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The next phase of cardiovascular innovation will be defined less by breakthrough molecules alone and more by how quickly new therapies move earlier into prevention, risk stratification, and durable patient management.
In a Harvard KOL Series discussion convened by Bank of America Global Research and Mass General Brigham, Calum MacRae MD PhD, Pradeep Natarajan MD, and Jorge Plutzky MD examined how emerging LDL-lowering therapies, Lp(a) programs, triglyceride-directed approaches, and next-generation risk models are reshaping the future of preventive cardiology.
A central theme was the shift toward earlier escalation and longer-duration prevention strategies, with less tolerance for statin limitations delaying the next therapeutic step.
That mindset reflects a broader move upstream, where prevention begins earlier, therapy duration extends longer, and precision risk models increasingly guide when intervention should start.
The genetic rationale for Lp(a) as a causal cardiovascular risk factor is as strong as it gets in pre-clinical evidence, according to Natarajan. Upcoming outcomes data from the Horizon trial with pelacarsen and Amgen’s OCEAN(a) trial with olpasiran are expected to determine whether Lp(a) lowering translates into meaningful clinical benefit at scale.
ACC and AHA guidelines now recommend universal Lp(a) screening. Investor consensus around a hazard ratio of 0.85 in the Horizon trial has raised questions about whether that level of benefit would support broad adoption, or whether use would be restricted to the highest-risk patients.
MacRae offered a more measured view, noting that demonstrating transmissibility of Lp(a) risk has proven surprisingly difficult for a Mendelian trait. He was the only clinician to leave open the possibility of a negative Horizon result, saying the devil will be in the actual outcomes data.
Prevention pathways are moving beyond statin-only frameworks toward faster escalation for high-risk patients. Updated ACC/AHA guidelines now include lower LDL targets and clearer guidance on primary prevention, a shift the clinicians described as long overdue.
Natarajan noted that European guidelines lowered targets in 2019 and that the updated U.S. guidelines largely formalize practices many cardiologists have already been following. The practical question now is whether primary care physicians will follow at scale.
PCSK9 inhibitors were clinically compelling but commercially underperformed due to a cluster of access, pricing, and launch execution failures. That history is directly shaping how clinicians and investors think about the next wave of therapies.
Plutzky noted that the threshold for oral acceptance among patients is lower, not because injectables are difficult, but because the average clinician does not convey their simplicity the way a specialist would. That communication gap, as much as the modality itself, may drive oral adoption.
Oral LDL-lowering agents, including oral enlicitide expected to receive approval this year, may reduce patient hesitation around injectables. Plutzky was direct: had pricing been lower at launch, PCSK9 inhibitors would have been widely used far earlier.
Imaging, triglyceride burden, family history, and prior cardiovascular events are becoming essential tools in matching patients to the right therapeutic pathway. Clinicians are increasingly using subclinical atherosclerosis imaging as an entry point for lipid-lowering therapy in primary prevention, a shift that could meaningfully expand the addressable population for newer agents.
For Lp(a) specifically, the clinicians expect trial results will drive a targeted rather than broad indication, most likely restricted to the highest-risk secondary prevention patients who mirror the enrollment criteria of the Horizon trial.
Cardiovascular innovation is no longer only about new science. It is about building clinical pathways, access models, and prevention frameworks that enable innovation to scale quickly and reach the patients who need it most.
The shift upstream, toward earlier intervention, longer prevention duration, and precision risk stratification, is redefining what success looks like for cardiovascular therapeutics. The commercial and clinical implications of that shift will be front and center at the 2026 World Medical Innovation Forum.
At the 2026 World Medical Innovation Forum
These are the strategic questions that will continue to shape cardiovascular discussions at the Forum, where healthcare leaders decide what scales next.
The 2026 Forum convenes the center of healthcare innovation — senior industry executives, top investors, leading Harvard clinicians and scientists, entrepreneurs, and government officials. Candid dialogue and collaborative innovation accelerate progress and improve patient care.
Presented in Boston by Mass General Brigham in collaboration with Bank of America, the 2026 Forum takes place September 22–23 at the Westin Boston Seaport District. The theme, Innovation at Speed and Scale, will spotlight the technologies and people creating the newest therapies and care enhancements.
Explore what’s next in cardiovascular medicine at the 2026 World Medical Innovation Forum.
Calum MacRae MD PhD
Vice Chair for Scientific Innovation, Department of Medicine, Brigham and Women’s Hospital
Professor of Medicine, Harvard Medical School
Pradeep Natarajan MD
Director of Preventive Cardiology and the Paul and Phyllis Fireman Endowed Chair in Vascular Medicine, Massachusetts General Hospital
Associate Professor of Medicine, Harvard Medical School
Associate Member, Broad Institute of Harvard and MIT
Jorge Plutzky MD
Director of Preventive Cardiology, Brigham and Women’s Hospital
Associate Professor of Medicine, Harvard Medical School
About This Series
This discussion is part of the Harvard KOL Series, a program convened by Bank of America Global Research and Mass General Brigham in advance of the World Medical Innovation Forum. Similar topics will be examined at the Forum in Boston, September 22-23, 2026.
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