# Metoprolol vs. Diltiazem in Patients with Angina and Non-Obstructive Coronary Artery Disease with or Without Evidence of Coronary Microvascular Spasm on Acetylcholine Testing

**Authors:** Angelo Giuseppe Marino, Nello Cambise, Fabio De Benedetto, Ludovica Lenci, Sara Pontecorvo, Federico Di Perna, Giacomo Buonamassa, Antonietta Belmusto, Saverio Tremamunno, Antonio De Vita, Rosangela Capasso, Rocco Antonio Montone, Gaetano Antonio Lanza

PMC · DOI: 10.3390/jcm14217635 · Journal of Clinical Medicine · 2025-10-28

## TL;DR

This study compared metoprolol and diltiazem in patients with angina and non-obstructive coronary artery disease, finding similar outcomes regardless of coronary microvascular spasm status.

## Contribution

The study provides new evidence on the comparable effectiveness of metoprolol and diltiazem in ANOCA patients with or without microvascular spasm.

## Key findings

- No significant differences in SAQ scores between metoprolol and diltiazem in the CMVS group.
- ECG-EST results were comparable with both drugs in both CMVS and NEG groups.
- Short-term symptomatic outcomes were similar regardless of treatment or spasm status.

## Abstract

Background: Pharmacologic therapy guided by invasive coronary function tests (CFTs) may improve symptomatic outcomes in patients with angina and non-obstructive coronary artery disease (ANOCA). In this study, we specifically aimed to investigate whether the induction of coronary microvascular spasm (CMVS) by the acetylcholine (Ach) test predicts a better therapeutic effect of calcium-channel blocker therapy compared to beta-blocker therapy. Methods: We enrolled 31 ANOCA patients, who were divided into two groups according to the result of Ach testing: 16 patients with CMVS (CMVS group) and 15 patients with a negative test (NEG group). Patients with Ach-induced epicardial spasm were excluded. In an open-label crossover trial, patients were randomly assigned to each receive, for a period of 4 weeks, either metoprolol (50 mg twice daily) or diltiazem (120 mg twice daily). At the end of each 4-week period, patients underwent an ECG–exercise stress test (EST) and were invited to fill out the Seattle Angina Questionnaire (SAQ). Results: No significant differences were found between metoprolol and diltiazem in terms of SAQ scores, and ECG-EST results were also largely comparable with the two drug treatments, both in the CMVS group and the NEG group. In particular, the SAQ summary score was 63.1 ± 24 and 66.0 ± 25 (p = 0.59) for metoprolol and diltiazem, respectively, in the CMVS group, and 70.9 ± 17 and 74.3 ± 16 (p = 0.37) with the two drugs, respectively, in the NEG group. Conclusions: Our small open-label study shows that patients with ANOCA with negative Ach test or Ach-induced CMVS show largely comparable short-term symptomatic outcomes and ECG-EST results when treated with either metoprolol or diltiazem.

## Linked entities

- **Chemicals:** metoprolol (PubChem CID 4171), diltiazem (PubChem CID 39186), acetylcholine (PubChem CID 187)
- **Diseases:** non-obstructive coronary artery disease (MONDO:0850371)

## Full-text entities

- **Diseases:** Angina (MESH:D000787), CMVS (MESH:D003329), epicardial spasm (MESH:D013035), ANOCA (MESH:D000088442)
- **Chemicals:** Metoprolol (MESH:D008790), Acetylcholine (MESH:D000109), Diltiazem (MESH:D004110)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12608405/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12608405/full.md

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Source: https://tomesphere.com/paper/PMC12608405