Table 3.

Association between overanticoagulation (INR ≥6.0), exposure to fluvoxamine or venlafaxine, stratified by CYP2C9 genotype

	Number of cases exposed to fluvoxamine or venlafaxine (n = 9)	Total cohort of genotyped acenocoumarol users (n = 2083)	HR*(95% CI)	P value for interaction
P value of multiplicative effect modification between fluvoxamine or venlafaxine and CYP2C9 variant alleles (wild type genotype/variant alleles)				0.49
P value for an additive effect modification between fluvoxamine or venlafaxine and CYP2C9 variant alleles (wild type genotype/variant alleles)				0.17
No use of fluvoxamine or venlafaxine, CYP2C9 wild type genotype	425	1346	1.00 reference
No use of fluvoxamine or venlafaxine, CYP2C9 variant alleles	219	702	1.08 (0.98, 1.19)
Use of fluvoxamine or venlafaxine, CYP2C9 wild type genotype	6	20	2.10 (1.18, 3.71)
Use of fluvoxamine or venlafaxine, CYP2C9 variant alleles	3	15	4.52 (0.63, 32.3)

Statistically significant values are printed in bold.

^*Adjusted for age, gender, BMI, target INR and use of nonsteroidal anti-inflammatory drugs, ATC-group M01A and proton pump inhibitors (A02 BC) In this time-dependent analysis, exposure in case patient and in the rest of the cohort is assessed at the time of the outcome in each case patient (index date). As control patients can be used multiple times, the number of assessments in the reference group is much larger than the number of individuals. Hence, crude RRs cannot be calculated from the data in this table.