Christian T. Ruff, MD, MPH is the Director of General Cardiology in the Cardiovascular Division at Brigham and Women's Hospital.

Christian T. Ruff, MD, MPH

The Future of Cardiology with Christian Ruff, MD, MPH

The rising star of the medical industry, 

 has seen progress over the last few years that most other specialties would not see for decades. From FDA approvals to improvements to diagnosis and treatment methods, the constant growth shows no signs of slowing.

These advancements have culminated in the 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

. Featuring over 4,750 abstracts and 1,300 expert faculty over 300 sessions, the Chicago conference covered 53 late-breaking clinical trials during its March 29-31 run.

A leading expert in the field, Christian T. Ruff, MD, MPH, Director of General Cardiology in the Cardiovascular Division at Brigham and Women's Hospital, sat down with 

's editorial team to discuss upcoming trials and his expectations for the rest of 2025.

: What are you looking forward to in cardiology for the rest of 2025?

Yeah, it's certainly exciting. There are so many incredible therapeutic areas. My takeaway from ACC, the thing I'm the most excited about outside of anticoagulation, which I care passionately about, is that I'm just blown away [by] the additional data for the GLP-1 receptor agonist. I mean, the ability of these drugs to modify kidney disease, heart failure, coronary atherosclerosis, peripheral vascular disease, and reduce weight. It's just a remarkable opportunity for us to improve the cardiometabolic health - health in general - of our population. And so I'm really excited about the data presented today [at ACC], and obviously at the upcoming conferences. It's just huge. I think enthusiasm for this field will really mark a paradigm shift in how we treat the global part of metabolic health of these patients. So I'm really excited about those classes of therapies.

Relevant disclosures for Ruff include Anthos Therapeutics, AstraZeneca, Bayer, Janssen, Novartis, and others.

Videos

Ruff discusses his expectations for cardiology for the rest of 2025, including new research into GLP-1 receptor agonists.

GLP-1 RAs and the Future of Cardiology, with Christian Ruff, MD, MPH

Abelacimab Cuts AF Bleeding Risk Across Ages with Christian Ruff, MD, MPH

Abelacimab, a novel factor XI inhibitor, significantly lowered the relative risk of bleeding, compared with rivaroxaban, across a spectrum of ages, with the ability for greater absolute reduction among individuals with 

This analysis of the AZALEA-TIMI 71 trial, presented at the 

, showed the absolute risk reduction (ARR) for patients ≥75 was 6.2% compared with 4.2% for those less than 75 years.

In an interview with HCPLive, Christian T Ruff, MD, MPH, TIMI Group senior investigator and director of general cardiology at Brigham and Women’s Hospital, pointed to the available data on undertreatment in patients with AF, particularly age as the ultimate indicator of frailty, medical comorbidities, and concern about bleeding.

“We’re talking about huge differences in bleeding and if you had a drug that was effective, that you could use without worry in patients who were 75–85, that would be a tremendous advance for clinicians and their patients,” Ruff told HCPLive. “If you ask why an elderly patient is not given an anticoagulant, it is often because they are old, frail, and clinicians are worried about bleeding. These results will be very encouraging to healthcare providers.”

AZALEA-TIMI 71 randomized 1287 patients with AF to abelacimab 90 mg or 150 mg monthly or rivaroxaban 20 mg or 15 mg daily across a median follow-up of nearly 2 years. This analysis used Cox proportional hazards to examine major and clinically relevant non-major bleeding by treatment age, older or younger than 75.

Nearly half (49%) of patients were ≥75 at baseline, with these patients reporting a lower body mass index (BMI) and a lower likelihood of being on antiplatelet therapy, but more likely to report creatine clearance ≤50 mL/min than younger patients (

Both abelacimab doses reduced the risk of major and clinically relevant non-major bleeding, irrespective of age, compared with rivaroxaban. Those above the age threshold had higher ARRs (7.1% and 6.2%) than those below 75 years (4.7% and 4.2%) in the 90 and 150 mg dose cohorts, respectively.

Notably, abelacimab reduced bleeding risk in patients ≥75, irrespective of renal function, BMI, and the use of concomitant antiplatelet therapy

“I think for the development program of abelacimab, the huge initial advance will be getting data in these populations who we're not treating at all, and they're at consequence for fatal strokes or permanent neurologic disability, loss of independence,” Ruff told HCPLive. “If we could deliver effective and safe therapy to those patients, that would be a remarkable achievement.”

Disclosures: Relevant disclosures for Ruff include Anthos Therapeutics, AstraZeneca, Bayer, Janssen, Novartis, and others.

Al Said S, Patel SM, Giugliano RP et al. Bleeding with the FXI Inhibitor Abelacimab Compared with Rivaroxaban in Older Individuals with Atrial Fibrillation: Analysis of the AZALEA-TIMI 71 Trial. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

Anthos Therapeutics shares new data from the landmark Azalea-TIMI 71 study demonstrating the factor XI inhibitor Abelacimab significantly reduced bleeding in patients regardless of age or bleeding risk. Anthos Therapeutics. March 29, 2025. Accessed March 31, 2025. 

https://anthostherapeutics.com/press-release/anthos_2025-03-29_release/

Ruff discusses a new analysis of AZALEA-TIMI 71 at ACC.25, which shows that the novel Factor XI inhibitor significantly lowered bleeding in elderly patients.

Christian T. Ruff, MD, MPH: Abelacimab Limits Bleeding Events in AZALEA–TIMI 71 Trial

Results from the Phase 2b AZALEA-TIMI 71 trial showed abelacimab, a novel factor XI inhibitor, achieved key reductions in bleeding events versus a standard-of-care direct-oral anticoagulant (DOAC) in patients with 

Announced by Anthos Therapeutics, Inc., and published in The New England Journal of Medicine, abelacimab 150 mg lowered major or clinically relevant non-major bleeding by 62%, compared with rivaroxaban 20 mg, in a population with AF at moderate-to-high risk of stroke.

“This is the largest and longest trial comparing a factor XI inhibition with a DOAC. I think this data is conclusive that factor XI inhibition with abelacimab in this trial is far safer than any anticoagulant strategy we have to date, and that would be a tremendous advance for a patient’s ability to be on and tolerate these medications,” Christian T. Ruff, MD, MPH, director of General Cardiology at Brigham and Women’s Hospital, and principal investigator of the AZALEA-TIMI 71 trial, told 

Estimates have suggested nearly half of patients with AF are not prescribed anticoagulants or are undertreated, with a primary barrier of bleeding risk concerns. Approximately 60 million people worldwide are impacted by AF, expected to increase by 60% by 2050 given the aging population.

AZALEA-TIMI 71, the longest head-to-head trial of a factor XI inhibitor, was halted early due to abelacimab’s favorable benefit-risk profile, particularly a greater-than-expected reduction in major and clinically relevant non-major bleeding. Once-monthly abelacimab 150 mg sustained a median 99% inhibition of Factor XI over 2 years.

The incidence of major or clinically relevant non-major bleeding was 3.2 events per 100 person-years with 150 mg abelacimab, compared with 8.4 events per 100 person-years with rivaroxaban (HR, 0.38; 95% CI, 0.24–0.60; 

 <.001). Compared with rivaroxaban, abelacimab 150 mg also achieved a 67% reduction in major bleeding alone (HR, 0.33; 95% CI, 0.16–0.66; 

 = .001) and an 89% reduction in gastrointestinal (GI) bleeding (HR, 0.11; 95% CI, 0.03–0.48).

A Phase 3 trial, LILAC-TIMI 76, was launched in January 2023 to determine the safety and efficacy of abelacimab on stroke reduction in AF, compared with placebo. Anthos announced their expectation for study completion by the second half of 2026.

“We believe this is an exciting opportunity if abelacimab demonstrates its efficacy in a Phase 3 trial, it would be a tremendous advance for our most vulnerable patients,” Ruff told 

. “That’s the next stage now that we’ve cemented the incredible safety profile of factor XI inhibition. Now, it’s time to demonstrate its efficacy for stroke reduction in a Phase 3 AF trial and we’re very excited that the trial is underway.”

Ruff CT, Patel SM, Giugliano RP, et al. Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation. N Engl J Med. 2025;392(4):361-371. doi:10.1056/NEJMoa2406674

Data published today in the New England Journal of Medicine demonstrates Anthos Therapeutics’ novel factor XI inhibitor, Abelacimab 150mg, reduced major or clinically relevant non-major bleeding by 62% compared to rivaroxaban (XARELTO) in patients with atrial fibrillation. Anthos Therapeutics. January 23, 2025. Accessed January 23, 2025. https://anthostherapeutics.com/press-release/anthos_2025-01-22_release/.

Soleimani H, Tavakoli K, Nasrollahizadeh A, et al. Estimating the burden of atrial fibrillation and atrial flutter with projection to 2050 in Iran. Sci Rep. 2024;14(1):20264. Published 2024 Aug 31. doi:10.1038/s41598-024-71296-4

Articles

The Phase 2b AZALEA-TIMI 71 trial demonstrated that abelacimab, a novel factor XI inhibitor, significantly reduced bleeding events compared to rivaroxaban in patients with atrial fibrillation (AF). Abelacimab 150 mg achieved a 62% reduction in major or clinically relevant non-major bleeding and a 67% reduction in major bleeding alone. The trial was halted early due to its favorable benefit-risk profile. A Phase 3 trial, LILAC-TIMI 76, is underway to assess abelacimab's efficacy in stroke reduction, with completion expected by 2026.

Abelacimab achieved notably lower levels of free factor XI and fewer bleeding events than standard-of-care rivaroxaban in the Phase 2b trial.

Christian T. Ruff, MD, MPH: Abelacimab Minimizes Bleeding Risk of Anticoagulants   

A new analysis of the AZALEA-TIMI 71 study showed abelacimab, a novel factor XI inhibitor, achieved consistent reductions in bleeding risk for patients on or off 

American Heart Association (AHA) Scientific Sessions 2024

, these findings on the effect of abelacimab may offer a potentially safer option for patients with 

 who experience an elevated bleeding risk with traditional anticoagulants.

“I think what a drug like abelacimab allows us to do is confidently be able to treat patients with the antithrombotic therapy that both maximizes their stroke potential from AF, but also protects them from coronary disease,” Christian T. Ruff, MD, MPH, senior investigator of the TIMI Group and director of general cardiology at Brigham and Women’s Hospital, told 

. “Even when you add an antiplatelet agent, so combination anti-thrombotic therapy, you don't see any increased risk of bleeding. That allows us to optimally manage not only our patient's AF but also their comorbidities.”

Abelacimab, a novel, investigational, highly selective, fully human monoclonal antibody, binds to factor XI to block activation and prevent the generation of the activated factor XIa form. AZALEA-TIMI 71, launched in February 2021, enrolled 1287 for a head-to-head comparison of the factor XI inhibitor to a standard-of-care anticoagulant.

Among the study population, 318 (25%) had already received antiplatelet therapy, including aspirin alone (16%), P2Y12 (7%), or dual antiplatelet therapy combining both (2%). Among the population, those treated with antiplatelet therapy had a higher rate of coronary artery disease (70% vs. 42%), previous heart attacks (36% vs. 16%), and peripheral artery disease (15% vs. 11%).

The prespecified analysis revealed a 67% reduction in bleeding for patients on antiplatelet therapy receiving abelacimab 150 mg, compared with rivaroxaban (incidence rate, 3.5% vs. 10.6%). Absolute bleeding rates were higher with the combination of rivaroxaban and antiplatelet therapy, compared with rivaroxaban alone (10.6% vs. 7.7%).

However, Ruff and colleagues noted the bleeding rates treated with abelacimab 150 mg were similar irrespective of antiplatelet therapy use (3.5% vs. 3.1%). Overall, the absolute risk difference between abelacimab 150 mg and rivaroxaban was greater in those on antiplatelet therapy, compared with those not receiving antiplatelet therapy (7.1% vs. 4.6%).

“The promise of factor XI inhibition was to deliver effective therapy to reduce thromboembolic events, but far safer,” Ruff told 

 “I think the AZALEA-TIMI 71 study cements the safety of factor XI inhibition, particularly with abelacimab, that this therapy is far safer than anything we've seen with an anticoagulant.”

Disclosures: Ruff reports no relevant disclosures.

Said SA, Patel SM, Giugliana R, Morrow DA, et al. Bleeding with the FXI Inhibitor Abelacimab compared with Rivaroxaban in Patients on Antiplatelet therapy: A Prespecified Analysis of the AZALEA-TIMI 71 Trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.

Abelacimab, a novel factor XI inhibitor, demonstrated significant reductions in bleeding risk compared to rivaroxaban in the AZALEA-TIMI 71 study, even for patients on antiplatelet therapy. This investigational monoclonal antibody offers a potentially safer anticoagulant option for atrial fibrillation patients, particularly those with elevated bleeding risks. The study showed a 67% reduction in bleeding for patients on antiplatelet therapy with abelacimab. The findings suggest that factor XI inhibition with abelacimab could provide effective thromboembolic event reduction with improved safety over traditional anticoagulants.

Christian. T. Ruff, MD, MPH describes an analysis of AZALEA-TIMI 71 demonstrating the substantial benefit of abelacimab on bleeding outcomes in patients on antiplatelet therapy.





 