Table 2.
Characteristics of HF populations in non-vitamin K oral anticoagulant approval trials for stroke prevention in atrial fibrillation
| RE-LY [21] | ROCKET-AF [22] | ARISTOTLE [23] | ENGAGE-AF [24] | |
|---|---|---|---|---|
| Comparator to VKA | Dabigatran | Rivaroxaban | Apixaban | Edoxaban |
| Standard dose |
150 mg twice daily 110 mg twice daily |
20 mg once daily | 5 mg twice daily | 60 mg once daily |
| Reduced dose | – | 15 mg once daily | 2.5 mg twice daily | 30 mg once daily |
| Dose reduction criteria | 1:1:1 randomised to either dose or VKA | creatinine clearance 30–49 mL/min | at least two criteria: | At least one criterion: |
| Age ≥ 80 years | Estimated creatinine clearance 30–50 mL/min | |||
| Body weight < 60 kg | Body weight ≤ 60 kg | |||
| Serum creatinine ≥ 1.5 mg/dL | concomitant use: ciclo-sporine, dronedarone, ery-thromycin, or ketoconazole | |||
| Patients with heart failure (n) | 4904 (27% of trial patients) | 9033 (64% of trial patients) | 5943 (33% of trial patients) | 8145 (58% of trial patients) |
| Definition of heart failure | Presence of NYHA class ≥ II symptoms (fatigue, dyspnoea) in the 6 months prior to screening in patients with a history of previous admission for congestive HF. Information on LV-EF was only available in 59% of HF patients | History of HF or LV-EF < 40% | symptomatic congestive HF within 3 months or LV-dysfunction with an EF ≤ 40% | previous history of HF stage C or D according to AHA/ACC. LV-EF was available in 79% of HF patients |
| Patients with reduced LV-EF |
1258 (26% of HF population) |
2497 (27% of HF population) |
2736 (46% of HF population) |
3103/21,105 (38% of HF population) |
| Definition of reduced LV-EF | ≤ 40% | < 40% | ≤ 40% | < 50% |
| Mean age in HF population (years) | 68 | 72 | 69 | 70 |
| CHADS2 in HF population | 2.6 ± 1.1 | 3.7 ± 0.9 | 2.4 ± 1.1 | 3.0 ± 1.0 |
| Definition of primary safety endpoint | Major bleeding by study definition [21] | Composite of major and non-major clinically relevant bleeding by study definition [22] | Major bleeding defined by ISTH criteria [29] | Major bleeding defined by ISTH criteria [29] |
CHADS2 score to predict annual stroke risk in atrial fibrillation [45], HF heart failure, ISTH International Society on Thrombosis and Haemostasis, LV-EF left-ventricular ejection fraction, VKA vitamin K antagonist