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Association of Vitamin K and Non-Vitamin K Oral Anticoagulant Use and Cancer Incidence in Atrial Fibrillation Patients.
Iftimi, AA, Rodríguez-Bernal, CL, Peiró, S, Bonanad, S, Ferrero-Gregori, A, Hurtado, I, García-Sempere, A, Sanfélix-Gimeno, G
Clinical pharmacology and therapeutics. 2022;(1):200-208
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Abstract
The association between the use of vitamin K antagonists (VKAs) and cancer risk reduction remains unclear. We aimed to assess the association between the use of VKAs or direct oral anticoagulants (DOACs) and the incidence of cancer in a large cohort of patients with atrial fibrillation (AF) by means of a population-based, propensity-weighted cohort study using population-wide databases including patients diagnosed with nonvalvular AF (NVAF) followed for up of 5 years (median 2.94 years). We created two cohorts based on the initiation therapy (VKA or DOAC). Initiation with VKA or DOAC was defined as filling a prescription with no previous exposure in the preceding 12 months. Cancer diagnoses of any type and for specific tumors (lung, colon, prostate, bladder, and breast). We included 39,989 patients, 31,200 (78.0%) in the VKA cohort. Incidence rate for any cancer was 12.45 per 1,000 person-year in the DOAC cohort vs. 14.55 in the VKA cohort (adjusted hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.02-1.32). In secondary outcomes, no differences were found for specific types of cancer, such as lung (HR: 1.28, CI: 0.89-1.83), colon (HR: 0.84, CI: 0.62-1.13), prostate (HR: 1.40, CI: 0.94-2.10), bladder (HR: 1.07, CI: 0.76-1.52), and breast (HR: 1.05, CI: 0.66-1.69). Sensitivity analyses yielded similar results. Subgroup analyses also produced consistent findings, except for men, for whom VKA was associated with a lower risk of colon cancer (HR: 0.68, 95% CI: 0.48-0.96). Our results do not confirm a chemoprotective effect of VKA when compared with DOAC in a large, real-world cohort of patients with NVAF followed for up to 5 years.
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Predictors of post-traumatic complication of mild brain injury in anticoagulated patients: DOACs are safer than VKAs.
Cipriano, A, Park, N, Pecori, A, Bionda, A, Bardini, M, Frassi, F, Lami, V, Leoli, F, Manca, ML, Del Prato, S, et al
Internal and emergency medicine. 2021;(4):1061-1070
Abstract
Although mild traumatic brain injury (MTBI) in people on oral anticoagulant treatment (OAT) is a frequent challenge for Emergency Department (ED), strong guidelines recommendations are lacking. In the attempt to assess the safety profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs), we have recruited 473 patients with a MTBI on OAT (43.6% males; age 81.8 ± 8.7 years), admitted to the Pisa's University Hospital ED (Jan 2016-Oct 2018). All patients underwent a head CT scan with those with no sign of acute bleedings remaining under clinical observation for the ensuing 24 h. Fifty patients (10.6%, 95% CI: 8.1-13.7%) had immediate intracranial hemorrhage (ICH), with a prevalence of patient-important outcomes due to immediate ICH of 1.1% (95% CI 0.4-2.4%); 3 patients died (0.6%, 95% CI 0.2-1.8) and 2 required neurosurgical intervention. Immediate ICHs were more frequent in VKA-treated than in DOAC-treated patients (15.9 vs. 6.4%. RR 2.5. 95%CI 1.4-4.4. p < 0.05). Multivariate analysis identified that post-traumatic amnesia, evidence of trauma above clavicles, high blood glucose, high blood pressure (BP) at arrival, and low prothrombin activity were predictors of immediate ICH. The prevalence of delayed ICH was 1.0% (95%CI 0.4-2.5%) without differences between DOACs and VKAs. Despite ICH being a frequent complication of MTBI in patients on OAT, immediate and delayed patient-important outcomes are rare. DOACs have a better safety profile than VKAs. Simple clinical parameters such as blood pressure at arrival or blood glucose might provide useful predictors of immediate ICH.Trial registration number: 11924_CIPRIANO. Local ethics committee approval number 33096.
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Shifting from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: predictors, patterns and temporal trends.
Shiyovich, A, Shalev, V, Chodick, G, Tirosh, M, Katz, A, Klar, MM, Shuvy, M, Pereg, D, Minha, S
BMC cardiovascular disorders. 2021;(1):493
Abstract
BACKGROUND Non-Vitamin K antagonist oral anticoagulants (NOACs) emerged as an alternative with comparable or superior efficacy and safety to vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). OBJECTIVES The aim of the current study was to investigate the patterns, predictors, timelines and temporal trends of shifting from VKAs to NOACs. METHODS In this retrospective observational study, the computerized database of a large healthcare provider in Israel, Maccabi Healthcare Services, was searched to identify patients with AF for whom either a VKA or NOAC was prescribed between 2012 and 2015. Time from diagnosis to therapy initiation and to shifting between therapies was evaluated. RESULTS Out of 6987 eligible AF incident patients, 2338 (33.4%) initiated treatment with a VKA and 2221 (31.7%) with a NOAC. In addition, 5259 prevalent patients were analyzed. During the study period, NOAC prescriptions proportion among the newly diagnosed cases increased from 32 to 68.4% (p for trend < 0.001). The median time from diagnosis to first dispensing was greater in NOAC than VKA and decreased among patients treated with NOAC during the study period (2012: 1.9 and 0.3 months, 2015: 0.7 and 0.2 months, respectively). During follow-up, 3737 (49%) patients (54.3% and 47.1% of the incident and prevalent cases, respectively), shifted from a VKA to a NOAC, after a median of 22 months and 39 months in the incident and prevalent cases, respectively, decreasing throughout the study period. Female gender, younger age, southern district, higher CHADS2 and CHA2DS2-VASC score, non-smoking, and treatment with antiplatelets were associated with a greater likelihood for therapy shift. Shifting from a NOAC to a VKA decreased over time from 8 to 4.5% in 2012 to 0.5% and 0.7% in 2015 in the incident and prevalent groups, p < 0.001 respectively. CONCLUSIONS Shifting from VKA to NOAC occurred in 50% of the cases, more frequently among incident cases, and younger patients with greater stroke risk. Shifting from a NOAC to a VKA was much less frequent, yet it occurred more often in incident cases and decreased over time. A socially and economically sensitive program to optimize the initiation of OAC therapy upon diagnosis is warranted.
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Factors Associated With the Choice of Oral Anticoagulant Class in the Older Patients: An Observational Study.
Pagès, A, Sabatier, R, Sallerin, B
Journal of cardiovascular pharmacology and therapeutics. 2020;(4):332-337
Abstract
AIM: Oral anticoagulants are the first-line drugs for treating thrombotic disorders related to nonvalvular atrial fibrillation and for treating deep vein thrombosis, diseases that increase in prevalence with age. Older patients have a greater risk of thrombotic and hemorrhagic events and are more prone to drug interactions. Given this backdrop, we wanted to determine the factors associated with the prescription of direct oral anticoagulants and vitamin K antagonists in older patients. METHODS We performed a cross-sectional observational study using a hospital prescription database. The study population consists of 405 older patients who were given oral anticoagulants. The 2 variables of interest were the prescription of 1 of the 2 classes of oral anticoagulants (direct oral anticoagulants vs vitamin K antagonists) and appropriateness of oral anticoagulant prescribing according to Summary of Product Characteristics (potentially inappropriate vs appropriate). RESULTS The factors associated with direct oral anticoagulant prescribing were the female gender (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.22-2.88) and initiation during hospital stay (OR: 2.56, 95% CI: [1.52-4.32]). Stage 4 and 5 chronic kidney diseases (OR: 0.39, 95% CI: [0.19-0.79] and OR: 0.07, 95% CI: [0.01-0.53]) were factors favoring vitamin K antagonist prescription. Being 90 years of age or more (OR: 2.05, 95% CI: [1.06-3.98]) was a factor for potentially inappropriate anticoagulant prescribing. The gastroenterology department (OR: 2.91, 95% CI: [1.05-8.11]) was associated with potentially inappropriate anticoagulant prescribing. CONCLUSIONS Direct oral anticoagulants are the drugs of choice for anticoagulant treatment, including in older adults. The female gender and the initiation during hospital stay increased the chances of being prescribed a direct oral anticoagulant in older adults. Stage 4 and 5 chronic kidney disease increased the likelihood of having a vitamin K antagonist prescribed. Our study also revealed a persistence of potentially inappropriate oral anticoagulant prescriptions in older patients.
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Ischemic Stroke and Transient Ischemic Attack Risk Following Vitamin K Antagonist Cessation in Newly Diagnosed Atrial Fibrillation: A Cohort Study.
Martinez, C, Wallenhorst, C, Rietbrock, S, Freedman, B
Journal of the American Heart Association. 2020;(2):e014376
Abstract
Background In nonvalvular atrial fibrillation (AF), oral anticoagulants prevent ischemic strokes and transient ischemic attacks (TIAs), but nonpersistence with vitamin K antagonist (VKA) oral anticoagulant therapy (20-50% at 1 year) is problematic. The precise risk of stroke/TIA after VKA cessation and its time course during extended follow-up is unknown. Methods and Results The study cohort of incident AF in patients receiving initial VKA between 2001 and 2013 was identified from the UK Clinical Practice Research Datalink (linked hospitalizations and causes of death). Using a nested case-control analysis, patients with incident stroke/TIA were matched to patients without stroke/TIA (controls). Relative risk with time since VKA cessation compared with current VKA use was approximated from conditional logistic regression. We studied 16 696 patients with incident AF and initial VKA treatment. There were 489 stroke/TIA cases matched to 2137 controls (mean CHA2DS2-VASc score 4.3). Compared with current VKA use, the excess incidence rate of stroke/TIA following VKA cessation in the first year after AF diagnosis was 2.29 (95% CI, 0.98-3.90) per 100 person-years of VKA cessation or 1 additional stroke/TIA per 43 patients per year discontinuing VKA, compared with 1.43 (95% CI, 0.97-1.88) per 100 person-years corresponding to 1 additional stroke/TIA per 70 patients per year, when VKA was discontinued more than 1 year after AF diagnosis. Conclusions VKA cessation is associated with a continuous excess thromboembolic stroke/TIA risk. Increasing oral anticoagulant persistence, especially in the year after AF diagnosis, should be a therapeutic target to reduce stroke/TIA in AF.
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Extent of arterial calcification by conventional vitamin K antagonist treatment.
Hasific, S, Øvrehus, KA, Gerke, O, Hallas, J, Busk, M, Lambrechtsen, J, Urbonaviciene, G, Sand, NPR, Nielsen, JS, Diederichsen, L, et al
PloS one. 2020;(10):e0241450
Abstract
BACKGROUND AND AIMS Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). METHODS We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007-2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1-99, 100-399, ≥400) was investigated by ordered logistic regression adjusting for covariates. RESULTS The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009-1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935-1.074). There was no significant interaction between VKA treatment duration and age on CAC category. CONCLUSIONS Adjusted for cardiovascular risk factors, VKA treatment-contrary to NOAC-was associated to higher CAC category.
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Direct Anticoagulants Versus Vitamin K Antagonists in Patients Aged 80 Years or Older With Atrial Fibrillation in a "Real-world" Nationwide Registry: Insights From the FANTASIIA Study.
Ortiz, MR, Muñiz, J, Esteve-Pastor, MA, Marín, F, Roldán, I, Cequier, A, Martínez-Sellés, M, Saldivar, HG, Bertomeu, V, Anguita, M
Journal of cardiovascular pharmacology and therapeutics. 2020;(4):316-323
Abstract
OBJECTIVE To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). METHODS A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. RESULTS Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 (P = .15), 3.45 vs 4.41 (P = .48), and 8.2 vs 11.0 (P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). CONCLUSION In this "real-world" registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.
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Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. The FANTASIIA study.
Anguita Sánchez, M, Bertomeu Martínez, V, Ruiz Ortiz, M, Cequier Fillat, Á, Roldán Rabadán, I, Muñiz García, J, Badimón Maestro, L, Esteve Pastor, MA, Marín Ortuño, F, ,
Revista espanola de cardiologia (English ed.). 2020;(1):14-20
Abstract
INTRODUCTION AND OBJECTIVES To compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study. METHODS The FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received. RESULTS A total of 2178 patients were included in the study (mean age 73.8±9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke-0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P=.032-, severe bleedings-2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044-, cardiovascular death-1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009-, and all-cause death-3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016-. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death. CONCLUSIONS Compared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain.
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Cancer-specific ischemic complications in elderly patients with atrial fibrillation: Data from the prospective ATHERO-AF study.
Pastori, D, Menichelli, D, Bucci, T, Violi, F, Pignatelli, P, ,
International journal of cancer. 2020;(12):3424-3430
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Abstract
Cancer may complicate the clinical course of nonvalvular atrial fibrillation (AF) but its association with cardiovascular events (CVEs) remains unclear. We performed a prospective cohort study including 2092 consecutive AF patients on vitamin K antagonists. Principal endpoint was the occurrence of CVEs including fatal/nonfatal myocardial infarction and ischemic stroke/transient ischemic attack and cardiovascular death. Secondary endpoints were major adverse cardiac events (MACEs) and thromboembolism (TE). Mean age was 73.7 ± 9.1 years and 42.1% were women; 367 (17.5%) patients had cancer: 21% gastrointestinal (GI), 10% respiratory, 28% genitourinary and 41% had other localization. Cancer patients were older but with similar comorbidities than those without. During a mean of 35.9 months, 203 CVEs occurred (incidence rate [IR] = 3.24 per 100 patient-years): 133 MACEs (IR = 2.12 per 100 patient-years) and 70 TE (IR = 1.12 per 100 patient-years). Multivariable Cox proportional hazards regression analysis showed an association between GI cancer and MACE occurrence (hazard ratio [HR] = 3.22, 95% confidence interval [CI] = 1.59-6.52, P = .001) and between respiratory cancer and TE (HR = 3.37, 95% CI = 1.30-8.75, P = .013). These associations were confirmed at competing risk analysis. In conclusion, AF patients with cancer have specific vascular outcomes according to cancer site, as indicated by the higher risk of MACE and TE in patients with gastrointestinal and respiratory cancer, respectively.
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Patient self-management of oral anticoagulation with vitamin K antagonists in everyday practice: clinical outcomes in a single centre cohort after long-term follow-up.
Corrochano, M, Jiménez, B, Millón, J, Gich, I, Rambla, M, Gil, E, Caparrós, P, Macho, R, Souto, JC
BMC cardiovascular disorders. 2020;(1):166
Abstract
BACKGROUND Patient self-management (PSM) of vitamin K antagonists (VKA) seems a very promising model of care for oral anticoagulation in terms of efficacy and safety. In comparison with other management models of VKA therapy, the number of scientific publications supporting the advantages of PSM is more limited. Currently, most of the scarce information comes from randomized clinical trials. Moreover, a small number of studies have assessed PSM of VKA therapy in real life conditions. METHODS We analyzed clinical outcomes of 927 patients in a single center (6018.6 patient-years of follow-up). Recruitment took place between 2002 and 2017. All patients followed a structured training program, conducted by specialized nurses. RESULTS Fifty percent of individuals had a mechanical heart valve (MHV), 23% suffered from recurrent venous thromboembolism (VTE) or high-risk thrombophilia, and 13% received VKA therapy because of atrial fibrillation (AF). Median follow-up was 6.5 years (range 0.1-15.97 years), median age was 58.1 years (IQR 48-65.9) and 46.5% were women. The incidence of major complications (either hemorrhagic or thromboembolic) was 1.87% patient-years (pt-ys) with a 95% CI of 1.54-2.27. The incidence of major thromboembolic events was 0.86% pt-ys (95% CI 0.64-1.13) and that of major hemorrhagic events was 1.01% pt-ys (95% CI 0.77-1.31). The incidence of intracranial bleeding was 0.22% pt-ys (95% CI 0.12-0.38). In terms of clinical indication for VKA therapy, the incidence of total major complications was 2.4% pt-ys, 2.0% pt-ys, 0.9% pt-ys and 1.34% pt-ys for MHV, AF, VTE and other (including valvulopathies and myocardiopathies), respectively. Clinical outcomes were worse in patients with multiple comorbidities, previous major complications during conventional VKA therapy, and in older individuals. The percentage of time in therapeutic range (TTR) was available in 861 (93%) patients. Overall, the mean (SD) of TTR was 63.6 ± 13.4%, being higher in men (66.2 ± 13.1%) than women (60.6 ± 13.2%), p < 0.05. CONCLUSIONS In terms of clinically relevant outcomes (incidence of major complications and mortality), PSM in real life setting seems to be a very good alternative in properly trained patients.