinogen and Lp(a), as well as other inflammatory markers, across all 3 pacibekitug groups.

Ultimately, Bhatt and colleagues concluded that pacibekitug treatment efficaciously reduced hs-CRP in this patient population, with only 1.9% of patients discontinuing treatment and none reporting clear dose-related safety signals. However, Bhatt also acknowledges the lingering question of actual cardiovascular outcome improvements, given that the trial was not powered to examine this endpoint.

“Ongoing trials with other agents will see whether drugs specifically targeting Lp(a) and reducing Lp(a) are associated with cardiovascular benefit or not,” Bhatt said. “These results will be coming out, I imagine, relatively soon, likely before the end of the year. I think that the bolus of data that we’ll get in the next year or 2 about Lp(a) reduction strategies and whether they reduce cardiovascular events will tell us a lot.”

Editors’ Note: Bhatt reports disclosures with GSK, Merck, Cereno Scientific, Angiowave, Boehringer Ingelheim, Novo Nordisk, and others.

Deepak Bhatt, MD, MPH, MBA, discusses the efficacy of this investigational IL-6 antibody among patients at high inflammatory risk.

Plaque Imaging and the TRANSFORM Trial in Myocardial Infarction

Acute coronary syndrome (ACS), and more specifically 

, is among the most life-threatening diseases in the US, affecting roughly 1,045,000 patients annually. In addition to mortality, the condition contributes to a significant economic and health care burden.

However, a significant proportion of patients with MI do not exhibit common identifiable risk factors, and many are not provided with the necessary therapies to forestall negative outcomes. Many patients are only treated after coming to the clinic with apparent symptoms, which naturally leaves many patients without treatment.

At the American Society of Preventive Cardiology (ASPC) 2026 Virtual Imaging Symposium, Deepak Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai, spoke on plaque progression and regression as an imaging endpoint for MI.

“There’s been a tremendous amount of progress that’s been made in cardiology – we have terrific biological insight into what causes myocardial infarction, heart attacks,” Bhatt told 

. “But about 1 in 5 patients don’t have any identified risk factors. Some of them maybe have risk factors, but they weren’t identified as such. About 1 in 5 didn’t have any prior physician visits, and a majority – about 2/3 – weren’t on any preventive therapies, though they should have been. That’s the state of primary prevention right now in the US – it’s not really effective.”

In his presentation, Bhatt addressed the limitations of current risk analysis for asymptomatic patients, highlighting a variety of potential methods of screening to catch ACS before it progresses. In addition to plaque analysis, Bhatt also highlights cholesterol, triglycerides, lipoprotein(a), and residual diabetes as red flags for ACS progression, proposing potential interventions for each.

The leading pathological cause of ACS and, by extension, MI, is plaque rupture – several previous studies since 1980 have confirmed that plaque rupture is found in many of the most fatal MI cases. More recent decades have seen progress in utilizing imaging to identify precursor lesions that could progress to ACS, and investigators have hypothesized that local therapeutic interventions could prevent plaque rupture-induced thrombosis.

Experts are currently investigating plaque screening methods in patients with MI through the TRANSFORM trial, which is a prospective, randomized, open-blinded endpoint (PROBE), event-driven, pragmatic trial in patients at increased risk of 

 without known symptomatic cardiovascular disease. The trial will implement the Cleerly Coronary Artery Disease (CAD) Staging System to identify asymptomatic patients and personalize treatment to avoid cardiovascular events.

Bhatt expressed interest in the TRANSFORM trial, emphasizing the value of finding an effective method of screening for MI that will prevent the loss of traditionally asymptomatic patients. However, while Bhatt does support further screening tests in MI, he also addresses the inherent risks of implementing the technology early. Further testing is required to validate these devices and to determine their overall effectiveness.

“A lot of times, there can be a promising technology, and if you introduce it too soon, before there is the technical sophistication, the interpretive expertise, it doesn’t work,” Bhatt said. “The other risk is the Pandora’s box idea; that is, you don’t want to adapt a technology too soon, even though it’s intuitively appealing.”

Młynarska E, Czarnik W, Fularski P, Hajdys J, Majchrowicz G, Stabrawa M, Rysz J, Franczyk B. From Atherosclerotic Plaque to Myocardial Infarction-The Leading Cause of Coronary Artery Occlusion. Int J Mol Sci. 2024 Jul 2;25(13):7295. 

Bhatt D. Plaque Progression/Regression as a Treatment Target: Imaging Endpoints that Matter. Presented at the American Society of Preventive Cardiology 2026 Virtual Imaging Symposium, May 1, 2026. 

https://www.youtube.com/watch?v=t341F439OXI

Cleerly, Inc. A Randomized Comparison of Stage-Based Care Versus Risk Factor-Based Care for Prevention of Cardiovascular Events (TRANSFORM). ClinicalTrials.gov Identifier: NCT06112418. Updated May 20, 2026. Accessed May 20, 2026. 

https://clinicaltrials.gov/study/NCT06112418

Deepak Bhatt, MD, MPH, MBA, discusses his recent presentation at the ASPC 2026 Virtual Imaging Symposium and how plaque imaging can change the MI landscape.

Dr. Deepak Bhatt highlights 4 trials to watch in the late-breaking sessions at ACC.26.

ACC.26 Late-Breakers to Watch, With Deepak Bhatt, MD, MPH, MBA

As the cardiovascular community prepares to convene in New Orleans for the 

American College of Cardiology’s Annual Scientific Session & Expo (ACC.26)

, attention is once again turning to the late-breaking clinical trials expected to define the meeting’s scientific and clinical impact.

Each year, these presentations serve as a bellwether for where cardiovascular care is headed, often introducing data directly informs guideline updates, reshapes treatment algorithms, and accelerates adoption of emerging therapies across practice settings.

The momentum heading into ACC.26 follows a high-impact showing at ACC.25, where more than 50 late-breaking trials highlighted rapid advances across cardiometabolic care, lipid management, and interventional cardiology.

Notable data included the REVERSE-IT trial demonstrating rapid reversal of ticagrelor’s antiplatelet effects, the ALPACA study showing profound and sustained reductions in lipoprotein(a), and the ADVANCE-HTN trial evaluating novel approaches for treatment-resistant hypertension. These findings underscored a broader shift toward precision therapeutics, long-acting agents, and targeted mechanisms addressing previously unmet clinical needs.

Against this backdrop of accelerating innovation, ACC.26 is expected to build on these themes, with new data poised to further refine risk stratification, expand minimally invasive treatment strategies, and uncover novel drivers of cardiovascular disease. Increasingly, the field is moving toward earlier intervention and more individualized care, supported by advances in both pharmacologic and device-based therapies.

Presentation Title: Prevalence of Endogenous Hypercortisolism in Resistant Hypertension: Results of the MOMENTUM Trial
Presenter: Deepak L. Bhatt, MD, MPH, MBA
NCT06829537

MOMENTUM (NCT06829537), a prospective, multicenter observational study enrolling 1000 patients across 45 US sites, examines whether endogenous hypercortisolism (Cushing's syndrome) underlies treatment resistance in this population. Patients screening positive by dexamethasone suppression test (DST ≥1.8 µg/dL) undergo additional workup and adrenal imaging.

The design mirrors the CATALYST study, which found hypercortisolism in approximately 1 in 4 patients with difficult-to-control type 2 diabetes. Bhatt, a lead investigator and steering committee member, anticipates results will open new therapeutic pathways, potentially including cortisol-modulating agents, for patients whose hypertension remains poorly controlled on standard care.

2. HI-PEITHO (Boston Scientific / PERT Consortium)

Presentation Title: Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO): Primary Results
Presenter: Stavros Konstantinidis, MD, PhD
NCT04790370

HI-PEITHO is the first large-scale randomized controlled trial powered to determine whether ultrasound-facilitated, catheter-directed thrombolysis (USCDT) via the EKOS™ endovascular system plus anticoagulation improves outcomes versus anticoagulation alone in acute intermediate-high-risk pulmonary embolism (PE).

The 7-day primary composite endpoint includes PE-related death, cardiorespiratory decompensation or collapse, and non-fatal symptomatic PE recurrence. Enrolling 544 patients across 72 US and European hospitals, the adaptive-design trial addresses the longstanding gap left by the original PEITHO study, which demonstrated hemodynamic benefit of systemic thrombolysis at the cost of unacceptable hemorrhagic stroke rates. HI-PEITHO employs the validated National Early Warning Score (NEWS ≥9) to standardize decompensation criteria.

3. SURVIV Trial (Instituto Dante Pazzanese de Cardiologia, São Paulo)

Transcatheter Valve-in-Valve Versus Redo-Surgical Valve Replacement for Mitral Bioprosthetic Valve Dysfunction: Primary Results of the SURVIV Randomised Trial
Presenter: Dimytri A. Siqueira, MD, PhD

Bioprosthetic mitral valves inevitably undergo structural deterioration, yet the optimal reintervention strategy, transcatheter mitral valve-in-valve (mViV) via transseptal, balloon-expandable approach versus redo surgical mitral valve replacement (rMVR), has never been tested in a randomized trial.

SURVIV is a prospective, multicenter, open-label RCT enrolling 150 patients with mitral bioprosthetic valve dysfunction across multiple Brazilian centers, randomized 1:1 to mViV or rMVR. Bhatt, a co-investigator, noted the study could shift decision-making away from high-risk redo surgery toward a less invasive standard of care for this growing patient population, particularly as the prevalence of failed bioprostheses rises with longer patient lifespans and expanding valve repair programs.

4. IVUS-CHIP Trial (ECRI / Boston Scientific)

Presentation Title: Intravascular Ultrasound Guidance for Complex High-Risk Indicated Procedures: Primary Results of the IVUS-CHIP Trial
Presenter: Roberto Diletti, PhD
NCT04854070

Despite accumulating evidence favoring intravascular ultrasound (IVUS) guidance over angiography alone in PCI, rigorous randomized data in patients specifically defined as complex and high-risk, the CHIP population, have remained limited.

IVUS-CHIP is a randomized, controlled, multicenter, post-marketing study enrolling 2,020 patients with complex coronary lesions across approximately 40 hospitals in 7 European countries, randomized 1:1 to IVUS-guided versus angiography-guided PCI with a minimum 2-year follow-up. The primary endpoint is target-lesion failure, which is defined as a composite of cardiac death, target-vessel MI, and clinically indicated target-lesion revascularization.

Bhatt DL. Key clinical trial insights from ACC 2025, with Deepak Bhatt, MD, MPH, MBA. 

. Published April 9, 2025. Accessed March 20, 2026. 

https://www.hcplive.com/view/key-clinical-trial-insights-from-acc-2025-with-deepak-bhatt-md-mph-mba-

Corcept Therapeutics. Corcept Therapeutics initiates MOMENTUM trial to determine prevalence of hypercortisolism in patients with resistant hypertension. 

. Published March 10, 2025. Accessed March 19, 2026. 

https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-initiates-momentum-trial-determine/

Skhirtladze-Dworschak K, Konstantinidis SV, Rosenfeld K, et al. Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: rationale and design of the HI-PEITHO study. 

. 2026;S0002870326000013. doi:10.1016/j.ahj.2026.01.001. Accessed March 19, 2026.

Boston Scientific Corporation. The HI-PEITHO study. Boston Scientific website. Accessed March 19, 2026. 

https://www.bostonscientific.com/en-EU/medical-specialties/vascular-surgery/venous-thromboembolism-portal/pulmonary-embolism/clinical-data/hi-peitho.html

Siqueira DA, Abizaid AAC, Ramos AA, et al. Transcatheter valve-in-valve versus redo-surgical valve replacement for mitral bioprosthetic valve dysfunction: rationale and design of the SURVIV randomized trial. 

. Published online 2026. doi:10.4244/EIJ-D-25-01090. Accessed March 19, 2026.

Deepak Bhatt, MD, MPH, MBA, discusses 4 trials to watch at the upcoming ACC.26.

Deepak Bhatt, MD, MPH, MBA

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