The Prescription of Vitamin K Antagonists in a Very Old Population: A Cross-Sectional Study of 8696 Ambulatory Subjects Aged Over 85 Years
Abstract
:1. Introduction
2. Material and Methods
2.1. Design
2.2. Population
2.3. Collected Data
2.3.1. Data Concerning All Subjects
2.3.2. Data Concerning Subjects With VKA
2.4. Statistical Analysis
3. Results
3.1. Comparisons Between VKAG and noVKA
3.1.1. Sociodemographic Characteristics, the Presence of AF and/or VTE, and the RCD Number
3.1.2. Comorbidities Deduced from RCDs
3.1.3. Prescriptions
3.1.4. Cardiovascular Medications
3.2. Specific Analyses in VKAG and Comparison Between the 3 VKA Subgroups
3.2.1. Sociodemographic Characteristics and RCD
3.2.2. Indication VKA Prescription According to the RCD
3.2.3. Mean Number of Drugs Per Prescription
3.2.4. Cardiovascular Medications
3.2.5. Laboratory Monitoring
3.2.6. Comparison Between Novel and Refill VKA Prescriptions
3.2.7. Prescriber Specialty
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Rahman, F.; Kwan, G.F.; Benjamin, E.J. Global epidemiology of atrial fibrillation. Nat. Rev. Cardiol. 2014, 11, 639–654. [Google Scholar] [CrossRef] [PubMed]
- Go, A.S.; Hylek, E.M.; Phillips, K.A.; Chang, Y.; Henault, L.E.; Selby, J.V.; Singer, D.E. Prevalence of diagnosed atrial fibrillation in adults: National implications for rhythm management and stroke prevention: The AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001, 285, 2370–2375. [Google Scholar] [CrossRef] [PubMed]
- Wilke, T.; Groth, A.; Mueller, S.; Pfannkuche, M.; Verheyen, F.; Linder, R.; Maywald, U.; Bauersachs, R.; Breithardt, G. Incidence and prevalence of atrial fibrillation: An analysis based on 8.3 million patients. Europace 2013, 15, 486–493. [Google Scholar] [CrossRef] [PubMed]
- Ball, J.; Carrington, M.J.; McMurray, J.J.V.; Stewart, S. Atrial fibrillation: Profile and burden of an evolving epidemic in the 21st century. Int. J. Cardiol. 2013, 167, 1807–1824. [Google Scholar] [CrossRef]
- Heit, J.A.; Spencer, F.A.; White, R.H. The epidemiology of venous thromboembolism. J. Thromb. Thrombolysis 2016, 41, 3–14. [Google Scholar] [CrossRef] [Green Version]
- Münster, A.M.; Rasmussen, T.B.; Falstie-Jensen, A.M.; Harboe, L.; Stynes, G.; Dybro, L.; Hansen, M.L.; Brandes, A.; Grove, E.L.; Johnsen, S.P. A changing landscape: Temporal trends in incidence and characteristics of patients hospitalized with venous thromboembolism 2006–2015. Thromb. Res. 2019, 176, 46–53. [Google Scholar] [CrossRef]
- Kirchhof, P.; Benussi, S.; Kotecha, D.; Ahlsson, A.; Atar, D.; Casadei, B.; Castella, M.; Diener, H.C.; Heidbuchel, H.; Hendriks, J.; et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. J. Cardiothorac. Surg. 2016, 50, e1–e88. [Google Scholar] [CrossRef]
- Spyropoulos, A.C.; Merli, G. Management of venous thromboembolism in the elderly. Drugs Aging 2006, 23, 651–671. [Google Scholar] [CrossRef]
- Detournay, B. Coût direct des AVK en France. Arch. Cardiovasc. Dis. Suppl. 2016, 8, 174–179. [Google Scholar] [CrossRef]
- Roy, B.; Desai, R.V.; Mujib, M.; Epstein, A.E.; Zhang, Y.; Guichard, J.; Jones, L.G.; Feller, M.A.; Ahmed, M.I.; Aban, I.B.; et al. Effect of warfarin on outcomes in septuagenarian patients with atrial fibrillation. Am. J. Cardiol. 2012, 109, 370–377. [Google Scholar] [CrossRef] [Green Version]
- Ezekowitz, M.D.; Bridgers, S.L.; James, K.E.; Carliner, N.H.; Colling, C.L.; Gornick, C.C.; Krause-Steinrauf, H.; Kurtzke, J.F.; Nazarian, S.M.; Radford, M.J.; et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N. Engl. J. Med. 1992, 327, 1406–1412. [Google Scholar] [CrossRef] [PubMed]
- Wehling, M.; Collins, R.; Gil, V.M.; Hanon, O.; Hardt, R.; Hoffmeister, M.; Monteiro, P.; Quinn, T.J.; Ropers, D.; Sergi, G.; et al. Appropriateness of oral anticoagulants for the long-term treatment of atrial fibrillation in older people: Results of an evidence-based review and international consensus validation process (OAC-FORTA 2016). Drugs Aging 2017, 34, 499–507. [Google Scholar] [CrossRef] [PubMed]
- Kirchhof, P.; Benussi, S.; Kotecha, D.; Ahlsson, A.; Atar, D.; Casadei, B.; Castella, M.; Diener, H.C.; Heidbuchel, H.; Hendriks, J.; et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 2016, 37, 2893–2962. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Steffel, J.; Verhamme, P.; Potpara, T.S.; Albaladejo, P.; Antz, M.; Desteghe, L.; Haeusler, K.G.; Oldgren, J.; Reinecke, H.; Roldan-Schilling, V.; et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur. Heart J. 2018, 39, 1330–1393. [Google Scholar] [CrossRef] [Green Version]
- Hylek, E.M.; Evans-Molina, C.; Shea, C.; Henault, L.E.; Regan, S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007, 115, 2689–2696. [Google Scholar] [CrossRef] [Green Version]
- Plichart, M.; Berrut, G.; Maubourguet, N.; Jeandel, C.; Emeriau, J.P.; Ankri, J.; Bouvier, H.; Ruault, G.; Hanon, O. Use of vitamin k antagonist therapy in geriatrics: A French national survey from the French Society of Geriatrics and Gerontology (SFGG). Drugs Aging 2013, 30, 1019–1028. [Google Scholar] [CrossRef]
- Asgassou, S.; Hardel, A.; Dipanda, M.; Gauthier, J.; Da Silva, S.; Manckoundia, P.; Jouanny, P. Qualité et déterminants de l’équilibre de l’anticoagulation par AVK des sujets âgés: Étude d’une série continue de 155 patients hospitalisés en gériatrie aiguë. Geriatr. Psychol. Neuropsychiatr. Vieil. 2019, 17, 163–170. [Google Scholar]
- ICD-10 Version:2016. Available online: https://icd.who.int/browse10/2016/en/ (accessed on 2 June 2017).
- Martocchia, A.; Frugoni, P.; Indiano, I.; Tafaro, L.; Comite, F.; Amici, A.; Cacciafesta, M.; Marigliano, V.; Falaschi, P. Screening of frailty in elderly patients with disability by the means of Marigliano–Cacciafesta polypathology scale (MCPS) and Canadian Study of Health and Aging (CSHA) scales. Arch. Gerontol. Geriatr. 2013, 56, 339–342. [Google Scholar] [CrossRef]
- Wasmer, K.; Eckardt, L.; Breithardt, G. Predisposing factors for atrial fibrillation in the elderly. J. Geriatr. Cardiol. 2017, 14, 179–184. [Google Scholar]
- Mostaza, J.M.; Jiménez, M.J.R.; Laiglesia, F.J.R.; Peromingo, J.A.D.; Robles, M.B.; Sierra, E.G.; Bilbao, A.S.; Suárez, C. Clinical characteristics and type of antithrombotic treatment in a Spanish cohort of elderly patients with atrial fibrillation according to dependency, frailty and cognitive impairment. J. Geriatr. Cardiol. 2018, 15, 268–274. [Google Scholar]
- Nguyen, T.N.; Cumming, R.G.; Hilmer, S.N. The impact of frailty on mortality, length of stay and re-hospitalisation in older patients with atrial fibrillation. Heart Lung. Circ. 2016, 25, 551–557. [Google Scholar] [CrossRef]
- Lutz, J.; Jurk, K.; Schinzel, H. Direct oral anticoagulants in patients with chronic kidney disease: Patient selection and special considerations. Int. J. Nephrol. Renov. Dis. 2017, 10, 135–143. [Google Scholar] [CrossRef] [PubMed]
- HAS. Bon Usage du Médicament. Fibrillation Auriculaire non Valvulaire. Quelle Place Pour les Anticoagulants Oraux non Antivitamine K: Apixaban (Eliquis®), Dabigatran (Pradaxa®) et Rivaroxaban (Xarelto®). Available online: https://www.has-sante.fr/upload/docs/application/pdf/2013-07/fs_bum_naco_v5.pdf/ (accessed on 1 November 2019).
- Akl, E.A.; Kahale, L.A.; Barba, M.; Neumann, I.; Labedi, N.; Terrenato, I.; Sperati, F.; Muti, P.; Schünemann, H. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst. Rev. 2014, 7, CD006650. [Google Scholar] [CrossRef] [Green Version]
- Monte, S. Antithrombotic treatment is strongly underused despite reducing overall mortality among high-risk elderly patients hospitalized with atrial fibrillation. Eur. Heart J. 2006, 27, 2217–2223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gallo, P.; De Vincentis, A.; Pedone, C.; Nobili, A.; Tettamanti, M.; Gentilucci, U.V.; Picardi, A.; Mannucci, P.M.; Incalzi, R.A.; REPOSI Investigators. Drug-drug interactions involving CYP3A4 and p-glycoprotein in hospitalized elderly patients. Eur. J. Intern Med. 2019, 65, 51–57. [Google Scholar] [CrossRef]
- Mulhem, E.; Lick, D.; Varughese, J.; Barton, E.; Ripley, T.; Haveman, J. Adherence to medications after hospital discharge in the elderly. Int. J. Fam. Med. 2013, 2013, 901845. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alghamdi, F.; Chan, M. Management of heart failure in the elderly. Curr. Opin. Cardiol. 2017, 32, 217–223. [Google Scholar] [CrossRef]
- Martínez-Sellés, M.; Bayés de Luna, A. Atrial fibrillation in the elderly. J. Geriatr. Cardiol. 2017, 14, 155–157. [Google Scholar]
- Schäfer, H.; Kaiser, E.A.; Lotze, U. Increasing complexity: Which drug class to choose for treatment of hypertension in the elderly? Clin. Interv. Aging 2014, 9, 459–475. [Google Scholar] [CrossRef] [Green Version]
- Van Rein, N.; Biedermann, J.S.; Bonafacio, S.M.; Kruip, M.J.; van der Meer, F.J.; Lijfering, W.M. Statin use decreases coagulation in users of vitamin K antagonists. Eur. J. Clin. Pharmacol. 2016, 72, 1441–1447. [Google Scholar] [CrossRef] [Green Version]
- HAS. Les Anticoagulants Oraux. Available online: https://www.has-sante.fr/jcms/c_2851086/fr/les-anticoagulants-oraux/ (accessed on 1 November 2019).
- ANSM. Quoi de neuf concernant les Antivitamines K?—Point d’information. Available online: https://www.ansm.sante.fr/S-informer/Points-d-information-Points-d-information/Quoi-de-neuf-concernant-les-Antivitamines-K-Point-d-information/ (accessed on 1 November 2019).
Parameter | VKAG (N = 1157) | noVKAG (N = 7539) | p | |
---|---|---|---|---|
Age (years) | Mean ± SD | 89.98 ± 3.16 | 89.99 ± 3.33 | 0.912 |
Range | 85–03 | 85–109 | ||
% (N) | % (N) | 0.267 | ||
86–90 | 61.28 (709) | 62.06 (4679) | ||
91–95 | 32.15 (372) | 30.31 (2285) | ||
96–100 | 6.31 (73) | 7.04 (531) | ||
>100 | 0.26 (3) | 0.58 (44) | ||
Sex | Women | 53.67 (621) | 66.08 (4982) | <0.01 |
Men | 46.33 (536) | 33.92 (2557) | ||
Atrial fibrillation | 44.86 (519) | 11.37 (857) | <0.0001 | |
Venous thromboembolism | 5.18 (60) | 1.10 (83) | <0.0001 | |
Mean number of RCD | 2.21 ± 1.09 | 1.94 ± 1.04 | <0.01 |
Parameter | VKAG | noVKAG | Bivariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|---|---|
% (N) | % (N) | aOR (95% CI) | p | aOR (95% CI) | p | |
noRCD | 6.57 (76) | 28.04 (2114) | <0.01 | <0.01 | ||
RCD | 93.43 (1081) | 71.96 (5425) | ||||
Disabling stroke | 7.68 (83) | 7.58 (411) | 1.01 (0.79–1.29) | 0.945 | ||
Bone marrow failure and/or other chronic cytopenias | 0.19 (2) | 0.41 (22) | 0.45 (0.11–1.93) | 0.284 | ||
CAOD with ischemic manifestations | 8.14 (88) | 9.90 (537) | 0.76 (0.60–0.97) | 0.026 | 0.76 (0.59–0.97) | 0.030 |
Severe heart failure, arrhythmia, and/or atrial fibrillation | 73.64 (796) | 33.57 (1821) | 5.48 (4.73–6.35) | <0.01 | 5.50 (4.74–6.37) | <0.01 |
Diabetes mellitus (types 1 et 2) | 19.24 (208) | 21.44 (1163) | 0.87 (0.73–1.02) | 0.089 | ||
Neuropathy and/or myopathy and/or epilepsy | 0.83 (9) | 0.98 (53) | 0.88 (0.43–1.79) | 0.722 | ||
Severe hypertension | 24.88 (269) | 22.16 (1202) | 1.19 (1.02–1.39) | 0.025 | ||
Coronary artery disease | 19.89 (215) | 21.70 (1177) | 0.84 (0.71–0.99) | 0.037 | ||
Severe chronic respiratory failure | 5.55 (60) | 4.15 (225) | 1.27 (0.95–1.71) | 0.107 | ||
Alzheimer’s disease and severe neurocognitive disorders | 9.25 (100) | 14.93 (810) | 0.61 (0.49–0.76) | <0.01 | ||
Parkinson disease | 1.76 (19) | 2.84 (154) | 0.59 (0.37–0.96) | 0.035 | ||
Severe chronic nephropathy and/or PNS | 4.16 (45) | 2.64 (143) | 1.54 (1.09–2.17) | 0.014 | 1.45 (1.01–2.09) | 0.028 |
Polyarthritis nodosa and/or SLE and/or systemic scleroderma | 0.46 (5) | 0.76 (41) | 0.62 (0.24–1.56) | 0.308 | ||
Severe rheumatoid arthritis | 1.29 (14) | 2.10 (114) | 0.65 (0.37–1.13) | 0.126 | ||
Psychotic disorders | 2.87 (31) | 5.49 (288) | 0.54 (0.37–0.79) | <0.01 | 0.64 (0.43–0.94) | 0.024 |
Cancer and/or hematologic malignancy | 20.91 (226) | 24.98 (1355) | 0.74 (0.63–0.87) | <0.01 | ||
Other RCDs | 15.26 (165) | 12.09 (656) | 1.36 (1.13–1.64) | <0.01 | 1.41 (1.16–1.72) | <0.01 |
Illness leading to a serious medical condition | 2.31 (25) | 3.61 (196) | 0.67 (0.44–1.02) | 0.062 | ||
Non-exempting RCDs | 1.76 (19) | 2.03 (110) | 0.89 (0.54–1.45) | 0.630 |
Drugs | VKAG (N = 1157) | noVKAG (N = 7539) | p * | Fluindione (N = 688) | Warfarin (N = 431) | Acenocoumarol (N = 38) | p ** |
---|---|---|---|---|---|---|---|
% (N) | % (N) | % (N) | % (N) | % (N) | |||
Direct oral anticoagulants | 0.26 (3) | 9.19 (693) | <0.01 | 0 (0) | 0.70 (3) | 0 (0) | <0.01 |
Heparins | 1.38 (16) | 0.65 (49) | 0.01 | 0.87 (6) | 2.32 (10) | 0 (0) | 0.649 |
Fondaparinux | 0.09 (1) | 0.05 (4) | *** | 0.14 (1) | 0 (0) | 0 (0) | 0.053 |
Platelet aggregation inhibitors | 7.00 (81) | 32.43 (2445) | <0.01 | 7.27 (50) | 6.50 (28) | 7.89 (3) | <0.01 |
Beta-blockers | 38.12 (441) | 24.71 (1863) | <0.01 | 38.37 (264) | 37.82 (163) | 36.84 (14) | <0.01 |
Central ABA | 1.90 (22) | 2.56 (193) | 0.214 | 1.89 (13) | 2.09 (9) | 0 (0) | *** |
Peripheral ABA | 1.82 (21) | 1.84 (139) | 0.960 | 2.03 (14) | 1.39 (6) | 2.63 (1) | *** |
ACE inhibitors | 19.62 (227) | 15.07 (1136) | <0.01 | 21.22 (146) | 18.33 (79) | 5.26 (2) | <0.01 |
Angiotensin-receptor-blockers | 14.26 (165) | 11.22 (846) | <0.01 | 14.10 (97) | 13.92 (60) | 21.05 (8) | 0.013 |
Calcium-channel-blockers | 22.13 (256) | 19.18 (1446) | 0.021 | 22.53 (155) | 22.04 (95) | 15.79 (6) | 0.087 |
Nitrate derivatives | 7.00 (81) | 5.33 (402) | <0.01 | 7.56 (52) | 5.80 (25) | 10.53 (4) | 0.049 |
Other vasodilators | 3.46 (40) | 2.48 (187) | 0.06 | 4.65 (32) | 1.39 (6) | 5.26 (2) | *** |
Furosemide $ | 54.45 (630) | 25.79 (1944) | <0.01 | 54.07 (372) | 53.83 (232) | 68.42 (26) | 0.212 |
Spironolactone $ | 6.83 (79) | 3.32 (250) | <0.01 | 6.69 (46) | 6.03 (26) | 18.42 (7) | 0.014 |
Digoxin | 14.52 (168) | 3.18 (240) | <0.01 | 15.55 (107) | 12.76 (55) | 15.79 (6) | <0.01 |
Other antiarrhythmic drugs | 9.51 (110) | 4.44 (335) | <0.01 | 9.88 (68) | 9.28 (40) | 5.26 (2) | <0.01 |
Statins | 21.43 (248) | 17.80 (1342) | <0.01 | 23.11 (159) | 18.56 (80) | 23.68 (9) | 0.005 |
Fibrates | 2.51 (29) | 2.82 (213) | 0.604 | 2.91 (20) | 1.86 (8) | 2.63 (1) | *** |
Bile acid sequestrants | 0.09 (1) | 0.04 (3) | *** | 0 (0) | 0.232 (1) | 0 (0) | *** |
Other hypolipidemic drugs | 0.78 (9) | 0.48 (36) | 0.268 | 0.58 (4) | 0.93 (4) | 2.63 (1) | *** |
Parameter | VKA Subgroup | p | |||
---|---|---|---|---|---|
Fluindione (N = 688) | Warfarin (N = 431) | Acenocoumarol (N = 38) | |||
NDP | Mean ± SD | Mean ± SD | Mean ± SD | ||
Per subgroup | 6.73 ± 2.76 | 6.48 ± 2.81 | 7.32 ± 2.94 | 0.108 | |
According to the sex | Women | 6.79 ± 2.65 | 6.79 ± 2.87 | 6.89 ± 2.97 | 0.047 |
Men | 6.66 ± 2.88 | 6.09 ± 2.67 | 8.36 ± 2.73 | ||
According to the age range (years) | 86–90 | 6.68 ± 2.72 | 6.54 ± 2.83 | 7.55 ± 3.29 | 0.734 |
91–95 | 6.8 ± 2.92 | 6.32 ± 2.73 | 7 ± 2.51 | ||
96–100 | 7 ± 2.4 | 6.63 ± 3.08 | 7 ± 2.83 | ||
>100 | 4 * | 8 ± 1.41 | 0 | ||
According to the RCD | ≥1 RCD | 6.81 ± 2.76 | 6.45 ± 2.77 | 7.39 ± 3.01 | *** |
No RCD | 5.51 ± 2.52 | 6.81 ± 3.24 | 6 ** |
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Manckoundia, P.; Rosay, C.; Menu, D.; Nuss, V.; Mihai, A.-M.; Vovelle, J.; Nuémi, G.; d’Athis, P.; Putot, A.; Barben, J. The Prescription of Vitamin K Antagonists in a Very Old Population: A Cross-Sectional Study of 8696 Ambulatory Subjects Aged Over 85 Years. Int. J. Environ. Res. Public Health 2020, 17, 6685. https://doi.org/10.3390/ijerph17186685
Manckoundia P, Rosay C, Menu D, Nuss V, Mihai A-M, Vovelle J, Nuémi G, d’Athis P, Putot A, Barben J. The Prescription of Vitamin K Antagonists in a Very Old Population: A Cross-Sectional Study of 8696 Ambulatory Subjects Aged Over 85 Years. International Journal of Environmental Research and Public Health. 2020; 17(18):6685. https://doi.org/10.3390/ijerph17186685
Chicago/Turabian StyleManckoundia, Patrick, Clémentine Rosay, Didier Menu, Valentine Nuss, Anca-Maria Mihai, Jérémie Vovelle, Gilles Nuémi, Philippe d’Athis, Alain Putot, and Jérémy Barben. 2020. "The Prescription of Vitamin K Antagonists in a Very Old Population: A Cross-Sectional Study of 8696 Ambulatory Subjects Aged Over 85 Years" International Journal of Environmental Research and Public Health 17, no. 18: 6685. https://doi.org/10.3390/ijerph17186685