A familiar yet unresolved story further reinforced by data at the American College of Cardiology ( #ACC.26) scientific session is that of the injectable PCSK9 inhibitors. Late-breaking data for Repatha (evolocumab; Amgen) from the VESALIUS-CV trial demonstrated a ~31% reduction in major adverse cardiovascular events (MACE) in high-risk primary prevention patients with diabetes and without known significant atherosclerosis, with median follow-up of 4.8 years. Echoing Amgen’s SVP of R&D, “the evidence is unequivocal” and adds to the growing body of data showing intensive LDL-C lowering meaningfully reduces long-term cardiovascular risk.
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Despite this, uptake of PCSK9 inhibitors remains suboptimal. High cost, prior authorization requirements, and reimbursement headaches continue to limit access, even among high-risk populations who stand to benefit most. This disconnect between clinical efficacy and real-world utilization remains one of the most persistent challenges in lipid management; however, some constraints may be eased with emerging agents, such as oral formulations.
Merck presented late-breaking data from the CORALreef AddOn trial, showing LDL-C was reduced by 64.6% from baseline at eight weeks when its oral PCSK9 inhibitor, enlicitide decanoate, was added to background treatment with a statin, by 56.7% versus bempedoic acid, and by 28.1% vs bempedoic acid with ezetimibe. This provides evidence that PCSK9 inhibition may offer the greatest LDL-C lowering benefit compared to other long-standing generic medications, tied to reducing the long-term risk of MACE.
GLP-1 receptor agonists continue to increase their presence at cardiovascular congresses, with Eli Lilly and Novo Nordisk hosting two of the largest exhibits. New post-hoc data presented at #ACC.26 from SURPASS-CVOT reinforced their rapidly expanding role beyond glycemic control into CV risk reduction. Analyzing over 13,000 patients with diabetes and established CVD, Eli Lilly showed Mounjaro (dual GLP-1/GIP agonist tirzepatide) was associated with a significantly lower rate of major cardiorenal adverse events compared with Trulicity (GLP-1 agonist dulaglutide; Sanofi), marking a 16% relative risk reduction across outcomes such as all-cause mortality, myocardial infarction, and kidney events.
However, the continued excitement around the benefits GLP-1 RAs can deliver is confined by a familiar constraint: pricing. List prices for GLP-1s can still run over $1,000 per month, and coverage remains fragmented, limiting adoption. Medicare historically has not covered drugs used solely for obesity, Medicaid coverage varies by state, and many large employer plans continue to restrict coverage or require prior authorization, leaving many patients exposed to high out-of-pocket costs.
Hypertension, the “silent killer”, affects nearly 1 in 3 individuals worldwide, yet fewer than a quarter have it under control. Standard treatments, largely unchanged for decades, include ACE inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers, and diuretics. With aldosterone synthase inhibitors finally poised to enter the market this year, AstraZeneca in particular, had a significant marketing presence at #ACC.26 in preparation for its upcoming launch of baxdrostat versus Mineralys with lorundrostat, positioning them as the first meaningful innovation in hypertension in years.
Emerging approaches, including antisense oligonucleotides (ASOs) such as tonlamarsen (Kardigan), may offer an additional advantage by enabling less frequent dosing, which could help address one of the most persistent challenges in hypertension management: poor adherence to daily oral therapies. Early data at #ACC.26 from KARDINAL showed reductions in systolic blood pressure, although effects disappointingly appear more modest versus aldosterone synthase inhibitors. While Kardigan may now proceed with a more niche indication for tonlamarsen, notably absent from the congress was the much-anticipated Lp(a)HORIZON outcomes readout of IONIS/Novartis’ pelacarsen, now expected in mid-2026, which could further define the role of ASOs in large-scale cardiovascular indications, combatting adherence challenges.
This “last mile” problem reflects a complex interplay of factors: payer restrictions, administrative burden, and patient affordability. Even when therapies are guideline-recommended and produce undeniable favorable long-term outcomes, they often fail to reach eligible patients in a timely or equitable manner.
Ongoing policy initiatives, such as Medicare/Medicaid pricing pressure under Most Favored Nation (MFN) frameworks, new CMS pilot programs (BALANCE) for GLP-1 access, cash-pay and direct-to-patient pathways (AmgenNow, LillyDirect, NovoCare), and platforms such as TrumpRx.gov (advertising ~60% discounts for Repatha; 70-85% for GLP-1s) are all increasing pressure on the market to improve affordability.
ACC.26 has shown us cardiovascular innovation is alive and new therapies are providing meaningful, long-term outcomes. The ultimate impact of these treatment will hinge not just on clinical breakthroughs, but ensuring that therapies proven to reduce risk are delivered effectively and equitably.