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Which anticoagulant is the safest?


Apixaban was the clear winner in a large observational study looking at the risk of major bleeding and death with the use of the most commonly prescribed anticoagulants.

The study, which breaks new ground in terms of its scope and design, looked at around 200,000 new users of warfarin, dabigatran, rivaroxaban and apixaban in the UK primary care setting, tracking them over a five-year period. Overall, apixaban was found to be the safest direct oral anticoagulant (DOAC) compared with warfarin for patients with and without atrial fibrillation. Patients on a standard dose of apixaban had a 34% reduced risk of major bleeding and a 60% lower risk of intracranial bleeding over the study period, compared with warfarin. Apixaban users also had reduced rates of gastrointestinal bleeding.

The safety benefits of other DOACs compared with warfarin was less clear cut. There was a reduced risk of intracranial bleeds with rivaroxaban, but only in patients without atrial fibrillation. And in patients with atrial fibrillation, dabigatran lowered the risk of intracranial bleed, compared with warfarin.

Rivaroxaban was associated with higher all-cause mortality across the board, in patients both with and without atrial fibrillation, as was apixaban in low doses, compared with warfarin. But the authors say the higher mortality with these DOAC regimens could be due to closer monitoring of patients on warfarin, or due to prescribing choices related to underlying comorbidities.

The stronger safety profile of apixaban in this study is in line with a recent meta-analysis, which also showed apixaban to be the safest of the DOACs and a better performer than warfarin. But the authors of the present study say that meta-analysis mostly involved indirect rather than head-to-head comparisons. Direct comparison studies are few and far between, because regulatory authorities generally only require studies showing non-inferiority to placebo or standard treatment.

They add that their study is the first to look at a large subset of patients taking anticoagulants for reasons other than atrial fibrillation, such as after deep vein thrombosis, knee or hip replacement or stroke. This accounts for about half of users of anticoagulants.

Overall, they say their study paints a reassuring picture for patients taking DOACs as an alternative to warfarin, particularly for those who have been prescribed apixaban.

You can access the full study here.

The link between anticoagulation and dementia


Atrial fibrillation patients are much less likely to develop dementia if they are taking an anticoagulant, a large Swedish study has found.

Although the the increased risk of dementia in atrial fibrillation has been known for many years, until now it has been unclear whether anticoagulation modifies that risk.

The retrospective study is the largest yet to look at dementia and anticoagulation. It involved nearly half a million people, comprising everyone in Sweden who had been diagnosed with atrial fibrillation from 2006 to 2014, with a cumulative 1.5 million years of follow-up. The study found a surprisingly large number of people – 54% – were not taking an anticoagulant, the use of which is recommended to mitigate increased stroke risk.

But those who were on anticoagulation treatment had, on analysis, a 48% lower risk of developing dementia. The study results also suggested that the earlier a patient started on an anticoagulant, the less risk of developing dementia he or she had.

The researchers also found a greater effect in patients with higher risk of stroke according to their CHA2DS2-VASc score.

Despite previous suggestions that novel oral anticoagulants (NOACs) may be more effective at warding off dementia than warfarin, the researchers found no difference between the types of anticoagulant medications in dementia risk.

The researchers cautioned that because of the retrospective nature of the study, they could not demonstrate cause and effect. Randomised trials would never be done for ethical reasons, but given the biological plausibility of a causal effect, the results “strongly suggest” that anticoagulants protect against dementia, the authors said.

Other independent risk factors for dementia in the study were increasing age, Parkinson’s disease, earlier stroke and alcohol abuse.

Study co-author Dr Leif Friberg, an associate professor of cardiology at Stockholm’s Karolinska Institute, said the important implications from the findings were that patients should be started on anticoagulant treatment as soon as possible after diagnosis of atrial fibrillation and they should continue on the drugs.

“Doctors should not tell their patients to stop using oral anticoagulants without a really good reason. Patients start on oral anticoagulation for stroke prevention but they stop after a few years at an alarmingly high rate. If you know that AF eats away at your brain at a slow but steady pace and that you can prevent it by staying on treatment, I think most AF patients would find this a very strong argument for continuing treatment.”

Dr Friberg said atrial fibrillation patients often have a fatalistic view about stroke, thinking that either they’ll get it or they won’t. But they tend to be less fatalistic about dementia and are more likely to do what they can to ward off the disease. That may make risk of dementia a more compelling argument to ensure that patients stay on anticoagulation medication, Dr Friberg said.

You can read the study here.