Table 1 Bradford Hill criteria for causation
Criterion | Score | Note |
|---|---|---|
Strength | Moderate | The rate of AF among reports for SGLT2i was about halved compared to those for control drugs, or is about 2× for control drugs versus SGLT2i |
Consistency | High | Disproportionality changed little and remained significant in all sensitivity analyses. Therefore, the impact of unmeasurable confounders is likely to be negligible |
Specificity | Good | Positive and negative controls were satisfied |
Temporality and reversibility | Not assessed | Time from drug initiation to AE occurrence, as well as information on drug withdrawal and re-challenge was not available |
Biological gradient | Not assessed | We had no data on the dosage of SGLT2i. However, the gradient of SGLT2i dose is limited (max 2.5-fold) |
Plausibility | Satisfied | There are several potential mechanisms whereby SGLT2i may reduce the risk of AF |
Coherence | Good | Lower rates of AF among patients taking SGLT2i have been reported in randomized control trials, and in one of two observational studies |
Experimental support | Satisfied | Randomized controlled trials provide the most compelling experimental evidence for protection against AF by SGLT2i. Yet, it should be noted that none of such trials had AF as primary endpoint |
Analogy | Good | The FAERS has been used previously to demonstrate associations between AF rates and other specific drugs (e.g. ibrutinib) |