Cardiology · Medical Literature
A Multidomain Lifestyle Intervention for Invasively Confirmed ANOCA: The SAMCRO Randomized Trial.
Abstract
Angina with no obstructive coronary artery disease (ANOCA) is associated with persistent symptoms and impaired quality of life. Although guidelines advocate a patient-centered, multidisciplinary approach, randomized evidence is lacking. The aim of this study was to determine whether a multidomain lifestyle intervention improves patient-reported health status and quality of life in patients with ANOCA. SAMCRO was a prospective, multicenter, randomized trial with blinded endpoint assessment. Patients with angina and invasive evidence of coronary microvascular dysfunction and/or coronary vasomotor disorder were randomized 1:1 to endotype-guided therapy plus a structured multidomain lifestyle intervention (intervention group) or endotype-guided therapy alone (control group). The intervention integrated exercise training, Mediterranean dietary counseling, and psychological support. The primary endpoint was the change in Seattle Angina Questionnaire summary score. A total of 123 patients were randomized (62 to intervention and 61 to control), with follow-up completed at 12 months for the primary endpoint. The mean age was 65.8 ± 9 years, and 46% were women. The adjusted mean improvement in Seattle Angina Questionnaire summary score was significantly greater in the intervention group (between-group difference: 13.12 points; 95% CI: 9.68-16.56; P < 0.001). A clinically meaningful improvement (≥10-point increase) was achieved in 48 (77%) versus 23 (38%) of patients, respectively (adjusted risk ratio: 1.98; 95% CI: 1.20-3.26; P < 0.001). Significant improvements were also observed in the EuroQol 5-Dimension 5-Level index and Beck Depression Inventory scores. In patients with invasively confirmed ANOCA, a structured multidomain lifestyle intervention provided clinically meaningful improvements in patient-reported health status on top of endotype-guided medical therapy. (Standardizing the Management of Patients With Coronary Microvascular Dysfunction [SAMCRO]; NCT06025994).
Clinical relevance
ANOCA (angina with no obstructive coronary artery disease), encompassing coronary microvascular dysfunction and vasomotor disorders, represents a clinically underserved population burdened by persistent angina and impaired quality of life despite the absence of obstructive disease. Current guidelines recommend a patient-centered, multidisciplinary approach, yet robust randomized controlled trial evidence to guide non-pharmacological management has been lacking. The SAMCRO trial directly addresses this evidence gap in a population that is frequently undertreated and underrepresented in cardiovascular intervention trials.
Key findings
1. In 123 patients with invasively confirmed ANOCA randomized 1:1, the adjusted between-group difference in Seattle Angina Questionnaire (SAQ) summary score at 12 months was 13.12 points (95% CI: 9.68–16.56; P < 0.001), favoring the multidomain lifestyle intervention arm over endotype-guided therapy alone. 2. A clinically meaningful response (≥10-point improvement in SAQ summary score) was achieved in 77% of intervention patients versus 38% of controls (adjusted risk ratio: 1.98; 95% CI: 1.20–3.26; P < 0.001), yielding an NNT of approximately 2.6. 3. Significant improvements in generic health-related quality of life were observed, as reflected by between-group differences in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) index score, favoring the intervention group. 4. Statistically significant improvements in Beck Depression Inventory (BDI) scores were demonstrated in the intervention arm, highlighting a measurable psychological benefit of the structured program. 5. The study population had a mean age of 65.8 ± 9 years with 46% women, reflecting the typical demographic of ANOCA — an older, near-majority female cohort with high symptom burden. 6. The intervention was structured and multimodal, integrating supervised exercise training, Mediterranean dietary counseling, and psychological support on top of endotype-guided pharmacotherapy, and was evaluated in a prospective, multicenter, blinded-endpoint-assessment design over 12 months.
Practice implications
For patients with angina in whom invasive functional testing confirms coronary microvascular dysfunction and/or vasomotor disorder, clinicians should consider prescribing a structured multidomain lifestyle program — encompassing exercise rehabilitation, Mediterranean diet counseling, and psychological support — as an adjunct to endotype-guided pharmacotherapy, given a number needed to treat of approximately 3 to achieve a clinically meaningful symptom benefit. Patient selection should prioritize those with documented invasive ANOCA diagnoses rather than presumptive cases, as the trial required objective endotyping via coronary function testing. The co-occurrence of depressive symptoms, which also improved significantly, underscores the importance of integrated psychological screening and support as a routine component of ANOCA management rather than an ancillary consideration.