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Nonpersistence to treatment with NOACs high among AF patients

Jairia Dela Cruz
2 months ago

Premature discontinuation of treatment with novel oral anticoagulants (NOACs) occurs frequently in clinical practice, according to a study, with about one in three patients becoming nonpersistent to dabigatran or rivaroxaban within 6 months of drug initiation. This practice may have detrimental effects, leading to stroke, transient ischaemic attack (TIA) or death.

The retrospective cohort study included atrial fibrillation (AF) patients who used dabigatran (n=15,857; mean age 80.68 years; 52.2 percent female) or rivaroxaban (n=10,119; mean age 76.96 years; 52.8 percent female). A gap of ≥14 days in dabigatran or rivaroxaban prescriptions determined nonpersistence.

At 6 months, more than 30 percent of patients in each treatment group were nonpersistent to their medications (dabigatran, 36.4 percent; median time to nonpersistence, 240 days; rivaroxaban, 31.9 percent; median time to nonpersistence, 140 days).  The primary outcome, death and cardiovascular event occurred respectively in 11.6, 11.2 and 0.8 percent of patients in the dabigatran group during a mean follow-up of 533 days, and in 8.6, 8.5 and 0.5 percent of those in the rivaroxaban group during a mean follow-up of 273 days. [Heart 2017;doi:10.1136/heartjnl-2016-310672]

Multivariable Cox proportional hazards model showed that nonpersistence was associated with a 76- and 89-percent increase in the risk of composite of stroke/TIA/death among dabigatran and rivaroxaban users, respectively (p<0.0001 for both). The risk of stroke/TIA events was also higher among patients nonpersistent to dabigatran (HR, 3.75; 2.59 to 5.43; p<0.0001) and rivaroxaban (HR, 6.25; 3.37 to 11.58; p<0.0001) than among those who were persistent. These associations were maintained on sensitivity analysis.

Among the factors associated with nonpersistence, male sex was the only one that emerged as significant in the dabigatran group. In the rivaroxaban group on the other hand, male sex, urban residence (vs rural), no prior warfarin use, no history of prior stroke/TIA and internist (vs a general practitioner prescriber) all factored into nonpersistence.

The findings are in line with previous studies reporting that nonpersistence rates are much higher in clinical practice than in the clinical trial setting, ranging from 19 to 42 percent with rivaroxaban and from 23 to 49 percent with dabigatran, researchers noted. [J Thromb Haemost 2015;13:495–504; Circ Cardiovasc Qual Outcomes 2013;6:567–74; Eur J Clin Pharmacol 2016;72:329–38; J Am Heart Assoc 2016;5:e003074]

They pointed out that in the current study, outcomes were only attributed to patients in the nonpersistent group after they became nonpersistent as follow-up for outcomes started at the time of nonpersistence to dabigatran/rivaroxaban and continued until the outcome was reached or the end of the study period.

Noting the worryingly high rate of dabigatran and rivaroxaban nonpersistence along with the associated increase in the risk of stroke, researchers emphasized the need for increased awareness of the potential for nonpersistence by clinicians and closer monitoring by anticoagulation clinics and pharmacists in the prevention of premature treatment discontinuation and the resulting deleterious outcomes.

“In clinical practice, close monitoring is not mandated by guidelines for NOACs… Without close monitoring and follow-up appointments, as is the norm with warfarin, patients taking NOACs in clinical practice may not actively seek an appointment with their healthcare provider to discuss medication intolerance and side effects, which may lead to drug nonpersistence,” they continued.

“The readily available structure of anticoagulation clinics that was established for monitoring warfarin therapy may provide a suitable mechanism for enhanced monitoring of the novel oral anticoagulants with the goal to improve adherence,” they said.

The study might be limited by the reliance on prescription claims to measure nonpersistence with dabigatran and rivaroxaban, a longer follow-up period for persistent vs nonpersistent patients, and the lack of information on aspirin use.

“Future studies should be conducted to determine actual barriers to dabigatran and rivaroxaban adherence,” researchers said.

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Most Read Articles
11 days ago
Increased serum levels of C-X-C motif chemokine (CXCL)-11, CXCL-9, CXCL-10 and interferon (IFN)-γ are associated with clinical manifestations of adult-onset Still’s disease (AOSD), reports a new study.
3 days ago
At a recent lunch symposium during the 14th Annual Scientific Meeting of the Malaysian Society of Hypertension, Dr Chow Yok Wai spoke on the importance of patient adherence in the management of hypertension, highlighting the role of combination therapy in improving treatment outcomes.
5 days ago
Myopia is associated with depressive symptoms in Chinese adults, a new population-based study shows.
5 days ago
Chronic obstructive pulmonary disease (COPD) is currently the 10th commonest cause of death in Singapore, with a disease burden of 5.9 percent according to a 2015 population-based survey (EPIC-Asia survey) in Singapore. Pearl Toh spoke with Dr Augustine Tee, chief and senior consultant of the Department of Respiratory and Critical Care Medicine at Changi General Hospital (CGH) in Singapore, on how COPD is often underdetected in the primary care population as symptoms are not specific and diagnosis requires a combination of clinical risk factors, symptoms and spirometry testing.