Table 2.

Summary of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) quality of evidence assessment for each the predefined outcomes in both healthy volunteer and vasovagal syncope patient cohorts.

Quality Assessment							Number of Patients		Relative Risk (95% CI)	Quality
# Studies	Study Design	Risk of Bias	Inconsistency	Indirectness	Imprecision	Other	NET Inhibition	Control
Study Population: Pooled (Healthy Volunteers + Vasovagal Syncope Patients)
4	Double-Blind RCTs	Not serious	Serious	Not serious	Not serious	None	74	72	RR 0.32 [0.15, 0.72]	⊕⊕⊕⊕ Moderate†
Study Population: Healthy Volunteers
3	Double-Blind RCTs	Not serious	Not serious	Not serious	Not serious	None	45	45	RR 0.15 [0.04, 0.52]	⊕⊕⊕⊕ High
Study Population: Vasovagal Syncope Patients
1	Double-Blind RCTs	Not serious	Not serious	Not serious	Not serious	None	29	27	RR 0.49 [0.28, 0.86]	⊕⊕⊕⊕ High

Abbreviations: CI – confidence interval, RCT – randomized controlled trial, RR – relative risk

^†Moderate due to inconsistencies in syncope and syncope surrogate (i.e. severe vasovagal reaction with marked decreases in blood pressure and heart rate) outcome definitions, population characteristics, and head-up-tilt protocols