Invasive Treatment Strategy for Older Patients with Myocardial Infarction

Authors, Journal, Affiliations, Type, DOI

• Authors: Vijay Kunadian, Helen Mossop, Carol Shields, Michelle Bardgett, et al.; British Heart Foundation SENIOR-RITA Trial Team and Investigators
• Journal: New England Journal of Medicine, 2024;391:1673–84
• Affiliations: Newcastle University / Newcastle upon Tyne Hospitals NHS Foundation Trust (PI); 48 NHS Trusts across England and Scotland
• Type: Prospective, multicenter, open-label, randomized controlled trial
• DOI: 10.1056/NEJMoa2407791
• Funding: British Heart Foundation (grant CS15/7/31679)

Overview

SENIOR-RITA is the largest RCT to date evaluating an invasive versus conservative strategy in elderly NSTEMI patients, enrolling 1,518 patients aged ≥75 years (mean age 82, 45% women, 32% frail) at 48 UK centres with a median follow-up of 4.1 years. The invasive strategy (coronary angiography ± revascularisation + best medical therapy) did not result in a significantly lower risk of the primary composite outcome (cardiovascular death or nonfatal MI: HR 0.94; 95% CI 0.77–1.14; P=0.53) compared with conservative management (best medical therapy alone). Nonfatal MI was reduced (HR 0.75; 95% CI 0.57–0.99), but numerically offset by more cardiovascular deaths (15.8% vs 14.2%). The radial approach was used in 89.3% and procedural complications were <1%, demonstrating that contemporary invasive care is safe even in frail elderly patients.

Keywords

NSTEMI, older adults, invasive strategy, conservative strategy, revascularisation, frailty, Fried Frailty Index, Rockwood Clinical Frailty Scale, myocardial infarction, cardiovascular death, radial access

Key Takeaways

Background and Rationale

• Specific guidelines for pharmacological and invasive treatment in older patients with ACS are lacking owing to underrepresentation of this population in clinical trials
• NSTEMI is the main ACS subtype in adults >75 years; frailty, cognitive impairment, and multimorbidity are prevalent in this population and historically served as barriers to invasive management
• At the time of design, only six small RCTs had investigated invasive strategy in elderly NSTEMI; results were inconsistent and sample sizes too small to be definitive

Trial Design

• Multicenter, open-label, randomised 1:1; invasive strategy (coronary angiography ± revascularisation within 3–7 days + best available medical therapy) vs conservative strategy (best medical therapy alone; angiography permitted for clinical deterioration)
• Stratification by site and Rockwood Clinical Frailty Scale score (frail ≥5 vs non-frail)
• Best available medical therapy: aspirin 75 mg, P2Y₁₂ antagonist, statin, beta-blocker (target HR 60–70 bpm), ACEi/ARB; guideline-directed management of hypertension, diabetes, hypercholesterolaemia
• Frailty assessed by Fried Frailty Index (frail ≥3 criteria) AND modified Rockwood Clinical Frailty Scale (frail ≥5); comorbidity by age-adjusted Charlson Comorbidity Index; cognitive function by MoCA

Patient Population

• 1,518 randomised (753 invasive; 765 conservative) from November 2016 – March 2023
• Mean age 82 years; 44.7% women; 32.4% frail (Fried); median Charlson Comorbidity Index 5; median MoCA 24 (62.5% had cognitive impairment, MoCA <26)
• Median randomisation time 2 days from hospitalisation
• Among screened-but-not-randomised patients: mean age also 82 years; 47% women — confirms broad representativeness

Invasive Treatment Details

• 90.3% of invasive-arm patients underwent coronary angiography; radial access in 89.3%
• Median time to angiography: 5 days from admission, 3 days from randomisation
• 49.9% underwent revascularisation: PCI in 46.6% (multivessel PCI 29.9%; balloon angioplasty only 4.9%), CABG in 3.3%
• Procedural complications <1%

Primary Outcome

• Cardiovascular death or nonfatal MI: invasive 25.6% vs conservative 26.3%; HR 0.94 (95% CI 0.77–1.14; P=0.53) — not significant
• At 1 year: 12.8% vs 16.8% (invasive favoured early); by 5 years: 35.4% vs 34.8% (curves converged) — proportional-hazards assumption violated; time-varying benefit
• Restricted mean event-free time: +29 days (95% CI −40 to 98) over 5 years — consistent with early benefit that erodes

Components of Primary Outcome

• Cardiovascular death: 15.8% vs 14.2%; HR 1.11 (95% CI 0.86–1.44) — numerically more in invasive arm
• Nonfatal MI: 11.7% vs 15.0%; HR 0.75 (95% CI 0.57–0.99) — nominally significant MI reduction

Secondary Outcomes

• All-cause death or nonfatal MI: 42.4% vs 42.0%; HR 0.97 (NS)
• Total MI (fatal + nonfatal): 13.3% vs 16.2%; HR 0.79 (95% CI 0.61–1.02; NS)
• Subsequent angiography: 5.6% vs 24.2%; HR 0.20 (95% CI 0.14–0.28) — markedly reduced in invasive arm
• Subsequent revascularisation: 3.9% vs 13.7%; HR 0.26 (95% CI 0.17–0.39) — markedly reduced
• TIA: 2.4% vs 1.2%; HR 2.05 (95% CI 0.92–4.56) — numerically higher invasive (NS)
• Bleeding: 8.2% vs 6.4%; HR 1.28 (95% CI 0.88–1.86) — numerically higher invasive (NS)
• Other secondary endpoints (stroke, death from any cause, HF hospitalisation) similar between groups

Subgroup Analyses

• Primary outcome findings generally consistent across all prespecified subgroups, including frail patients, patients with high comorbidity burden, and cognitively impaired patients

Limitations of the Document

• Recruited 1,518 vs planned 1,668 patients; COVID-19 pandemic hampered recruitment, especially frail/multimorbid patients; underpowered relative to original design
• Open-label design (unavoidable given invasive vs conservative assignment)
• Conservative arm had 24.2% subsequent angiography — some contamination/crossover; dilutes treatment comparison
• No formal quality-of-life outcome reported (not a secondary endpoint in this trial)
• 49.9% revascularisation rate in invasive arm: half of angiographied patients received no PCI/CABG, potentially explaining neutral primary result
• Competing non-cardiovascular mortality in a multimorbid elderly population may obscure any CV benefit

Key Concepts Mentioned

• concepts/NSTEMI-Elderly-Invasive-Strategy — primary concept for elderly NSTEMI invasive vs conservative management
• concepts/Frailty-Assessment-Tools — Fried Frailty Index and Rockwood Scale used in SENIOR-RITA

Key Entities Mentioned

• entities/Acute-Coronary-Syndrome — SENIOR-RITA provides trial data for elderly NSTEMI invasive strategy
• entities/Frailty-in-Cardiovascular-Disease — 32% frail population enrolled; safety and efficacy data in frail patients

Wiki Pages Updated

• Created wiki/sources/PCI-Elderly-SENIORRITA-NEJM-2024.md
• Created wiki/concepts/NSTEMI-Elderly-Invasive-Strategy.md
• Updated wiki/entities/Acute-Coronary-Syndrome.md
• Updated wiki/entities/Frailty-in-Cardiovascular-Disease.md
• Updated wiki/sourceindex.md
• Updated wiki/wikiindex.md