Multidomain lifestyle intervention in ANOCA: a sex-specific sub-analysis of the SAMCRO randomized controlled trial
S Caglioni, A Raisi, A Erriquez, M Cocco, A Cantone, J Farina, A Sarti, G Grazzi, R Pavasini, D Lazzeroni, F L Gurgoglione, G Niccoli, S Biscaglia, G CampoAbstract
Background
Angina with no obstructive coronary artery disease (ANOCA) significantly impairs quality of life in both sexes. While invasive diagnosis of coronary microvascular dysfunction or vasomotor disorder is essential for endotype tailored therapy, women often report higher symptom burden and worse quality of life at baseline. The Standardizing the Management of Patients with Coronary Microvascular Dysfunction (SAMCRO) trial recently showed that a multidomain lifestyle intervention improves outcomes beyond standard medical therapy; however, sex-specific responses to such integrated management remain underexplored.
Purpose
This sub-analysis of the SAMCRO trial evaluates whether sex influences clinical/endotype profiles in ANOCA and determines if the benefits of multidomain lifestyle intervention are consistent across sexes.
Methods
In the SAMCRO randomized trial, 123 patients with an invasive diagnosis of ANOCA were assigned 1:1 to a structured multidomain lifestyle intervention or guideline-directed standard care, stratified by sex, female (n=28 intervention vs n=28 control) and male (n=34 intervention vs n=33 control). The intervention integrated intensive cardiovascular risk-factor management, endotype-guided pharmacotherapy, supervised and home-based exercise training, dietary counselling, and psychological support. The primary endpoint was change in Seattle Angina Questionnaire (SAQ) summary score at 12 months.
Results
Baseline characteristics and endotype distribution were balanced across sexes, although women were older and less frequently smokers (Table 1). Compared to men, women exhibited higher baseline angina burden with lower SAQ summary score, a worse quality of life and more pronounced depressive symptoms (Table 1). Overall, treatment arms showed a balanced distribution of clinical features within each sex subgroup. At 12 months, SAQ summary score remained higher in men than in women; however, the multidomain intervention significantly improved health status in both sexes. The adjusted mean between-group difference was 7.10 points (95% CI, 0.87–13.30; p=0.026) in men and 17.60 points (95% CI, 11.87–23.20; p<0.001) in women (Figure 1). No significant treatment-by-sex interaction was observed (p-interaction=0.183), indicating consistent treatment effect across sexes.
Conclusion
Multidomain lifestyle intervention improves angina-related health status in ANOCA patients irrespective of sex. Although women presented with greater baseline symptom burden, treatment response was consistent across sexes, supporting a multidisciplinary management strategy, as recommended by current guidelines, for both men and women with invasively confirmed ANOCA.Table 1Figure 1