Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network
Abstract
:1. Introduction
2. Methods
3. Results
4. Discussion
- Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period, while fluctuations of ADR rates were recorded for the other molecules (reduction in ICH ADRs for apixaban, increase in serious ADR and ICH ADR for edoxaban and dabigatran).
- Rate of serious ADR for rivaroxaban, edoxaban, and dabigatran significantly increased in the period 2019–2021 relative to the period 2017–2018, while no difference was found for apixaban. When normalizing serious ADR rates for usage rates for the same time periods, rivaroxaban showed the lowest risk index for all the study periods but 2019 (RI of 0.99 for rivaroxaban and RI of 0.83 for apixaban).
- Rate of ICH ADR for edoxaban significantly increased in the period 2019–2021 relative to the period 2017–2018, and a significant decrease was observed for apixaban, while no difference was found for rivaroxaban and dabigatran. When normalizing ICH ADR rates for usage rates for the same time periods, rivaroxaban constantly showed the lowest risk index for all the study periods, with RI as low as 0.59 in 2021.
- Rate of GI ADR remained stable during all the study periods for all DOACs, with apixaban and rivaroxaban showing the lowest RIs.
- Apixaban and rivaroxaban use was related to significantly lower rates of serious ADR and GI ADR as compared to dabigatran, while apixaban use resulted in a significantly higher rate of ICH ADR as compared to rivaroxaban.
- In the last five years, nosebleed was the most common ADR reported for rivaroxaban and apixaban, and anemia was the most common for edoxaban, while rectal bleeding was the most frequent ADR reported for dabigatran.
- Although the monthly number of DOACs remained stable during the study period, the total number of ADR reports progressively decreased from 2017 to 2021, pointing out the effect of the under-reporting phenomenon.
5. Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Serious ADR/Total ADR | 2017 | 2018 | 2019 | 2020 | 2021 | Serious/Total ADR 2017–2021 |
---|---|---|---|---|---|---|
Rivaroxaban | 53.2% (301/566) | 51.7% (304/588) | 63% (582/924) | 63.9% (354/554) | 61% (221/362) | 58.8% (1762/2994) |
Apixaban | 64.4% (308/478) | 61% (336/551) | 63.8% (444/696) | 53.7% (344/641) | 58.6% (259/442) | 60% (1691/2808) |
Edoxaban | 43.2% (63/146) | 45.2% (149/330) | 55.9% (257/460) | 69.7% (230/385) | 67.1% (194/289) | 55.5% (893/1610) |
Dabigatran | 50.5% (360/713) | 61.9% (445/735) | 64.8% (441/680) | 61.5% (297/483) | 82.8% (356/430) | 62.4% (1899/3041) |
Total serious ADR all DOACs/year | 1032 | 1234 | 1724 | 1225 | 1030 | 6245 |
ICH ADR/Total ADR | ||||||
Rivaroxaban | 8.8% (50/566) | 6.9% (41/588) | 8% (74/924) | 7.9% (44/554) | 8% (29/362) | 7.9% (238/2994) |
Apixaban | 13.2% (63/478) | 13.6% (75/551) | 12.8% (89/696) | 7.1% (46/641) | 11.3% (50/442) | 11.5% (323/2808) |
Edoxaban | 2% (3/146) | 4.2% (14/330) | 8.4% (39/460) | 6.7% (26/385) | 5.5% (16/289) | 6.1% (98/1610) |
Dabigatran | 8.5% (61/713) | 10.3% (76/735) | 9% (61/680) | 7.9% (38/483) | 13.5% (58/430) | 9.7% (294/3041) |
Total ICH ADR all DOACs/year | 177 | 206 | 263 | 154 | 153 | 953 |
GI ADR/Total ADR | ||||||
Rivaroxaban | 23.3% (132/566) | 21.4% (126/588) | 21% (194/924) | 22.9% (127/554) | 28.2% (102/362) | 22.7% (681/2994) |
Apixaban | 21.9% (105/478) | 21.6% (119/551) | 24% (167/696) | 18.6% (119/641) | 21.3% (94/442) | 21.5% (604/2808) |
Edoxaban | 21.2% (31/146) | 23% (76/330) | 23.7% (109/460) | 25.2% (97/385) | 30.4% (88/289) | 24.9% (401/1610) |
Dabigatran | 27.3% (195/713) | 31.3% (230/735) | 34.8% (237/680) | 31.5% (152/483) | 31% (133/430) | 31.1% (947/3041) |
Total GI ADR all DOACs/year | 463 | 551 | 707 | 495 | 417 | 2633 |
Study Year | 2017 | 2018 | 2019 | 2020 | 2021 |
---|---|---|---|---|---|
Rivaroxaban | 37.5 | 35.6 | 34.4 | 33.4 | 32.4 |
Apixaban | 32.6 | 31.7 | 31.6 | 32.2 | 32.7 |
Edoxaban | 5.8 | 10.9 | 14 | 16.2 | 16.3 |
Dabigatran | 24.1 | 21.8 | 20 | 18.2 | 18.7 |
Most Frequent ADR | Rivaroxaban | Apixaban | Edoxaban | Dabigatran |
---|---|---|---|---|
2017 | Nosebleed (9.7%) | Anemia (6%) | Nosebleed (8.3%) | Abdominal pain (10.5%) |
2018 | Nosebleed (11%) | Nosebleed (8%) | Nosebleed (9.5%) | Maelena (5.9%) |
2019 | Nosebleed (8.6%) | Nosebleed (8.6%) | Anemia (9.8%) | Rectal bleeding (9.8%) |
2020 | Nosebleed (12.8%) | Anemia (7.9%) | Anemia (9.7%) | Anemia (7.4%) |
2021 | Nosebleed (13.9%) | Nosebleed (10.4%) | Anemia (12.2%) | Rectal Bleeding (7.8%) |
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Lavalle, C.; Mariani, M.V.; Piro, A.; Magnocavallo, M.; Vetta, G.; Trivigno, S.; Forleo, G.B.; Della Rocca, D.G.; Uguccioni, M.; Russo, V.; et al. Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network. J. Clin. Med. 2022, 11, 3207. https://doi.org/10.3390/jcm11113207
Lavalle C, Mariani MV, Piro A, Magnocavallo M, Vetta G, Trivigno S, Forleo GB, Della Rocca DG, Uguccioni M, Russo V, et al. Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network. Journal of Clinical Medicine. 2022; 11(11):3207. https://doi.org/10.3390/jcm11113207
Chicago/Turabian StyleLavalle, Carlo, Marco Valerio Mariani, Agostino Piro, Michele Magnocavallo, Giampaolo Vetta, Sara Trivigno, Giovanni Battista Forleo, Domenico Giovanni Della Rocca, Massimo Uguccioni, Vincenzo Russo, and et al. 2022. "Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network" Journal of Clinical Medicine 11, no. 11: 3207. https://doi.org/10.3390/jcm11113207
APA StyleLavalle, C., Mariani, M. V., Piro, A., Magnocavallo, M., Vetta, G., Trivigno, S., Forleo, G. B., Della Rocca, D. G., Uguccioni, M., Russo, V., Summaria, F., & Di Lullo, L. (2022). Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network. Journal of Clinical Medicine, 11(11), 3207. https://doi.org/10.3390/jcm11113207