Management of Atrial fibriLLation INcluding tailoring of anticoagulation in patients from primary care - ALL-IN

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a
prevalence of 1-2% with rates increasing with age. The majority (about 70%) of
these AF patients is aged 65 years and over, with about 20% even aged above 85
years. Managing these elderly patients with AF is complex, requiring an
integral management and partnerships between primary and secondary care, as
well thrombosis services. It is complex for two important reasons.
First, ischemic stroke is the most important complication in these patients.
Anticoagulation - either a vitamin K antagonist (VKA) or a novel oral
anticoagulant (NOAC) - is highly effective to reduce this stroke risk, but is
also known for the inherent bleeding complications. Thus, careful tailoring
anticoagulation treatment is needed in individual patients based on an
individualized risk of developing an ischemic stroke as well the patients*
tolerance and adherence to anticoagulants use. AF patients are at high risk of
hospital admissions, bleeding, and strokes are both related to AF. It has been
hypothesized that at least part of these hospital admissions are preventable,
given that current care implies that multiple health professionals all are only
responsible for a part of patient*s treatment.
Second, AF is part of a broader cardiovascular disease spectrum. As such, most
elderly AF patients have co-morbidities: e.g. congestive heart failure,
hypertension, and ischemic heart disease, and also non-cardiovascular diseases,
such as diabetes, COPD, cognitive- or renal impairment. Thus, besides stroke
prevention in AF, this multi-morbidity determines the treatment (goals) and
reasons for hospital referral and admissions in (often) frail older patients
with AF.
Although for more than a decade integral disease management already exists with
nurses supervised by GPs for patients with diabetes type 2, hypertension,
coronary artery disease, and stroke - all with good results. Such structured
care performed by Practice Nurses (PN) in primary care for patients with AF is
currently non-existent.
The hypothesis of this study proposal is whether an integral AF management in
primary care - including case-management for anticoagulation as well as
appropriate attention given to all cardiac and non-cardiac co-morbidities -
improves patient care for elderly AF patients, as compared to usual care.
The research question is:
Will integral AF management - focusing on optimizing anticoagulation and
optimizing attention for co-morbidity in AF - in a primary care setting reduce
all-cause deaths and hospitalizations (and thus healthcare costs) in elderly AF
patients (aged 65+), as compared to usual care?

To evaluate whether integral AF treatment in primary care is non-inferior in
terms of reducing all-cause mortality (primary outcome) and specific cardiac
mortality and hospitalization and non-cardiac hospitalization (secondary
outcomes), as compared to usual (fragmented) care.

Integral AF management is defined as
• Case-management of tailored anticoagulant management: INR measurements
performed by practice nurses in primary care for those patients prescribed VKA,
or quarterly check-ups in patients treated with NOAC, emphasizing treatment
compliance. Anticoagulation management thus is performed in primary care, in
close collaboration with cardiologists and the (local) Thrombosis Service.
• Adequate care for AF-related comorbidities and poly-pharmacy by trained
practice nurses and general practitioners.
• Easy-access to cardiologists care and a thrombosis expertise centre for
general practitioners where needed for complex AF cases, or in case referral is
needed to secondary care. All AF patients still currently cared for in
secondary care are referred back to primary care where appropriate and possible
(depending on national and international guidelines).

This is a prospective randomized pragmatic trial in elderly patients who are
treated for AF, performed in primary care.

The intervention under study in this proposal is aimed at participating primary
care practices. All AF patients not having one of the aforementioned exclusion
criteria and registered within this practice are the target group. At the start
of the project (before randomization) the general practitioner and practice
nurse of each practice will determine the number of AF patients potentially
eligible for this study, according to the in- and exclusion criteria. These
patients are defined as the study patients. Next, after randomization, each
practice is visited to validate the list of study patients and to facilitate
optimizing treatment with anticoagulation, according to the CHA2DS2-VASc score.
The CHA2DS2-VASc score (cardiac failure, hypertension, age>=75 (doubled),
diabetes, stroke (doubled) - vascular disease, age 65-74 and sex category
(female)) is advocated to estimate the risk of stroke in AF patients and
subsequently drives the need for (possible) anticoagulation: no anticoagulation
at a CHA2DS2-VASc score of 0 or 1, and prescription of VKA or a NOAC in those
with a score of 2 or more. Hereto, a list is made of all women aged 65 years or
over and all men aged 75 years or over (CHA2DS2-VASc score of 2) who do not
receive anticoagulation yet, as well as a list of all men aged between 65 and
75 years. The general practitioner is asked to check the indication for
anticoagulation and to consider starting anticoagulant treatment (i.e. VKA or a
NOAC) if the CHA2DS2-VASc score is 2 or more. This list is given to all
participating general practitioners. Also, all general practitioners are
offered the possibility to consider starting a NOAC in patients with a VKA,
according to local guidance on NOAC treatment, in close collaboration with
cardiologists. Nevertheless, the decision to change anticoagulation treatment
is left to the discretion of the treating general practitioner and/or
cardiologist.
When a primary care practice is randomised for the intervention, the
investigational treatment in this study - integral AF management - will be
performed by the practice nurse (PN), supervised by the general practitioner.
Integral AF management encompasses a) case-management of anticoagulation in
primary care, b) chronic care for AF and its related comorbidities, and c)
availability of an easy-access consultation possibility by cardiologists and
thrombosis experts if needed.
Integral AF management is explained in more detail below.

A: Case-management of anticoagulation in primary care: Study patients in the
intervention group treated with a VKA are offered tailored anticoagulation
monitoring by the PN with INR measurements in the primary care practice (using
point-of-care INR measuring) and dosage advice is received using the online
portal of the Thrombosis Service. If needed, home-visits are made. The PN
provides important information for the Thrombosis Service to take into account
when calculating the dosage advice, based on the actual health status, recent
medication or treatment changes. If patients have anticoagulation questions or
problems, the PN can determine the actual INR and give treatment advice or
consult the Expert Center of the TS, whatever is deemed appropriate given the
clinical context of the INR derailment. In addition, to ensure the safety of
this transferring of INR measurements from the Thrombosis Service to primary
care, the PN will be trained and peer supervision will be organized, guided by
the Expert Center. For patients treated with a NOAC, the NOAC therapy will be
part of the quarterly check-ups mentioned in section B.
B: Chronic AF care including assessment and proper attention to all AF-related
co-morbidity: Quarterly, the PN and once yearly the general practitioner
evaluates the patients* health condition and treatment (including compliance)
for AF according to the guidelines of the Dutch General Practitioners (NHG
Standaard Atriumfibrilleren). The NHG Standaard CardioVasculair Risico
Management -CVRM protocol is followed to optimize treatment of other
cardiovascular diseases (hypertension, heart failure, status after MI and
stroke, lipid lowering if needed, etc.) and the NHG Standaard Diabetes Mellitus
is followed if patients have diabetes. The PN coordinates the health programs
if other caregivers are involved to warrant integral care.
C: Easy access consultation: If needed, the participating general practitioner
will have access to an easy to use consultation possibility for either the
cardiologist or a thrombosis expert, through telephone or e-mail. If needed,
prompt referral to secondary care is applied. Patients who used to have regular
check-ups for atrial fibrillation by the cardiologist will visit their
cardiologist for a closing visit, after which the patient will be referred back
to primary care. Regular check-ups by the cardiologist for cardiac conditions
other than atrial fibrillation will be continued when necessary and
appropriate. These appointments will be complementary to the integral AF
management provided by the practice nurse and general practitioner.

It is expected that this study will result in a lower mortality, bleeding- and
thrombotic occurrences. Yet, similar or perhaps potentially higher compared to
those treated with usual care, patients undergoing the intervention are at risk
of these outcomes. We anticipate this potential higher risk to be minimal
however. Finally, patients need to fill in *quality of life* questionnaires.