Table 2.
Results of the Delphi process to label oral anticoagulants according to the Fit-fOR-The-Aged (FORTA) classification
| Drug | FORTA classa | FORTA-A | FORTA-B | FORTA-C | FORTA-D | Number of ratersb | Consensus coefficient (cut-off 0.800) | Comments relevant for FORTA classification |
|---|---|---|---|---|---|---|---|---|
| Acenocoumarol | C | 9 | 1 | 10 | 0.95 | No new data; no appropriate data—user experience only | ||
| Fluindione | C | 8 | 1 | 9 | 0.944 | No new data; no appropriate data—user experience only | ||
| Phenprocoumon | C | 1 | 7 | 1 | 9 | 0.889 | No new data; no appropriate data—user experience only; meanwhile big observational studies comparing phenprocoumon with NOACs are published. The results are similar to the big NOAC trials. No RCTs, but there is no evidence that phenprocoumon is less effective and safe than warfarin; in one retrospective cohort study, rivaroxaban was superior compared with phenprocoumon | |
| Warfarin | B | 7 | 3 | 10 | 0.85 |
No new data; most data indicated inferiority, especially in the elderly. Overall, VKAs should be avoided in pts older than 75 years; wealth of clinical experience, INR provides reliable measurement of anticoagulation effect and suitable for use in valvular and non-valvular atrial fibrillation and in patients with mechanical heart valves but often ‘contraindicated’ in older patients due to inability to attend clinics regularly, polypharmacy, poor control Risk of ICH almost double that of NOAC agents in older patients, significant dietary and drug interactions and close monitoring required and variable dose scheduling; patients with impaired renal function, depending on the comorbidity, may require lower or higher dose of warfarin; older patients require lower doses |
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|
Dabigatran Low-intensity strategy (110 mg BID) |
B | 10 | 10 | 1 | Some new subgroup data, but results as before—it is probably safer but less potent than certain alternative DOACs; no relevant new data. However, renal safety issues are highly relevant in older patients and we do have at least one signal that dabi. 110 is not more effective concerning ICB in pts aged > 85 years; is as efficacious in preventing ischemic stroke as warfarin, safer than warfarin in terms of ICH/major bleeding, no significant close monitoring needed compared with warfarin, evidence shows renal function deteriorates faster in patients with CKD on warfarin than on dabigatran 110 mg BID and less drug interactions than warfarin but mainly renally excreted, large capsules to swallow and it cannot be removed from foil to be ‘blister packed’ | |||
|
Dabigatran High-intensity strategy (150 mg BID) |
B | 1 | 8 | 1 | 10 | 0.9 | Some new subgroup data, but results as before—dabi. 150 is probably more potent but less safe than dabi. 110; renal safety issues > low-intensity strategy; high-intensity strategy should be avoided in pts aged > 80 years and should be used with caution. New data demonstrating unsafety in older pts justify downgrade from B to C; more efficacious than warfarin in preventing ischemic stroke at high dose, safer than warfarin in terms of ICH, no significant close monitoring needed compared with warfarin, evidence shows renal function deteriorates faster in patients with CKD on warfarin than on dabigatran 150 mg BID and less drug interactions than warfarin but age interaction evident in RE-LY study on clinical findings with increased major bleeding in older groups compared with VKAs, mainly renally excreted, large capsules to swallow and it cannot be removed from foil to be ‘blister packed’ | |
|
Edoxaban High-intensity strategy only (60 mg OD) |
B | 3 | 7 | 10 | 0.85 | Falls data is reassuring but not generalizable to the real world, frail, older adult population; nor enough new data; once daily, no close monitoring needed compared with warfarin, as efficacious in preventing ischemic stroke as warfarin, reduced ICH and major bleeding compared with warfarin, no age interaction in safety or efficacy and strong safety data compared with warfarin in patients at high risk of falls | ||
| Rivaroxaban | B | 10 | 10 | 1 | No new data; overall the available new data do not support an upgrade from FORTA B to A. However, some data demonstrates that the kidney function might be more stable compared with VKA and there are still concerns about GI bleeding events; once daily, no close monitoring needed compared with warfarin, safer than warfarin in terms of ICH and less drug–drug interactions but higher rates of GI bleeding than warfarin and no reduction in overall major bleeding compared with VKA | |||
| Apixaban | A | 10 | 10 | 1 | No new data; available data supports FORTA A; as efficacious in preventing ischemic stroke as warfarin, enhanced safety with reduction in ICH and major bleeding compared with warfarin, no close monitoring needed compared with warfarin, no age interaction in trial findings, less drug interactions than warfarin and evidence of safety in patients with history of falls |
The FORTA class is depicted as well as the number of raters in each FORTA category. Comments were summarized from data, summary of product characteristics (SmPC) and raters’ comments (full versions are provided in Supplementary Tables 1 and 2, see ESM)
BID/BD twice a day, CKD chronic kidney disease, dabi. dabigatran, DOAC direct oral anticoagulant, FORTA Fit fOR The Aged, GI gastrointestinal, ICB intracranial bleeding, ICH intracerebral hemorrhage, INR International Normalized Ratio, NOAC non-vitamin-K oral anticoagulant, OD once daily, pts patients, RCT randomized controlled trial, VKA vitamin K antagonist
aProposed FORTA class in parenthesis if different from result
bTotal number of raters was 10