Latest Evidence in Lipid Management

3,048 South Korean patientswith ASCVD (mean age 64.4 years; 20.9% women) across 17 sites, randomized to LDL-C targets of <55 vs <70 mg/dL using statins and ezetimibe. Target LDL was achieved in 60.8% (<55 group) and 68.1% (<70 group) at 3 years, with median LDL of 56 vs 66 mg/dL.

The rate of primary endpoint events was significantly lower with the stricter vs conventional LDL target (6.6% vs 9.75%; HR 0.67; 95% CI 0.52-0.86). Rates of both nonfatal MI (0.8% vs 1.7%; HR 0.46; 95% CI 0.23-0.91) and any revascularization (4.8% vs 7.5%; HR 0.63; 95% CI 0.47-0.84) were significantly lower with the <55 mg/dL target.

Lee YJ et al. (presented by Kim BK). N Engl J Med. 2026.

Individual patient-level meta-analysis of 19 randomized controlled trials encompassing 123,940 participants. Systematically evaluated 66 commonly reported statin side effects using blinded trial data to distinguish true drug effects from nocebo responses.

Of the 66 listed side effects, only 4 were confirmed as causally linked to statins: elevated liver transaminases, abnormal liver function tests, urinary changes, and peripheral edema. Critically, cognitive impairment, depression, neuropathy, and muscle pain were NOT caused by statins — findings that should help reduce statin non-adherence driven by nocebo-related concerns.

CTT Collaboration. Lancet. 2026.

7,062 post-MI patients randomized to colchicine 0.5 mg daily vs placebo within 72 hours of acute myocardial infarction. Primary endpoint: composite of cardiovascular death, recurrent MI, stroke, or ischemia-driven revascularization.

Colchicine vs placebo: 9.1% vs 9.3% (HR 0.99; 95% CI 0.85-1.16; P=0.93). CRP was significantly reduced with colchicine, but this did not translate into clinical benefit. These results contrast with the positive COLCOT and LoDoCo2 trials, suggesting that timing matters — anti-inflammatory therapy may benefit chronic stable CAD but not the acute MI setting.

Jolly SS et al. N Engl J Med. 2024.

12,257 patients (median age 66; 43% women) with atherosclerosis or diabetes but no prior MI or stroke, randomized to evolocumab 140 mg Q2W vs placebo over a median follow-up of 4.6 years. Evolocumab achieved median LDL of 45 mg/dL (55% reduction from baseline 122 mg/dL).

3-point MACE (CV death, MI, ischemic stroke): 6.2% vs 8.0%; HR 0.75; 95% CI 0.65-0.86; p<0.001. 4-point MACE (+revascularization): HR 0.81; 95% CI 0.73-0.89; p<0.001. MI alone: HR 0.64; 95% CI 0.52-0.79 (36% reduction). Revascularization: HR 0.79; 95% CI 0.70-0.88. All-cause mortality: 7.9% vs 9.7% (numerical reduction, not statistically significant per hierarchical testing). No new safety signals.

Bohula EA et al. N Engl J Med. 2026;394(2):117-127.

Prespecified subgroup analysis of VESALIUS-CV: 3,655 patients with high-risk type 2 diabetes (duration ≥10 years, daily insulin, or microvascular disease) without known significant atherosclerosis, no prior MI or stroke. Mean age 65; 57% women. Median follow-up 4.8 years. Evolocumab achieved LDL of 52 mg/dL at 48 weeks (vs 111 mg/dL placebo; baseline 121 mg/dL).

3-point MACE (CHD death, MI, ischemic stroke): 5.0% vs 7.1%; HR 0.69; 95% CI 0.52-0.91; p=0.009 (ARR 2.1%). 4-point MACE (+revascularization): 7.6% vs 10.5%; HR 0.69; 95% CI 0.55-0.86; p=0.009 (ARR 2.9%). CV death: 2.6% vs 4.0%; all-cause mortality: 7.8% vs 10.1% (both hypothesis-generating, not powered). No new safety signals. Larger relative benefit than the overall VESALIUS-CV trial (HR 0.69 vs 0.75).

Marston NA, Bohula EA, Bhatia AK, et al. JAMA. 2026.

FOURIER open-label extension analysis of 2,526 patients aged ≥75 years with established ASCVD, followed for a median of 7.1 years on evolocumab. Evaluated long-term efficacy and safety of PCSK9 inhibition in the elderly population where treatment decisions are often most uncertain.

Primary endpoint: HR 0.79 (95% CI 0.64-0.97). Absolute risk reduction of 5.4%, yielding NNT of 19 — substantially more favorable than the NNT of 44 observed in younger patients, reflecting higher baseline risk. No safety signals specific to the elderly population emerged over the extended follow-up period.

Al Said S et al. J Am Coll Cardiol. 2025.

FOURIER open-label extension analysis of 5,291 patients with prior ischemic stroke, followed for approximately 7 years on evolocumab. Specifically addressed the long-standing concern about whether very low LDL-C levels increase hemorrhagic stroke risk.

Patients achieving LDL <40 vs ≥70 mg/dL: IRR 0.69 (95% CI 0.57-0.84) for recurrent ischemic events. Crucially, no increase in hemorrhagic stroke (P=0.85) was observed even at very low LDL levels, providing long-term safety reassurance for aggressive lipid lowering in stroke patients.

Monguillon V et al. Circulation. 2025.

Phase 3 trial of 2,909 patients across 168 sites in 14 countries (mean age 63; 40% women). Daily 20 mg enlicitide achieved 57.1% LDL-C reduction at 24 weeks(vs 3.0% placebo; adjusted difference -55.8pp; p<0.001). At 52 weeks, LDL reduction sustained at -47.6% between-group difference.

Non-HDL-C: -53.4%. ApoB: -50.3%. Lp(a): -28.2% (all p<0.001). 70.3% reached LDL <70 mg/dL with ≥50% reduction(vs 1.5% placebo); 67.5% reached <55 mg/dL with ≥50% reduction (vs 1.2%). Adverse events similar between groups (64% vs 62%); discontinuation 3% vs 4%. If approved, enlicitide would be the first oral PCSK9 inhibitor.

Navar AM et al. N Engl J Med. 2026;394(6):529-539.

Phase 3 trial of 301 statin-treated adults with hypercholesterolemia randomized across 4 arms: enlicitide vs bempedoic acid vs ezetimibe vs ezetimibe + bempedoic acid combination. Primary endpoint: mean percent change in LDL-C at week 8.

Enlicitide LDL-C reduction: -64.6% from baseline at week 8. vs bempedoic acid: -56.7pp greater (95% CI -64.3 to -49.0; p<0.001). vs ezetimibe: -36.0pp greater (95% CI -41.8 to -30.2; p<0.001). vs combination: -28.1pp greater(95% CI -33.6 to -22.6; p<0.001).

ApoB -54.6%, non-HDL -58.0%, Lp(a) -26.2%. 78.2% achieved ≥50% LDL reduction AND LDL <55 mg/dL (vs 2-20% in comparator arms). No serious adverse events; 98% adherence across all arms.

Catapano AL et al. J Am Coll Cardiol. 2026.

2,530 patients with HeFH or ASCVD on maximally tolerated lipid-lowering therapy, randomized to obicetrapib 10 mg daily vs placebo. Primary endpoint: percent change in LDL-C at 84 days.

Obicetrapib 10 mg: LDL-C -29.9% vs +2.7% placebo (difference -32.6 percentage points; P<0.001). Exploratory cardiovascular outcomes: HR 0.79 for MACE (not powered for outcomes). Clean safety profile with no significant increase in adverse events. Obicetrapib revives the CETP inhibitor class after prior failures (torcetrapib, dalcetrapib) by selectively targeting LDL-C without off-target effects.

Nicholls SJ et al. N Engl J Med. 2025.

Phase 2 trial of 320 participants with Lp(a) ≥175 nmol/L, randomized to escalating doses of lepodisiran (a subcutaneous siRNA targeting hepatic apolipoprotein(a) synthesis) vs placebo over 1 year.

Lp(a) reductions: -40.8% (16 mg) to -93.9% (400 mg). At 1 year, 91% of patients on the 400 mg dose remained below their baseline Lp(a), supporting potential once-yearly dosing. Phase 3 cardiovascular outcomes trial (ACCLAIM-Lp(a)) is actively enrolling — the first study designed to determine whether lowering Lp(a) reduces heart attacks and strokes.

Nissen SE et al. N Engl J Med. 2025.

Phase 2 trial of 233 participants with Lp(a) ≥175 nmol/L, randomized to oral muvalaplin (which disrupts the apolipoprotein(a)-apolipoprotein B100 interaction needed to form Lp(a) particles) at doses ranging from 10 mg to 240 mg daily vs placebo.

Lp(a) reductions: 47.6% (10 mg) to 85.8% (240 mg). ApoB reductions up to 16.1%. As the first oral Lp(a) inhibitor, muvalaplin offers a fundamentally different route of administration compared to injectable siRNA and antisense approaches, potentially broadening patient access to Lp(a)-lowering therapy.

Nicholls SJ et al. JAMA. 2025.

354 patients with heterozygous familial hypercholesterolemia (HeFH) on maximally tolerated lipid-lowering therapy, randomized to obicetrapib 10 mg daily vs placebo. Addressed the persistent unmet need for additional LDL-lowering options in HeFH.

Obicetrapib achieved LDL-C reduction of -36.3% at day 84 and -41.5% at day 365. Additionally: ApoB -24.4%, Lp(a) -45.9%, and HDL-C +138.7%. The dual LDL-C and Lp(a) lowering makes obicetrapib uniquely suited for HeFH patients who frequently have elevated Lp(a) as a compounding risk factor.

Nicholls SJ et al. Nat Med. 2026.