The Next Act in Cardiovascular Medicine: Durable Drugs, Earlier Prevention, Smarter Delivery

Why cardiology is back in the spotlight

Cancer breakthroughs, rare-disease gene therapies, and the obesity drug boom have dominated the past decade of biopharma headlines. But while GLP-1s (obesity) and Rezdiffra (MASH) have captured Wall Street and mainstream attention, the biggest killer remains cardiovascular disease (CVD).

Quietly but forcefully, cardiology is entering its own innovation cycle. A new generation of therapies, spanning RNA, gene editing, enzyme inhibitors, and AI-guided prevention, promise to shift the field from reactive care to long-term risk management. The ESC Congress in Madrid, the World Congress of Cardiology, showcased a bevy of exciting new developments.

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From episodic care to annual prevention

Corsera Health, founded by industry veterans John Maraganore and Clive Meanwell, is emblematic of this pivot. The startup is developing once-yearly siRNA injections that simultaneously target LDL cholesterol (PCSK9) and blood pressure (angiotensinogen). Coupled with an AI tool called Klotho to forecast lifetime atherosclerotic risk, the model moves care upstream -- aiming to prevent CVD decades before the first event.

Commercially, Corsera is experimenting with a high-volume, low-margin strategy and even subscription-like distribution, a marked departure from traditional specialty-drug economics. If scalable manufacturing can deliver multi-ton oligo production, Corsera could be as much a population health platform as a biotech.

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Lipids: the most competitive sandbox in medicine

Few therapeutic areas are as dynamic right now as lipid management:

• Oral PCSK9 inhibitors: Merck’s enlicitide decanoate just delivered another Phase 3 win, positioning it to become the first oral entrant in a class dominated by injectables (Repatha, Praluent, inclisiran). A 14,500-patient outcomes trial is underway. AstraZeneca isn’t far behind with laroprovstat, already positive in Phase 2b. Orals could democratize PCSK9 therapy in ways antibodies never did.
• Gene editing: Editas Medicine has pivoted from ultra-rare diseases to LDL lowering with EDIT-401, editing the LDLR gene. Nonhuman primates showed ~90% cholesterol reduction; human data are expected in 2026. Lilly’s buyout of Verve underscores the belief that durable LDL reduction is a multibillion-dollar opportunity.
• RNAi for prevention: Beyond inclisiran, Corsera’s siRNA combo envisions yearly dosing that controls both LDL and blood pressure, potentially multiplying risk reduction across two primary drivers of atherosclerosis.

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Triglycerides: from rare disease to mainstream impact

Ionis’ Tryngolza, an apoC-III antisense therapy, achieved ~60 percentage-point placebo-adjusted triglyceride reductions in patients with moderate hypertriglyceridemia at six months, normalizing levels in up to 89% of treated patients. While initially approved only for familial chylomicronemia syndrome, the bigger commercial opportunity lies in broader hypertriglyceridemia, a condition touching millions and tied to both CVD and pancreatitis.

Pivotal readouts in severe hypertriglyceridemia (CORE and CORE2) are imminent. A clean safety profile and robust efficacy set the stage for label expansion and a potential blockbuster trajectory.

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Hypertension’s renaissance: targeting aldosterone synthesis

Despite dozens of antihypertensives, half of treated patients worldwide still miss target blood pressures. That reality may shift with aldosterone synthase inhibitors. AstraZeneca’s baxdrostat cut systolic blood pressure by ~9–10 mmHg (placebo-adjusted) at 12 weeks in resistant/uncontrolled patients and showed striking ~15 mmHg 24-hour ambulatory reductions. Safety (notably hyperkalemia) was manageable. The trial results drew spontaneous applause at the ESC Congress, with experts calling it a “game changer.” Rival lorundrostat from Mineralys is close behind.

The biology is compelling: aldosterone is a master regulator of salt, water, and vascular stiffness. Long-acting inhibitors could reset underlying disease trajectory rather than merely mask symptoms. With AZ targeting a 2025 filing, the commercial stakes are high following its $1.3B CinCor acquisition.

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Evidence for personalization: frailty and step-down therapy

Not every innovation involves a new molecule -- treatment strategy can be just as important. Sometimes it’s about knowing when not to de-intensify. The RETREAT-FRAIL trial in nursing home residents ≥80 years found no mortality or morbidity benefit from stepping down antihypertensives compared with usual care. Prior observational data had suggested otherwise. The trial reinforces a theme: in frail elders, therapy should be individualized, not reflexively simplified.

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Beyond function: remodeling standards in niche cardiology

Cytokinetics’ aficamten appeared to redefine expectations in obstructive hypertrophic cardiomyopathy (oHCM), outperforming the beta blocker metoprolol on exercise capacity and multiple secondary endpoints in the MAPLE-HCM study. With a December PDUFA date, aficamten could challenge beta blockers as first-line therapy in oHCM, despite cost hurdles. The lesson is broader: when drugs deliver functional superiority and quality-of-life gains, even entrenched generics can be displaced.

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Cholesterol risk in the young: a prevention wake-up call

A recent Danish cohort study highlights why these innovations matter for earlier intervention. Among nearly 24,000 adults with CAC scores of zero, elevated LDL was strongly associated with noncalcified plaque and higher future event risk, especially in those under 45. Each 1 mmol/L LDL increase raised the odds of noncalcified plaques by 21% overall, and 39% in younger adults, and boosted risk of myocardial infarction by 26%.

The message is stark: a “clean” calcium score in a 40-year-old doesn’t mean low risk if LDL remains uncontrolled. This evidence supports earlier LDL lowering, independent of CAC, and dovetails perfectly with the new generation of durable, preventive medicines.

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Commercial playbooks are evolving with the science

What ties these programs together are three thematic structural shifts:

1. Durability as value: Whether annual injections, one-time editing, or enzyme blockade, these drugs reduce the burden of daily adherence and could reshape lifetime care economics.
2. Volume over margin: Companies like Corsera are openly pursuing scalable, affordable models that mirror consumer health distribution rather than boutique specialty pricing.
3. Manufacturing as moat: Multi-ton oligo production and scalable gene-editing delivery will be competitive advantages as much as trial design or IP.

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The bottom line

Cardiology is no longer quietly ticking along in the background of oncology and obesity. It is in the midst of a renaissance, with new modalities poised to displace standards once thought immovable -- statins, beta blockers, multi-drug antihypertensive regimens. This isn’t just about lowering numbers on a lab report; it’s about reframing prevention decades earlier, extending "health-span," and bending the trajectory of the world’s leading killer.

For investors, the scientific community, investors and policymakers, the calculus is shifting. The portfolio of cardiology innovation now rivals oncology and metabolism for scientific excitement and commercial potential. And for patients, the prospect of once-yearly prevention, oral biologic substitutes, and risk-guided therapy from youth to old age marks nothing short of a new era in cardiovascular care.