Chronic remote ischemic conditioning treatment in patients with chronic stable angina (EARLY-MYO-CSA): a randomized, controlled proof-of-concept trial

Abstract

Background: Chronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA.

Methods: The EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT).

Results: Among 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. - 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400-523] vs. 420 [330-475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups.

Conclusions: CSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population.

Trial registration: [chictr.org.cn], identifier [ChiCTR2000038649].

Keywords: Chronic remote ischemic conditioning; Chronic stable angina; Coronary heart disease; Myocardial flow reserve.

Fig. 1

CONSORT flow diagram for the study

Fig. 2

Comparison of myocardial flow outcomes at baseline and the 6-month follow-up evaluation. a There was no significant difference in the rest myocardial blood flow (MBF) between groups at baseline and 6 months; however, a significant change from baseline at 6 months was observed in the chronic remote ischemic conditioning (CRIC) group. b There was no significant difference in stress MBF between the groups at baseline; however, at 6 months, the CRIC group had significantly higher stress MBF and a greater change from baseline than the control group. c There was no significant difference in myocardial flow reserve (MFR) between groups at baseline; however, the CRIC group had a significantly higher MFR and greater change from baseline than the control group at 6 months. d There was no significant difference in reversible myocardial ischemia extent (RMIE) between the groups at baseline; however, the RMIE was significantly lower in the CRIC group than in the control group at 6 months. The CRIC group showed a greater change from baseline than the control group at 6 months

Fig. 3

The chronic remote ischemic conditioning (CRIC) showed a significant overall improvement in self-reported symptoms according to the Canadian Cardiovascular Society (CCS) with a change in the composition ratio of the different classifications at the time of follow-up

Fig. 4

Changes in the five dimensions of the Seattle Angina Questionnaire (SAQ) score at baseline and follow-up. The chronic remote ischemic conditioning (CRIC) group patients had improved scores in all five dimensions