Is the folk medicine known as “The Secret” efficient in reducing bleeding after percutaneous coronary procedures?: a double-blinded, randomised trial

Study population and randomisation

We conducted a single-centre, double-blinded, randomised controlled trial with an allocation ration of 1:1.

All patients admitted to University and Hospital Fribourg for an elective invasive coronary procedure (diagnostic coronary angiography and/or percutaneous coronary intervention) aged over 18 years were eligible for inclusion. Patients having already contacted a “Secret Maker” to speak the formula on their behalf prior to the coronary angiography and those unable or unwilling to provide written informed consent and/or to participate in clinical follow-up were excluded. Patients with a major procedural complication (anaphylaxis, stroke, periprocedural myocardial infarction, pulmonary embolism, death) were likewise excluded.

Baseline patient and procedural characteristics were collected by dedicated study nurses during the index hospitalisation for elective coronary angiography. Clinical outcome was collected at discharge.

All patients underwent coronary angiography via the radial and/or femoral artery. Coronary angiography was performed according to good clinical practice using 5 F or 6 F diagnostic catheters at the operator’s discretion. Treatment modalities including devices used during percutaneous coronary intervention and antithrombotic management were at the physician’s discretion and according to the local standard of care at the time of the intervention.

A research nurse randomly assigned patients on the day of the intervention using sealed envelopes. Patients were randomised to receive standard care (C-group) or to receive standard care and “The Secret” (S-group).

The patients, cardiologists and nurses assessing bleeding outcomes were unaware of the patient’s group or the identity of the “Secret Maker”. Bleeding outcomes were classified and adjudicated internally by an event adjudication committee.

For the intervention group we asked “Secret Makers” to give the formula after study inclusion but prior to coronary angiography. The “Secret Makers”, 15 men and woman from an official list,6 agreed to participate in the study and were randomly selected on the same day from that list. The full name and birthday of the respective patient in the intervention group was communicated bytelephone to the Secret Maker, who then performed the blood charm sometime between study inclusion and coronary angiography. The exact wording of the charm to staunch bleeding was unknown to the investigators and might have differed from one “Secret Maker” to another.

All factors that could affect bleedings outcomes before, during and after the procedure were collected the day of the intervention and then compared by group. We also considered patients with high bleeding risk (HBR) depending on the definition of Academic Research Consortium High Bleeding Risk (ARC-HBR). Major and minor criteria are described by Urban et al.7 Patients were at HBR if at least one major or two minor criteria were met.

Clinical endpoints

The primary outcome was the rate of in-hospital bleeding according to the Bleeding Academic Research Consortium (BARC) consensus definition.8

The null hypothesis was that there is no difference in bleeding rate between the two groups, and the alternative hypothesis was that there was a significant difference in bleeding rate in one of the two groups. The study complied with the Helsinki Declaration and was approved by the local ethics committee (CER-VD 2021–01877). All patients provided written informed consent.

Statistical analysis

Categorical variables were reported as counts and percentages; continuous variables were reported as means and standard deviations. Normality was assessed by the computation of Q-Q plots and the Shapiro–Wilk test. Continuous variables were analysed using the Student’s t-test or the Wilcoxon rank-sum test per distribution. Categorical variables were compared using chi-square or Fisher exact test as appropriate. All statistical analyses were performed using dedicated software (StataCorp LP, College Station, Texas) at a two-tailed significance level of alpha=0.05.

Study population

Between January 2022 and July 2022, 238 patients were screened for enrolment. Thirty-four patients refused to participate and four had already called on a “Secret Maker” prior to the intervention to prevent bleeding. The final study population consisted of 200 patients. One hundred patients were randomised to receive “The Secret” and 100 patients were randomised to the control group.

Baseline patient and procedural characteristics

Baseline patient and procedural characteristics can be found in table 1. Mean age was 68±9 years and 74% (n=147) of the sample were men. Hypertension was found in 52.5% (n=105) of patients and its prevalence did not significantly differ between the groups (S-group: 46% (n=46) vs C-group: 59% (n=59), p=0.08). Dyslipidaemia was more prevalent in the C-group (62% (n=62)) than in the S-group (47% (n=47), p=0.03). Overall, 21% (n=48) of patients were on dual antiplatelet therapy before coronary angiography (S-group: 20% (n=20) vs C-group: 23% (n=23), p=0.49). Oral anticoagulation as standalone therapy was taken by 6% (n=6) in the S-group and 11% (n=11) in the C-group (p=0.21). No patient was on triple therapy. HBR-ARC minor and major bleeding criteria were evenly distributed across the two groups (S-group: 20% (n=20) vs C-group: 25% (n=25), p=0.40). Three percent (n=3) of patients in the C-group presented with definite thrombocytopenia compared with none in the S-group (p=0.08).

Overall, 75% (n=150) of patients believed in the healing power of the blood charm and there was no statistical difference with regard to that belief among the groups (S-group: 73% (n=73) vs C-group: 77% (n=77), p=0.51)).

There was a trend towards a more frequent use of the radial access in the C-group (64% (n=64) vs 51% (n=51), p=0.06). The concomitant periprocedural administration of aspirin and heparin was more frequent in the C-group (17% (n=17)) than in the S-group (7% (n=7)) (p=0.03). The periprocedural administration of other drugs was evenly distributed. Some 37% (n=37) of patients in the S-group and 41% (n=41) in the C-group received loading with a P2Y12 inhibitor after percutaneous coronary interventions (p=0.97).

The primary endpoint occurred in 27.5% (n=55) of patients. In the S-group 28% of patients (n=28) presented with BARC ≥1 bleeding whereas in the control group the rate of bleeding was 27% (n=27) (p=0.85). No major bleeding (BARC ≥3) occurred in either group.

Study limitations

This study is limited in size and is a single-centre study with homogenous practices among operators. Despite randomisation, there is also a trend for more patients in the control group to be treated by the radial approach. Since radial access has been shown to decrease major vascular complications and major bleeding, we cannot exclude the possibility that this difference between the two groups may have contributed to a bias and reduced the strength of the analysis.