Multidomain Rehabilitation for Older Patients with Myocardial Infarction (PIpELINe)

Authors, Journal, Affiliations, Type, DOI

• Tonet E, Raisi A, Zagnoni S, et al. for the PIpELINe Trial Investigators
• N Engl J Med 2025;393:973-82
• University Hospital of Ferrara (lead centre); 7 sites across Emilia–Romagna, Italy
• Randomized controlled trial (investigator-initiated, multicenter superiority)
• DOI: 10.1056/NEJMoa2502799; NCT04183465

Overview

The PIpELINe trial randomized 512 patients aged ≥65 (median 80 years) with impaired physical performance (SPPB score 4–9) one month after MI to a 12-month multidomain rehabilitation intervention (CV risk factor management, dietary counseling, and exercise training) vs. usual care in a 2:1 ratio. The primary composite of CV death or unplanned CV hospitalization at 1 year was reduced from 20.6% to 12.6% (HR 0.57, 95% CI 0.36–0.89, P=0.01), driven by an 8.5% absolute reduction in unplanned CV hospitalizations and a 5.6% absolute reduction in HF hospitalizations. There was no significant reduction in CV mortality alone (HR 0.69, NS). The intervention was safe with no serious adverse events and 71% overall compliance.

Keywords

Myocardial infarction, older adults, rehabilitation, physical performance, exercise training, frailty, SPPB, cardiac rehabilitation, secondary prevention, Otago Program

Key Takeaways

Background

• MI remains the leading cause of death and complications in older adults; this population has higher recurrence, rehospitalization, and death rates than younger adults
• Traditional cardiac rehabilitation has low participation, early withdrawal, and high costs — limitations even more pronounced in older/frail patients
• Older adults post-MI are the least physically active group, leading to accelerated physical decline, disability, and loss of independence
• Aerobic capacity declines >20% per decade after age 70 (Fleg 2005 Circulation)
• Home-based CR studies had a mean patient age of approximately 68 years; PIpELINe addresses a meaningfully older population (median 80 years)

Methods

• Multicenter, investigator-initiated, randomized superiority trial; 7 Italian sites (Emilia-Romagna region); March 2020 – November 2023
• Eligibility: age ≥65; STEMI or NSTEMI; successful coronary revascularization; SPPB score 4–9 at the 1-month post-discharge visit; preserved cognitive function
• SPPB (Short Physical Performance Battery): Score 0–12; three tests — standing balance, 4-m gait speed, 5-chair rise; lower score = greater impairment; 4–9 identifies "impaired but not maximally compromised" — neither too fit (limited ceiling) nor too compromised (intervention may be futile)
• Randomization 2:1 (342 intervention, 170 control); stratified by centre, sex, clinical presentation, SPPB score
• Intervention (3 components delivered over 12 months):
  1. CV risk factor management (smoking, BP, lipids, blood glucose) supervised at each visit per guidelines
  2. Nutritional assessment at inclusion + tailored diet plan
  3. Exercise training: 6 on-site supervised individual sessions (days 30, 60, 90, 180, 270, 360) + individualized home-based prescription; Otago Program (balance + upper/lower-limb functional strength); ≥20 min moderate walking ≥4×/week; intensity based on 1-km treadmill test; individualized progression per session
• Control: single in-person visit at 1 month; 30-min counseling with educational materials (diet, smoking, physical activity); guideline-based medications in both groups
• Primary outcome: composite of CV death or unplanned hospitalization for cardiovascular causes within 1 year
• Secondary outcomes: individual primary components; all-cause death; unplanned HF hospitalization; MI; revascularization; stroke; BARC 3/4/5 bleeding; SPPB; 10-m gait speed; hand-grip strength; EQ-5D-5L quality of life
• Statistical analysis: intention-to-treat; Fine–Gray subdistribution hazard models accounting for competing risks

Results

• 512 patients randomized; median age 80 years (IQR 75–84); 36% women; 68% frail or prefrail by Fried's criteria
• 37% STEMI, 63% NSTEMI; 64% multivessel disease; 93% complete revascularization
• 1-year follow-up complete for all 512 patients
• Primary outcome (CV death or unplanned CV hospitalization): 12.6% vs 20.6% (HR 0.57, 95% CI 0.36–0.89, P=0.01); absolute risk reduction ~8%; NNT ≈12.5
• CV death: 4.1% vs 5.9% (HR 0.69, 95% CI 0.31–1.55; NS)
• Unplanned CV hospitalization: 9.1% vs 17.6% (HR 0.48, 95% CI 0.29–0.79)
• Unplanned HF hospitalization: 1.5% vs 7.1% (HR 0.20, 95% CI 0.07–0.56)
• Subgroup consistency (benefit present): both sexes; diabetics (HR 0.32); CKD eGFR <60 (HR 0.36); LVEF ≤40% (HR 0.26); SPPB 4–6 (HR 0.39); gait speed below median (HR 0.49); high ARC bleeding risk (HR 0.51); prefrail (HR 0.48); NSTEMI (HR 0.55)
• Subgroups with attenuated/no benefit: peripheral artery disease (HR 1.06); low ARC bleeding risk (HR 0.93); not-frail (HR 0.79); gait speed at/above median (HR 1.02)
• No serious adverse events during supervised training sessions
• Compliance: 71% overall; 75% after excluding patients who died before completing; 19 patients died before completion; 81 permanently discontinued

Discussion

• PIpELINe shifts focus to the post-discharge period, integrating coronary revascularization with holistic, multicomponent rehabilitation in older patients
• SPPB 4–9 deliberately targets those neither too fit (limited improvement ceiling) nor too compromised (intervention likely futile) — the actionable rehabilitation zone
• HF hospitalization reduction (HR 0.20) is consistent with results of the REHAB-HF trial (Kitzman 2021 NEJM) in older acute HF patients
• Goals of care for older adults extend beyond survival: well-being, functional independence, autonomy, and quality relationships are independently important outcomes
• Socioeconomic implications of HF hospitalization reduction are significant given rising HF costs in older adults (Kazi 2024 Circulation)
• The intervention was early (started at 1 month), tailored, long-term (12 months), and limited in supervised sessions (6 total), enabling home-based adherence

Limitations of the Document

• Enrolled at 1 month post-MI: only 1-month survivors eligible; findings not generalizable to those dying within the first month
• Performance bias: patients unavoidably aware of treatment allocation
• Home-based activities not monitored; contribution of home vs. supervised components cannot be quantified
• Multicomponent intervention: impossible to isolate which component (risk factors, diet, exercise) drove the benefit
• Cognitively intact patients only: applicability to cognitive impairment unknown
• No longer-term follow-up to confirm durability beyond 1 year
• 29% permanently discontinued intervention (excluding deaths); need for alternative strategies for non-adherers
• Single Italian region (Emilia-Romagna): regional healthcare system factors may limit generalizability

Key Concepts Mentioned

• concepts/Cardiac-Rehabilitation — multidomain model for elderly/frail post-MI; PIpELINe as the primary RCT evidence base for this population
• entities/Frailty-in-Cardiovascular-Disease — SPPB as frailty/physical function measure; Fried's frailty criteria applied for characterization

Key Entities Mentioned

• entities/Acute-Coronary-Syndrome — post-MI secondary prevention context; multidomain rehab as complement to standard ACS secondary prevention
• entities/Heart-Failure — unplanned HF hospitalization as key secondary outcome; consistency with REHAB-HF (Kitzman 2021)
• entities/Peripheral-Artery-Disease — PAD subgroup showed no benefit from rehabilitation (HR 1.06)

Wiki Pages Updated

• wiki/sources/pipeline-mi-nejm-2025.md — created
• wiki/concepts/Cardiac-Rehabilitation.md — new older-patients/multidomain section; updated contradictions; source_count 1→2
• wiki/entities/Frailty-in-Cardiovascular-Disease.md — created
• wiki/entities/Acute-Coronary-Syndrome.md — elderly multidomain rehab note added; source_count 4→5
• wiki/wikiindex.md — Frailty-in-Cardiovascular-Disease entry added
• wiki/sourceindex.md — pipeline-mi-nejm-2025 entry added
• log.md — updated