NEJM This Week — June 11, 2026

This week's headline read is a practical anticoagulation-reversal review (the high-yield item below). The issue's two randomized trials both test IVUS vs. angiography guidance for PCI (complex lesions and left main) — both negative — summarized in PICO for awareness but flagged lower-yield for general practice. A teaching case and several non-randomized studies round out the issue.

Hematology / Critical CareReview · High yield · IM/ID

Antidotes for Anticoagulation Reversal

The week's most clinically actionable read. Key points:

•Factor Xa inhibitors (apixaban, rivaroxaban): per this review, andexanet alfa was withdrawn from the US market (Dec 2025); off-label 4F-PCC (25–50 IU/kg) is now the preferred reversal for life-threatening bleeding in the US. (Andexanet keeps conditional EMA approval in Europe, apixaban/rivaroxaban only.) •Dabigatran: idarucizumab 5 g IV; watch for delayed rebound (~20% at 24 h, especially in renal impairment) — recheck dTT/ECT. •Warfarin (VKA): 4F-PCC + IV vitamin K is preferred over FFP (faster INR correction, fewer transfusions). •No approved antidote for LMWH, fondaparinux, or danaparoid; protamine only partially neutralizes LMWH and is ineffective for fondaparinux. •Where andexanet is still used, do not combine it with PCC; ANNEXA-I showed better hemostasis but nearly doubled thrombosis (10.3% vs 5.6%).

CardiologyIVUS-CHIP · RCTLower yield · IM/ID

Intravascular Ultrasound–Guided or Angiography-Guided Complex High-Risk PCI

Population: 2,020 adults undergoing complex high-risk PCI — NSTE-ACS or stable ischemic heart disease with ≥1 complex lesion (severe calcification, ostial, true bifurcation, left main, chronic total occlusion, in-stent restenosis, or >28 mm) or planned mechanical circulatory support. Excluded: STEMI, cardiogenic shock, bypass-graft PCI, contrast/DAPT contraindication. Mean age 69; 79% men; 27% ACS; mean SYNTAX 25.
Intervention: IVUS-guided PCI using prespecified stent-optimization criteria (everolimus-eluting stents).
Comparison: Angiography-guided PCI (IVUS prohibited unless medically mandated).
Outcome: Target-vessel failure (cardiac death, target-vessel MI, or clinically-indicated target-vessel revascularization) at median 19 mo: 13.9% vs 11.1% (HR 1.25; 95% CI 0.97–1.60; P=0.08) — superiority not met. Notable secondary: definite stent thrombosis lower with IVUS (0.2% vs 1.0%; HR 0.20).

Clinical takeaway. Routine IVUS did not reduce target-vessel failure versus angiography in complex high-risk PCI; the one signal favoring IVUS was less definite stent thrombosis. Control-group event rates were lower than assumed (PCI standards have improved), and the result aligns with the Western ILUMIEN IV (OCT) trial. The editorial (Kastrati, "IVUS — A Zigzag Path to Success") frames intracoronary imaging as still mechanistically valuable for stent expansion/apposition even when major ischemic outcomes don't differ. Open-label; industry-funded (Boston Scientific).

CardiologyOPTIMAL · RCTLower yield · IM/ID

IVUS-Guided versus Angiography-Guided PCI in Unprotected Left Main Coronary Disease

Population: 806 adults with unprotected left main disease (≥50% stenosis) suitable for PCI, with moderate/severe ischemia or symptoms despite medical therapy; prior CABG allowed if no patent graft to the LAD/circumflex. Excluded: STEMI <48 h, cardiogenic shock, life expectancy <2 yr, DAPT/stent contraindication. Mean age 71; 78% men; 35% diabetes; mean SYNTAX 30.
Intervention: IVUS-guided PCI (mandatory post-stent IVUS with target lumen-area criteria).
Comparison: Angiography-guided PCI.
Outcome: Patient-oriented composite (any stroke, MI, revascularization, or all-cause death) at median 2.9 yr: 33.7% vs 30.9% (HR 1.11; 95% CI 0.87–1.42; P=0.40) — no benefit. Notable: stroke higher with IVUS (3.0% vs 1.0%; HR 3.11; 95% CI 1.00–9.65), called unexplained and possibly chance; stent thrombosis low and similar.

Clinical takeaway. Among IVUS-expert operators at high-volume European centers, IVUS guidance showed no outcome benefit over angiography in unprotected left main PCI. With IVUS-CHIP, two negative trials this week; the editorial (Welt, "Seeing the Left Main Coronary Artery Clearly — Is IVUS Always Necessary?") suggests these data may challenge a blanket class IA "always image" mandate for left main PCI when done by experienced operators. The excess stroke with IVUS is unexplained and likely chance. Open-label.

Teaching Case · Case Records of the MGH

Case 16-2026: A 14-Year-Old Girl with Hypertension · Rheumatology / Nephrology

Lower yield · IM/ID · pediatric, rare

Key learning point. Final diagnosis: Takayasu arteritis. A carotid bruit, elevated inflammatory markers, and renal-artery stenosis in an adolescent should prompt workup for large-vessel vasculitis. The renal-artery stenosis drives secondary aldosteronism — elevated renin and aldosterone with a low aldosterone-to-renin ratio (the discriminator from primary aldosteronism). Management pearl: avoid ACEi/ARB in bilateral or severe renal-artery stenosis; treat hypertensive emergency with IV nicardipine, then a calcium-channel blocker plus beta-blocker.

Also in this issue (not randomized, so not summarized as trials): Exa-cel in children (5–11 yr) with transfusion-dependent β-thalassemia or sickle cell disease — phase 3, open-label, single-group (CRISPR gene editing). IL-10 autoantibodies and HLA-DRB1*01:03 in IBD — observational seroprevalence/genetic-association study. Subretinal gene therapy for X-linked retinoschisis — single-group phase 1/2 in boys with a rare retinal disease.

Summaries are original paraphrases prepared for educational use; figures are drawn from the published full text. Read the full articles at NEJM.org (subscription required). Trial registrations: IVUS-CHIP (NCT04854070), OPTIMAL (NCT04111770). Citations: N Engl J Med 2026; Vol. 394, No. 22. DOIs: 10.1056/NEJMra2506021, 10.1056/NEJMoa2601521, 10.1056/NEJMoa2600440, 10.1056/NEJMcpc2517866.