Vast Majority of Patients With AF Receive Suboptimal Anticoagulation

March 15, 2017

The vast majority of patients with atrial fibrillation (AF) are not receiving optimal oral anticoagulant treatment, and this is causing a large number of strokes to occur that could have been prevented, new data show.

Another study shows that even if oral anticoagulants are prescribed, they are often not taken, and this is also contributing to higher stroke rates.

The first study, published in the March 14 issue of JAMA, analyzed data on 94,474 patients with acute ischemic stroke and a known history of AF admitted between 2012 and 2015 to 1622 hospitals participating in the "Get With the Guidelines–Stroke" program.

The researchers, led by Ying Xian, MD, Duke Clinical Research Institute, Durham, North Carolina, found that 84% of these patients had not been treated according to guideline recommendations in terms of oral anticoagulation before their stroke.

The study also showed that patients who were taking a non–vitamin K antagonist new oral anticoagulant (NOAC) or therapeutic-level warfarin had fewer strokes and those who did have strokes had less severe strokes, with lower mortality and better functional outcomes compared with patients not receiving guideline-recommended anticoagulant treatment.

"This study really highlights the burden of stroke and shows that if we can improve the use of oral anticoagulation we can reduce stroke rates and stroke severity," Dr Xian commented to Medscape Medical News.

Using figures of 700,000 ischemic strokes every year in the United States, of which about 10% to 15% are cardioembolic, Dr Xian and his colleagues estimated that between 58,000 and 88,000 strokes might be prevented every year if the anticoagulant treatment guidelines were better followed.

"That is a huge number, which would make an enormous difference to both patients and healthcare costs," Dr Xian said. "We must educate both doctors and patients better about the benefits of oral anticoagulants in AF."

Results of the study showed that 40% of these patients were taking only antiplatelet medications, 30% weren't taking any antithrombotic medication at all, and 14% were receiving subtherapeutic doses of warfarin.

Only 9% of patients were receiving a NOAC and only 8% were receiving warfarin at sufficient doses to achieve therapeutic levels.

When investigators looked just at patients at high risk for stroke (CHA2DS2-VASc score > 2), they found similar rates of suboptimal anticoagulation, with 83.5% of patients not receiving therapeutic warfarin or NOACs before stroke.

After adjustment for potential confounders and compared with no antithrombotic treatment, preceding use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio, 0.56, 0.65, and 0.88, respectively) and in-hospital mortality (adjusted odds ratio, 0.75, 0.79, and 0.83, respectively).

"The patients in our study had diagnosed AF before their stroke, but they are still massively undertreated," Dr Xian commented. 

The reasons behind the underuse of anticoagulation before stroke in these patients could not be identified from this study. However, after the stroke, reasons for not using anticoagulation were given as risk for bleeding in 16% of cases and risk for falls in 10% of cases.

"I imagine there would be similar reasons for not treating before the stroke," Dr Xian said.

But he points out that for two thirds of the patients, no reason was given for suboptimal treatment after the stroke.

He noted that it is well known that oral anticoagulants reduce stroke in patients with AF. "Some patients do have an increased bleeding risk so choose not to take these drugs, but the vast majority do not have a good reason for their suboptimal treatment. 

"I think doctors are aware of the benefits of oral anticoagulation, but I think they are underestimated and the concerns about bleeding are exaggerated for both doctors and patients," he added. "These are things that need to be addressed urgently in education programs."

Nonadherence Also a Major Problem

In the second study, published online in Heart on March 12, researchers looked at adherence to two NOACS, dabigatran or rivaroxaban, the first two such drugs to be made available, in 26,000 patients with AF in Ontario, Canada.

By linking prescription data and hospital admission data for these patients, the authors were able to establish which patients were adherent to their medication and the effect on stroke rates. Nonadherence was defined as a gap in treatment of 14 days or more.

Results showed that 36% of patients receiving dabigatran and 32% of those receiving rivaroxaban were no longer taking their medication at 6 months after the medication was first prescribed. These patients had a gap of at least 14 days in medication, and when the researchers looked at 30-day gaps the results were very similar.

The study also showed that the patients who were nonadherent had an 80% increased risk for stroke or death compared with those who continued to receive their medication correctly.

When the researchers looked at the risk for stroke or transient ischemic attack, this was even higher: Patients nonadherent to dabigatran had a 4-fold increased risk for stroke compared with those taking the drug properly, and the risk for stroke was 6-fold higher for patients nonadherent to rivaroxaban compared with those taking rivaroxaban correctly.

"These results are not that surprising," lead author, Cynthia Jackevicius, PharmD, professor of pharmacy practice at Western University of Health Sciences, Pomona, California, and the Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada, commented to Medscape Medical News. "If you stop a medication that protects you from a stroke, the risk of stroke will be higher. But we were a bit surprised by how much that risk seemed to increase."

She added: "NOACs have a very short duration of action — within 4 or 5 days they are completely out of the body. Warfarin has a much longer half-life. So short gaps in NOAC medication will increase the risk of stroke more so than similar gaps in warfarin use. I think many doctors and patients don't realize this. This is a big lesson to learn."

Dr Jackevicius also pointed out that, ironically, the main reason NOACs were thought potentially to result in better adherence may actually be the reason behind the poor adherence.  

"While NOACs are supposed to improve compliance because they don't need monitoring, it may be the fact that they are not monitored which contributes to the noncompliance as patients no longer have to see a health professional regularly who would be reminding them of the importance of taking their medication."

"We need more education," she added. "Patients, physicians, and pharmacists all need to understand the importance of taking these medications regularly and correctly. Physicians must not assume that patients are taking them as a third seem to stop taking them by 6 months."

It's not clear from these data why patients are stopping their medication, she noted. "Maybe they have a bleed and stop but don't restart. Or they might have a small bleed and or bruising and stop unnecessarily. Without a good dialogue with a physician or pharmacist, patients may stop inappropriately."

The study by Xian et al was supported by an award from the Patient-Centered Outcomes Research Institute. Dr Xian reported receipt of research funding to Duke Clinical Research Institute from the American Heart Association, Daiichi Sankyo, Janssen Pharmaceuticals, and Genentech. Disclosures for coauthors appear in the paper. The study by Jackevicius et al was funded by the Canadian Institutes of Health Research and the American Heart Association. The authors have disclosed no relevant financial relationships.

JAMA. Published online March 14, 2017. Abstract 

Heart. Published online March 12, 2017.  Abstract 

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