Table 4.
Comparison of the three landmark prospective randomized controlled trials
| EU-PACT 2013 | COAG 2013 | GIFT 2017 | |
|---|---|---|---|
| Number of patients. | 455 | 1015 | 1597 |
| Mean age | 67 | 58 | 72 |
| Race | 98% Caucasians | 67% Caucasians | 91% Caucasians |
| Comparator | Fixed dosing | Clinical dosing | Clinical dosing |
| Genotype guided dosing duration | Five days | Five days | Eleven days |
| Indications | AF and VTE | AF and VTE | DVT prevention in hip and knee replacement |
| CYP4F2*3 | Not tested | Not tested | tested |
| Genetic algorithm used | IWPC algorithm | Gage et al. algorithm | Gage et al. algorithm |
| 1ry outcome | PTTR | PTTR | Composite of: major bleeding within 30 days, INR of 4 or greater within 30 days, death within 30 days, and symptomatic or asymptomatic VTE within 60 days of arthroplasty |
| Result |
Genotype-guided dosing was associated with an increased PTTR (adjusted difference = 7%, 67.4% vs. 60% P < 0.001). |
Genotype-guided dosing was not associated with an increased PTTR (adjusted difference= -0.2%, 45.2% vs. 45.4% P = 0.91). |
Genotype-guided dosing was associated with a lower 1ry composite outcome (absolute difference, 3.9%, 10.8% vs. 14.7%, P = 0.02). |
| Strengths | Study population of same ethnic background | Using Clinical dosing as a comparator (which showed better R2 and MAE when compared to fixed dosing) |
Large sample size. Tested for CYP4F2*3 in addition to the other genetic variants. |
| Limitations | Using fixed warfarin dosing as a comparator. (although it could be argued that this may resemble actual practice and increase generalizability of the study) | Included 27% African patients who were tested for genetic variants that were not prevalent in their population. Upon exclusion of the African patients’ data from the analysis, there was a higher PTTR in the genetic guided warfarin dosing (48.8 vs. 46.1%; P = 0.15) |
Mostly elderly patients. Results of the patients’ genotyping was available before initiation. Composite outcome result mainly driven by the INR > 4 outcome. |
AF: Atrial fibrillation, CYP4F2*3: Cytochrome 450 4F2*3, DVT: Deep vein thrombosis, INR: International normalized ratio, PE: Pulmonary embolism, PTTR: Percentage time in therapeutic range, VTE: Venous thromboembolism