Trends in use of oral anticoagulants in older adults with newly diagnosed atrial fibrillation, 2010-2020 (November 2022)

This retrospective cohort study examined trends in oral anticoagulant (OAC) commencement and nonadherence in older (77 years old) adults with atrial fibrillation (AF) and coexisting geriatric conditions. There were 381,488 eligible patients from 2010 to 2020.

The analysis found a rise in OAC commencement in 2010 (20.2%) to 32.9% in 2020, 12 months after incidence of AF. DOAC uptake increased from 1.1% to 30.9% and warfarin initiation decreased from 19.1% to 2.0% during the study period.

Conditions which were associated with lower odds of OAC commencement included older age, dementia, frailty and anaemia. The review found that since the introduction of DOACs, beginning oral anticoagulation among this population group with AF has improved, however continued to remain suboptimal in 2020.

Efficacy and safety of the non-Vitamin K antagonist oral anticoagulant among patients with nonvalvular atrial fibrillation and cancer: A systematic review and network meta-analysis (November 2022)

This systematic review and network meta-analysis recalled 605 articles from databases, with only eleven having the inclusion criteria, and ten included patients with active cancer. The cohort consisted of 277,652 patients, 199,603 received coumadin and 78,049 a non-vitamin K antagonist oral anticoagulant (NOAC). The mean age was 63.5 years old with a follow-up duration ranging from 0.6 to 2.8 years.

The review found that NOACs were linked to a lower incidence of major bleeding and combined stroke in patients with atrial fibrillation and cancer compared with warfarin. There was a reduced occurrence of intracranial and major gastrointestinal bleeding in patients who received NOACs compared with warfarin.

The results of this analysis should be interpreted with caution as the meta-analysis was primarily run by observational studies which receive the risk of selection bias, measurement biases and potential residual confounders. The analysis also included a higher proportion of patients (71.8%) who were being treated with warfarin, giving the possibility that the patients receiving NOACs may be selectively healthier compared to the warfarin group. Despite these limitations, this analysis represents the best available data which supports the use of NOACs, at least, as effective and safe as warfarin. Further randomised controlled trials which focus on patients with cancer and atrial fibrillation are recommended for more definitive evidence.

Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis (October 2022)

Worldwide guidelines recommend NOACs (apixaban, dabigatran, edoxaban and rivaroxaban) are used to prevent stroke in AF patients, compared with warfarin. NOACs are endorsed as the safer, first-line therapy with respect to serious bleeding.

This systematic review and meta-analysis included 106 studies. The meta-analysis found that off-label underdosing was associated with a null effect on stroke outcomes compared with recommended NOAC dosing. Examination of 15 studies found inappropriate NOAC dosing had a null effect of underdosing on major bleeding, however an increased risk of all-cause mortality.

Analysis of 12 studies investigating the drivers of inappropriate NOAC dosing found older age, history of minor bleeds, hypertension, congestive heart failure and lower creatine clearance were associated with an increased risk of underdosing. This review proposes that off-label underdosing of NOAC’s does not reduce bleeding outcomes and increases all-causes mortality risk among AF patients.

Temporal trends and patterns in atrial fibrillation incidence (June 2022)

This UK population-based study consisted of approximately 3.4 million individuals, aged ≥16 years between January 2, 1998 and December 31, 2017. The incidence of AF increased by 30% during that period with the rate leveling out from 2012.

The age standardised incidence of AF was higher in men than in women, which was consistent across age groups and remained stable over time.  Men were also younger than women at date of diagnosis. Socioeconomic status was a factor, showing less affluent status being more likely to experience AF and having more comorbidities.

Increases in AF incidence may be contributed to changes in clinical practice and the detection of AF which were not historically diagnosed. An increase in the number of older people within the population, could indicate a significant rise in total cases, where a shift in the age distribution towards older age groups has been widely observed. The study found that the proportion of AF diagnosis was first made in hospital when AF was not the primary reason for admission.

“Clinical thresholds for investigation for AF and documentation of diagnosis may have been altered by the torrent of evidence since the early 1990s for effectiveness of oral anticoagulation in stroke prophylaxis”. The observed differences in AF incidence highlight opportunities for more targeted prevention strategies and resource utilisation to aim for health equity.

Knowledge about atrial fibrillation and anticoagulation affects the risk of clinical outcomes (May 2022)

The European Society of Cardiology, European Heart Rhythm Association, and Canadian Heart Rhythm Society believe it is important to provide education about AF and OAC to all patients; however, what type and level of information is unknown. This small study consisted of 174 AF patients with the majority receiving non-Vitamin K anticoagulants - rivaroxaban (51.3%), apixaban (26.0%), and dabigatran (22.6%).

The medium follow-up period was 42 months, where 12 patients had arterial thromboembolic events, 29 bleeding episodes and 15 deaths. The results found that the patients who experienced ischaemic cerebrovascular events were less aware of the importance of a regular anticoagulant intake despite the lack of AF symptoms compared to those who did not have any AF complications.

Despite being a small population sample, these results are consistent with other research finding that a poor OAC regime is associated with stroke in AF patients. Regular intake should be emphasised by the patient’s health professional during consultation.

The Prognostic Nutritional Index may predict left atrial appendage thrombus or dense spontaneous echo contrast in patients with Atrial Fibrillation (April 2022)

Atrial fibrillation (AF) is the most sustained cardiac arrhythmia in the clinical setting and ischemic stroke is one of the most severe complications caused by AF with approximately 90% of thrombi originating in the left atrial appendage (LAA).  The prognostic nutritional index (PNI) is an independent predictor of adverse outcomes in patients with cardiovascular diseases and the presence of LAAT or spontaneous echo contrast (SEC) is associated with ischemic stroke. SEC is also a marker for a hypercoagulable state.

PNI comprised of serum albumin and lymphocyte count that reflects the immunonutritional status and has shown to be associated with poor outcomes of cardiovascular diseases. In recent literature, low PNI was reported as an independent predictor for AF incidence and AF recurrence after ablation. As it is unknown if PNI could function as a prognostic biomarker for LAAT/dense SEC, the aim of this study was to investigate the relationship between the PNI and LAAT/dense SEC in patients (n=406) with non-valvular AF. The research was carried out from March 2015 to February 2019.

As PNI is a multifactorial indicator of inflammation (lymphocytes) and nutritional status (serum albumin), the research findings may be explained as follows:

Low PNI demonstrated malnutrition - haemoglobin and total cholesterol levels were significantly lower in subjects with a low PNI. Once LAAT is detected, oral anticoagulants should be prescribed. Warfarin and NOACs have been proven to be effective in the treatment of LAAT, however, in patients with nutritional problems, food interaction may influence the efficacy of OACs for thromboembolic prevention. Switching to DOACs may be preferred due to few food interactions.

Inflammation may play a role in the thrombogenic setting. Although neutrophil count was comparable between patients with high and low PNI values, it was significantly higher in patients with LAAT/dense SEC than in those without LAAT/dense SEC. International Normalised Ratio, an inflammatory marker, was greater in patients with either increased PNI values or LAAT/dense SEC. Previous studies demonstrated that there was a link between thrombogenesis and inflammation.

Results found that lymphocyte count and serum albumin were both lower in patients with LAAT/dense SEC. Multivariate logistic regression analysis showed that the PNI was an independent predictor for LAAT/dense SEC. LAAT/dense SEC in patients with a PNI ≤48.0 was approximately 2.6-fold higher than that in those with a PNI > 48.0. Therefore, PNI may be considered a predictor for LAAT/dense SEC, however further larger prospective studies are required to validate these findings. 

Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study (April 2022)

Current treatments recommended for AF is direct oral anticoagulants (DOACs) due to their safety and efficacy over vitamin K antagonists. Based on results from observational data from patients with inherited factor XI deficiency, the researchers hypothesised that treatment with asundexian would lead to less bleeding compared to DOACs. This research compared the DOAC, apixaban with the activated coagulation factor XIa inhibitor asundexian, which might reduce thrombosis and with minimal effect on haemostasis.

The study took place between January 2020 and June 2021, with 753 patients from 93 sites in 14 countries starting the treatment phase. There were three treatment groups – 249 receiving 20mg of asundexian; 254 receiving 50mg of asundexian; and 250 participants receiving the standard dosing of 5mg twice daily of apixaban. At the end of the treatment phase, 671 completed and 82 did not due to various reasons – adverse events (38), death (6), withdrawal (12), non-adherence (1) and other reasons (25).

The main outcome was the composite of major bleeding or clinically relevant non-major bleeding, according to International Society on Thrombosis and Haemostasis criteria. At the end of the treatment phase there were three events from the asundexian 20mg group; one event from the asundexian 50mg group, and six events from the apixaban group.

Therefore, the study concluded that asundexian treatment resulted in significantly lower rates of bleeding compared to apixaban: the drug is well tolerated with only 1 in 20 participants discontinuing the treatment due to an adverse event. In conclusion, these result demonstrate the efficacy of FXIa as a therapeutic target and provides a rationale for further larger clinical trials with asundexian.

Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study (Jan 2022)

This retrospective cohort study used a database of 3.5 million people over a 3-year period (2014-2017). As edoxaban was the most recent (2015) non-Vitamin K oral anticoagulant (NOAC) introduced in Germany as a treatment option for AF, the study objective was to compare edoxaban’s efficacy compared to other NOACs (dabigatran, rivaroxaban and apixaban in 2011) and Vitamin K oral anticoagulants (VKA). These therapies were examined for the prevention of ischaemic stroke, systemic embolism and major bleeding.

Results showed that per 100 person-years, the incidence of thromboembolic events was edoxaban (2.33); apixaban (3.45); dabigatran (2.96) and VKA (4.41). For major bleeding the incidence rate was also lower for edoxaban at 3.07 per 100 person-years compared with apixaban (3.38); dabigatran and rivaroxaban (4.22); and VKA (7.41).

These findings demonstrate the safety and effectiveness of edoxaban when compared to other current NOACs and VKA. The results showed statistically significant lower combined risks of ischaemic stroke, systemic embolism and major bleeding.

Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation (Dec 2021)

This retrospective cohort study comprised of 581,451 patients aged 65 years, with atrial fibrillation (AF) that were treated with anticoagulant therapy. From this group 227,572 were prescribed rivaroxaban and 353,879 patients made up the apixaban group. The study period was between January 1, 2013, and November 30, 2018, consisting of 474,605 person-years of follow-up. The median follow-up for patients in the rivaroxaban group was 174 (62-397) days and 176 for those taking apixaban.

Results found that patients receiving rivaroxaban had increased risk for major ischaemic haemorrhagic events; fatal ischaemic/haemorrhagic events; non-fatal and fatal extracranial bleeding; and total mortality. The investigation included different does of both anticoagulants – standard dose (5mg twice daily for apixaban and 20mg once daily for rivaroxaban) or a reduced dose (2.5mg twice daily for apixaban and 15mg once daily for rivaroxaban). Despite a reduced dose, rivaroxaban still showed increased risk across all events. Patients who were being treated with rivaroxaban were more likely to discontinue this treatment or change to a different oral anticoagulant than the patients from the apixaban group.