Dataset Information

A novel method to interpret early phase trials shows how the narrowing of the coronary sinus concordantly improves symptoms, functional status and quality of life in refractory angina.

ABSTRACT:

Background

Reduction of the coronary sinus was shown to improve angina in patients unsuitable for revascularisation. We assessed whether a percutaneous device that reduces the diameter of the coronary sinus improved outcomes across multiple endpoints in a phase II trial.

Methods

We conducted a novel analysis performed as a post hoc efficacy analysis of the COSIRA (Coronary Sinus Reducer for Treatment of Refractory Angina) trial, which enrolled patients with Canadian Cardiovascular Society (CCS) class 3-4 refractory angina. We used four domains: symptoms (CCS Angina Scale), functionality (total exercise duration), ischaemia (imaging) and health-related quality of life. For all domains, we specified a meaningful threshold for change. The primary endpoint was defined as a probability of ≥80% that the reducer exceeded the meaningful threshold on two or more domains (group-level analysis) or that the average efficacy score in the reducer group exceeded the sham control group by at least two points (patient-level analysis).

Results

We randomised 104 participants to either a device that narrows to coronary sinus (n=52) or a sham implantation (n=52). The reducer group met the prespecified criteria for concordance at the group level and demonstrated improvement in symptoms (0.59 CCS grade, 95% credible interval (CrI)=0.22 to 0.95), total exercise duration (+27.9%, 95% CrI=2.8% to 59.8%) and quality of life (stability +11.2 points, 95% CrI=3.3 to 19.1; perception +11.0, 95% CrI=3.3 to 18.7).

Conclusions

The reducer concordantly improved symptoms, functionality and quality of life compared with a sham intervention in patients with angina unsuitable for coronary revascularisation. Concordant analysis such as this one can help interpret early phase trials and guide the decision to pursue a clinical programme into a larger confirmatory trial.

Trail registration number

ClinicalTrials.gov identifier: NCT01205893.

SUBMITTER: Jolicoeur EM

PROVIDER: S-EPMC8641517 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMany patients with coronary artery disease who are not candidates for revascularization have refractory angina despite standard medical therapy. The balloon-expandable, stainless steel, hourglass-shaped, coronary-sinus reducing device creates a focal narrowing and increases pressure in the coronary sinus, thus redistributing blood into ischemic myocardium.MethodsWe randomly assigned 104 patients with Canadian Cardiovascular Society (CCS) class III or IV angina (on a scale from I to IV, with higher classes indicating greater limitations on physical activity owing to angina) and myocardial ischemia, who were not candidates for revascularization, to implantation of the device (treatment group) or to a sham procedure (control group). The primary end point was the proportion of patients with an improvement of at least two CCS angina classes at 6 months.ResultsA total of 35% of the patients in the treatment group (18 of 52 patients), as compared with 15% of those in the control group (8 of 52), had an improvement of at least two CCS angina classes at 6 months (P=0.02). The device was also associated with improvement of at least one CCS angina class in 71% of the patients in the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52) (P=0.003). Quality of life as assessed with the use of the Seattle Angina Questionnaire was significantly improved in the treatment group, as compared with the control group (improvement on a 100-point scale, 17.6 vs. 7.6 points; P=0.03). There were no significant between-group differences in improvement in exercise time or in the mean change in the wall-motion index as assessed by means of dobutamine echocardiography. At 6 months, 1 patient in the treatment group had had a myocardial infarction; in the control group, 1 patient had died and 3 had had a myocardial infarction.ConclusionsIn this small clinical trial, implantation of the coronary-sinus reducing device was associated with significant improvement in symptoms and quality of life in patients with refractory angina who were not candidates for revascularization. (Funded by Neovasc; COSIRA ClinicalTrials.gov number, NCT01205893.).

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