Low dose anticoagulation not without risks “real-world” trial shows  


By Sunalie Silva

10 Oct 2019

Low dose anticoagulation is associated with higher bleeding and thrombotic events in frail patients with non-valvular AF compared to those receiving full dose anticoagulation, according to findings from the first real world Australian data to report DOAC safety in high-risk patients.

Investigators from the Northern Hospital in Victoria who conducted the retrospective analysis say that while low dose anticoagulation may be a suitable alternative for some high-risk patients, it should not be considered the default option for all because it negates neither bleeding or thrombotic risk in these patients.

They were able to analyse the appropriateness of DOAC prescriptions in 459 patients who had commenced or continued on a blood thinner between 2013 and 2016.

Their findings revealed that just over a third of patients (36.2%) were not appropriately dosed.

Speaking to the limbic Dr Prahlad Ho, director of clinical haematology at Northern Health, Sydney, and lead investigator on the study said the cohort was older – the median age of patients was 75 years – frail and had high comorbidity.

“The primary challenge for treating clinicians is the difficulty of balancing the thrombosis and bleeding risk particularly in this group of high risk, frail patients complicated by concurrent medical co-morbidities – how we use DOACs in this group is still really quite unclear.”

It’s a challenge Dr Ho says is highlighted in AF by the number of overlapping risk factors seen in both the CHA2DS2-VASC score used to estimate annual stroke risk and the HAS-BLED score used to stratify major bleeding risk.

To address this delicate balance, low dose anticoagulation is widely used by physicians as a compromise particularly in the elderly and frail populations says Dr Ho adding that low dose anticoagulation was used in 43.3% of patients analysed in the study.

But contrary to the perception that low dose anticoagulation is a safer option in terms of bleeding, findings from the study suggests that low dose anticoagulation is associated with both increased bleeding (p=0.023) and thrombotic stroke (p=0.034) when compared to those receiving full dose anticoagulation.

“One reason for this may be that the low dose is more commonly used in high-risk patients with co-morbidities such as older age, renal impairment and higher falls risk but what our study highlights is that low dose anticoagulation does not mitigate bleeding risk in these individuals,” said Dr Ho.

There were 33 (5%) deaths captured during the follow up period including four (0.6%) due to bleeding complications.

Dr Ho said these four patients were all over the age of 70 and on low dose anticoagulation. Two had contraindications to DOAC prescription according to AMH guidelines, one due to severe renal impairment and one due to Child Pugh C liver cirrhosis.

Meanwhile there was no mortality due to thrombotic stroke.

There were 26 (4.0%) episodes of clinically significant bleeding (ISTH-SSC bleeding assessment score of ≥3) while on anticoagulation with an overall rate of 3.13 per 100 person-years.

Significant risk factors for clinically significant bleeding included low dose anticoagulation, reduced renal function (eGFR 30-59 ml/min/1.73m2), history of bleeding, high falls risk and CHA2DS2-VASC score ≥4.

What’s more, the event rate of patients on low dose DOACs was higher, 5.05 per 100 person-years compared to 1.82 per 100 person-years for full dose. There was also a trend towards increased risk with concurrent antiplatelet therapy (p=0.05).

The initial 3 months on anticoagulation conferred the highest rate of bleeding complications with an event rate of 7.80 per 100 person-years. For patients who did not bleed in the first 3 months the rate of bleeding decreased significantly to 2.07 per 100-person-year.

Dr Ho also pointed out that no significant difference was observed in bleeding rates between the different DOACs.

“If you put someone on a low dose blood thinner don’t assume that they will have only minimal risk of bleeding. For elderly frail patients the need for careful patient selection and individualised decision making, in discussion with the patient or their family, is critical,” suggests Dr Ho.

He also recommends ongoing review of the risk-benefit ratio in frail patients.

“Because that profile changes with changes with time – their risk today may be very different to their risk in a year’s time and in the elderly and frail that can change in a matter of months so you have to continuously monitor these patients.”

Access the study here.

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