Integrated Management of Atrial Fibrillation in Primary Care Demonstrates 45% Reduction in All-Cause Mortality Compared to Usual Care in Elderly Patients

Sabawoon Mirwais, M.D.
By Sabawoon Mirwais, M.D. on

In a recent Dutch study, published in European Heart Journalintegrated care for elderly atrial fibrillation (AF) patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care.

The Study

A cluster randomized, pragmatic, non-inferiority trial in primary care, the ALL-IN trial, registered at the Netherlands Trial Register (NL5407), sought to determine whether integrated care for AF extended in primary care is non-inferior compared to usual care performed by cardiologists and anticoagulation clinics. Twenty six participating practices were randomized between October 2015 and January 2017. Fifteen practices were randomized to the integrated care intervention and 11 to usual care.

The integrated care intervention comprised of (i) quarterly AF check-ups by trained nurses in primary care, with additional focus on possible interfering comorbidities, (ii) monitoring of anticoagulation therapy in primary care, including international normalized ratio (INR) measurements performed by the intervention practice in those treated with a vitamin K antagonist (VKA), special attention to drug compliance, and monitoring of kidney function in patients using a non-vitamin K antagonist oral anticoagulant (NOAC), and (iii) easy-access consultation of anticoagulation clinics and/or cardiologists. Practice nurses in the intervention practices received appropriate training on the signs and symptoms of AF and heart failure, rate and rhythm contol, and an explanation of the AF guidelines. The investigators also organized 3 meetings throughout the 2-year follow-up period for both practice nurses and general practitioners (GPs) aiming to share experiences and to provide additional education. The usual care varied per patient, but for most of the patients, it included a once yearly consultation of a cardiologist or AF nurse at the outpatient cardiology department of the affiliated hospital. For the patients discharged from care by their cardiologist, the GP was the point of contact in case of signs or symptoms related to AF or other conditions. For patients using a VKA, anticoagulation clinics affiliated to the local hospital performed the INR measurements and created the dosage calendar, yet without involvement of the GP. For patients using a NOAC, no structured control was in place in the control group.

The primary outcome was all-cause mortality during 2 years follow-up. Secondary outcomes were cardiovascular and non-cardiovascular mortality, cardiovascular and non-cardiovascular hospitalization, major adverse cardiac events (MACE), stroke, major bleeding, clinically relevant non-major bleeding (CRNMB), health-related quality of life (HrQoL), and cost-effectiveness.

Inclusion criteria consisted of documented AF and age ≥ 65 years. Exclusion criteria consisted of (i) presence of an internal cardioverter-defibrillator or a cardiac resynchronization therapy device; (ii) cardioversion, cardiac ablation, or cardiac surgery < 3 months prior to inclusion or being planned; (iii) heart valve surgery in the past; (iv) a rheumatic mitral valve stenosis; (v) pulmonary vein isolation in the past or being planned; (vi) being legally incapable of providing informed consent; (vii) a life expectancy shorter than 3 months; and (viii) participation in another randomized trial on AF.

In the intervention arm, 527 out of 941 eligible AF patients aged ≥ 65 years provided informed consent to undergo the intervention. These 527 patients were compared with 713 AF patients in the control arm receiving usual care. Median age was 77 (interquartile range 72 – 83) years. The all-cause mortality rate was 3.5 per 100 patient-years in the intervention arm vs. 6.7 per 100 patient-years in the control arm [adjusted hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.37 – 0.82]. For non-cardiovascular mortality, the adjusted HR was 0.47 (95% CI 0.27 – 0.82). For other adverse events, no statistically significant differences were observed. All practices completed the follow-up period of 2 years. The uptake and persistence of performing the intervention were high; there was no drop-out of intervention practices and 93% of the patients who started the intervention completed it.


This is the first study demonstrating the effectiveness of structured AF management in primary care. The results can be generalized to the majority of AF patients and the proposed intervention can be implemented in more rural areas. The low number of patients lost to follow-up and the high compliance rate in the intervention arm are also promising aspects of the study.


Inherent to using cluster randomized design with interventions delivered on an individual patient level, selection bias could have occurred. The investigators did not have information on echocardiographic parameters, NT-proBNP levels, and type of AF (persistent, permanent, or paroxysmal). This information could help in understanding why and in whom integrated AF care is most beneficial. Finally, the substitution of care from cardiologist to primary care was less than expected (41% of intervention patients and 48% of the control patients had routine cardiologist control visits during follow-up); hinting at the possibility that many intervention patients received extra care due to the intervention itself.

Questions to Ask

An interesting question at this point would be which aspect of the intervention mostly correlates with the reduction in mortality. While the authors do have an interesting hypothesis vis-à-vis the unprecedented findings, further research is needed to explore the specific components of integrated AF care. A thorough cost-effectiveness analysis is also warranted, which the authors have pledged to publish separately.

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