EDIT-CMD trial results: edifying our approach to patients with ANOCA
Reported from ACC 2022
Dejan Milasinovic provides his take on the EDIT-CMD Randomized Clinical Trial which aimed to assess the efficacy of diltiazem to improve coronary vasomotor dysfunction in angina and nonobstructive coronary arteries.
In the EDIT-CMD trial, 85 patients with angina but no obstructive epicardial disease (ANOCA) and with confirmed vasomotor and/or microvascular dysfunction were randomized to diltiazem or placebo. At baseline, all patients had undergone invasive CFR and IMR measurements, as well as acetylcholine test. Coronary microvascular dysfunction (CMD) was diagnosed in case of CFR≤2 and IMR≥25, and coronary spasm on angiography had to be paired with ECG changes and angina symptoms after incremental intracoronary acetylcholine administration.
The primary endpoint was the rate of normalization of functional parameters (CFR, IMR and spasm) on repeat testing after 6 weeks, which was not improved with diltiazem as compared with placebo. Over the 6-week period, 29% of patients improved in the placebo arm vs. 21% of those on diltiazem (p=0.46). In addition, diltiazem did not have an impact on angina and quality of life different than placebo.
Despite it being neutral, the randomized EDIT-CMD trial does seem to provide important insights in several respects and thus edify our approach to patients with ANOCA.
First, the presented results seem to reinforce the notion that ANOCA patients may most effectively be treated according to specific endotypes. Namely, whereas diltiazem failed to improve functional parameters of microcirculatory dysfunction, it did significantly reduce the burden of epicardial spasm (in 47% of patients vs. 6% in the placebo group, p=0.006). Given that in the group of patients treated with diltiazem 52% did not have epicardial spasm, and 54% had CMD (i.e. CFR≤2 and/or IMR≥25) in combination with epicardial spasm or alone, it may be conceivable that in such a mixed population the efficacy of diltiazem to reduce epicardial spasm and related angina may have been diluted.
Second, changes in the assessed coronary functional indices over time portray a dynamic picture of patients with ANOCA. In the placebo arm, functional improvement was registered in a third of patients and almost half of patients reported improvements in angina, comparable to patients receiving diltiazem. This may testify to the ability of the background therapy (≈30% beta-blockers and ≈40% ACE inhibitors) and lifestyle changes to confer benefit in ANOCA patients over the closely monitored study period.
In addition, biological variability of the coronary function over time may also play a role that needs to be investigated in the future. This aspect may be important given that close to 90% of patients reported anginal symptoms at rest, which improved over the course of the study even in the placebo group.
Overall, the EDIT-CMD trial showed that using diltiazem in a mixed-endotype population of patients with ANOCA may not be beneficial in terms of improving coronary functional status and reducing angina. However, if applied for the specific endotype of epicardial spasm, diltiazem is significantly better in reducing the burden of spasm, as compared with placebo.
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