Table 2. Characteristics of studies of pharmacist interventions for anticoagulation in atrial fibrillation.
Author (study name)×, year, country Study setting (n), study design Intervention/controlaSample sizebAge (median [IQR], or mean ± SD)cProportion of females, n (%) Description of intervention and control (where applicable) Main outcomes of intervention
Quality of warfarin therapy (TTR)
Wang, 2021, China44 Hospital (1), cohort study a57/208
b67.1 ± 10.9/70.4 ± 9.5
c31 (54.4%)/116 (55.8%)
Physician-pharmacist atrial fibrillation warfarin clinic, joint determination of INR target, drug dosage, treatment course, date of next visit. Pharmacist delivered patient education, assessment of TTR and INR at follow-up, dose adjustments as needed vs. general clinic (control) Significantly higher proportion of participants achieved a TTR ≥60% (intervention 73.7% vs. usual care 47.1%, p=0.002).
Marcattoπ, 2021, Brazil37 Hospital (1), cohort study a262
Pharmacist-led warfarin management for atrial fibrillation patients with TTR <50%, 12-week programme (education, dispensing, INR monitoring, dose adjustment, adherence/adverse event assessment). Pharmacist visits once weekly for 4 weeks, then according to INR monitoring. After week 12, medical team provide care without pharmacist presence
Significant difference in basal, 12-week and one year mean TTR within low-, medium- and high- warfarin adherence groups (low: 15.8% ± 17.4 vs. 35.9% ± 19.9 vs. 46.7% ± 20.8, p <0.001; medium: 11.7% ± 15.9 vs. 49.0% ± 23.5 vs. 51.7 ± 20.9, p <0.001; high: 13.7% ± 15.8 vs. 61.4% ± 21.5 vs. 60.8% ± 22.6, p<0.001).
Liang, 2019, China36 Hospital (1), randomised controlled trial a77/75
b60.1 ± 16.3/62.5 ± 14.5
c36 (46.8%)/31 (41.3%)
Pharmacist-led warfarin education and follow-up service (two phone calls day 30 and 90 post-discharge) vs. usual care (control) No significant difference in TTR (intervention 35.9% vs. usual care 29.5%, p=0.203)
Phelps, 2018, USA39 Non-profit integrated healthcare delivery system (1), before- and-after study a4764/3641
b74.6 ± 10.1/73.9 ± 10.6
c2626 (55.1%)/1948 (53.5%)
Pharmacist-led AMS with efforts to improve warfarin therapy for atrial fibrillation patients, specifically TTR vs. pharmacist-led AMS before efforts were made to improve warfarin therapy (control)
Significantly higher TTR after efforts were made as part of the pharmacist-led AMS (70.5% vs. 63.4%, p <0.001)
Kose, 2018, Japan30 Hospital (1), cohort study a16/23
b71.8 ± 2.2/ 72.3 ± 1.8
c7 (43.8%)/4 (17.4%)
Pharmacist and physician vs. physician only (control) guidance on warfarin treatment for atrial fibrillation patients with chronic kidney disease TTR (defined as PT-INR 1.6-2.6) significantly higher in pharmacist and physician group vs. physician only group (76.8% ± 15.6 vs. 55.9% ± 25.1, p= 0.005)
An, 2017, Japan20 Hospital (1), cohort study c25/32
d70 [64-76.5]/72 [66.3-76.8]
e13 (52%)/9 (28.1%)
Pharmacist (confirmation of drug-drug interactions, monitoring bleeding/PT-INR, dose adjustment recommendations, patient education - lifestyle precautions, warfarin-food interactions) and physician (oral instructions with lifestyle guidance generally omitted) management of atrial fibrillation patients with HF vs. physician only management (control) TTR (defined as PT-INR 1.6-2.6) significantly higher in pharmacist and physician group vs. physician only group (73.8% [61.4-93.4] vs. 59.8% [44.2- 77.4], p=0.017)
Aidit, 2017, Malaysia18 Hospital (1), before- and- after study a106/126
b66.11 ± 10.81 (all participants)
c80 (53%) (all participants)
Pharmacist and physician-led WMTAC for atrial fibrillation patients. Pharmacists responsible for patient education/counselling and implementation of a treatment protocol, recommendations made for dose adjustments/continuation of warfarin therapy vs. physician-led WMTAC with referral to pharmacist only when necessary (control) No significant difference in TTR between pharmacist and physician-led WMTAC vs. physician-led WMTAC (63.97% ± 19.41 vs, 59.25% ± 20.74, p=0.120)
Health outcomes
Wang, 2021, China44 Hospital (1), cohort study a57/208
b67.1 ± 10.9/70.4 ± 9.5
c31 (54.4%)/116 (55.8%)
See Wang 2021, Quality of warfarin therapy (TTR) No significant difference in thromboembolic (intervention 5.3% vs. control 5.3%, p=1.000) or bleeding events (intervention 3.5% vs. control 4.3%, p=1.000)
Li, 2020, China35 Hospital (1), cohort study a179/202
b76.3 ± 7.8/75.2 ± 7.1
c69 (38.5%)/80 (39.6%)
Remote pharmacist-led management of atrial fibrillation patients taking rivaroxaban. Education, drug administration and observation of drug interactions, weekly adverse event monitoring vs. usual care by cardiologists or primary care providers (control) No significant difference in thrombosis, heart failure, left atrial dilation. Significant reduction in incidence of gastrointestinal bleeding (intervention 6.1% vs. control 12.4%, p=0.038), skin ecchymosis (intervention 0.6% vs. control 4.5%, p=0.018)
Jones, 2020, USA27 Academic Healthcare System (1), cohort study a90/370
b68.9 ± 11/67.1 ± 12
c34 (37.8%)/141 (38.1%)
Pharmacist-led AMS for atrial fibrillation patients on NOACs. Initial patient education, phone calls (discuss stroke or bleeding concerns, adherence and provide reminders about required blood tests) or chart reviews vs. other providers - neurologists, cardiologists and primary care providers (control) No significant difference in the composite endpoint of thromboembolism, bleeding, and all-cause mortality between intervention vs. control (HR 1.25, 95% CI 0.70–2.24)
Kirwan, 2020, Canada29 Hospital emergency departments (2), cohort study a177
b70 [61-78]
Implementation of a pathway (SAFE) developed by pharmacists and physicians for patients with new atrial fibrillationdiagnoses (step 1: assessment of contraindications to OAC; step 2: stroke risk assessment with CHADS65; step 3: OAC dosing if indicated). Pathway triggered referral to atrial fibrillation clinic, letter for family physician and follow-up call from pharmacist 65/73 (89%) participants reached 90 days follow-up, one report of gastrointestinal bleeding in participant taking OAC, and one report of stroke in participant who refused OAC
Phelps, 2018, USA39 Non-profit integrated healthcare delivery system (1), before- and- after study a4764/3641
b74.6 ± 10.1/73.9 ± 10.6
c2626 (55.1%)/1948 (53.5%)
See Phelps 2018, Quality of warfarin therapy (TTR)
Significantly lower odds of the composite endpoint of clinically-relevant bleeding, thromboembolism and all-cause mortality associated with pharmacist-led anticoagulant management (adjusted OR 0.69, 95% CI 0.54-0.87)
An, 2017, USA19 Non-profit, integrated healthcare delivery organisation (1), comprised of hospitals (14), outpatient facilities (>200), and a centralised laboratory (1), cohort study a32074
b72.2 ± 10.7
c13645 (42.5%)
Pharmacist-led anticoagulation clinic for atrial fibrillation patients on warfarin (approximately weekly for first three months of treatment and every three weeks after six months). Pharmacists responsible for monitoring, dose adjustment and reversal, triage of related adverse events, drug interaction interventions, telephone counselling No significant difference in stroke or systemic embolism event rates between patients with TTR <65% who received frequent pharmacist interventions (≥24 times per year) and patients with TTR <65% who received less frequent interventions (1.88 vs. 1.54 per 100 person-years, respectively, p=0.780)
Lee, 2013, USA33 Outpatient clinic (1), before- and- after study a20/48*
b78 [72–83]/72 [67–81]
c0 (0%)/1 (2%)
Pharmacist anticoagulation clinic for dabigatran (patient education on adherence, tolerance issues, storage and refill at initial consultation). Follow-up at two weeks, one month and three months vs. usual care (control) No significant difference in frequency of minor (p=0.148) or major bleeding events (p=0.516) between pharmacist anticoagulation clinic for dabigatran and usual care
OAC prescribing
Sandhu (PIAAF Rx), study ongoing, Canada62 Community pharmacy (), randomised controlled trial a370 (estimate)
Community pharmacist initiates/adjusts OAC therapy in atrial fibrillation patients vs. enhanced usual care -community pharmacist refers atrial fibrillation patients to physician for OAC therapy (control) Proportion of participants receiving optimal OAC therapy (pending, study ongoing)
Brouillette, 2021, Canada46 Multidisciplinary heart failure clinic (1), general outpatient clinic (1), cohort study a307
MDT follow-up of cardiologists, nurses and pharmacists for atrial fibrillation patients vs. cardiologist-only follow-up (control) Inappropriate anticoagulant use less likely with MDT follow-up (8% vs. 22%). Prescription of VKA in NOAC-eligible patients and incorrect NOAC dosing were the most common reasons for inappropriate use
Khalil, 2021, Australia28 Hospital (1), before- and- after study a65/61
b72.78 ± (males), 75.03 ± (females)/75.30 ± (males), 74.60 ± (females)
c29 (44.6%)/30 (49.1%)
One-to-one education with pharmacist during admission new atrial fibrillation patients, provision of atrial fibrillation brochure to promote shared decision making about OAC therapy vs. usual care provided pre-intervention (control) Significant improvement in the appropriateness of OAC therapy (intervention 92% vs. control 36%, p <0.001)
Schwab, 2021, USA40 Hospital (1), cohort study a146/99
b73.6 ± 14.7/75.2 ± 12.6
c77 (52.7%)/51 (51.5%)
Emergency physicians, pharmacists and electrophysiologists collaborating in shared decision-making model; emergency physician identifies atrial fibrillation patients using ECG, referral to electrophysiologist when atrial fibrillation confirmed, pharmacist determines appropriate OAC, provides medication, arranges post-discharge clinic with electrophysiologist/ cardiologist vs. usual care (control) Significant increase in proportion of atrial fibrillation patients discharged on OAC (87.8% intervention vs. 62.3% control, P ≤0.001)
Wang§, 2019, USA45 AMS clinics (14), randomised controlled trial a1727§
Pharmacist assessment of appropriateness of initiating OAC in atrial fibrillation patients identified with CHA2DS2-VASc score ≥2 and no OAC prescription within 12 months, escalation to primary care provider as needed vs. usual care (control) 432/1727 (25%) participants potentially eligible for OAC. After pharmacist screening, 75/432 (17%) escalated to the primary care provider. No significant increase in proportion of OAC prescriptions (intervention 4.1% vs. control 4.0%, p=0.860)
Mensah, 2019, USA38 , cohort study a489
Pharmacist review of patient records to confirm documentation supporting absence of OAC in patients with atrial fibrillation /atrial flutter. Pharmacist contact with physician to request review to initiate OAC or document reason for no treatment 349/489 (71.4%) patients had warfarin initiated or clear documentation to explain reason for the absence of OAC therapy after pharmacist review
Leef, 2019, USA34 Veterans Health Administration (1), cohort study a5060
b69 ± 10
c96 (1.9%)
AMS for new atrial fibrillation patients started on NOACs, generally led by pharmacists
Improvement in correct NOAC dosing when compared to other fee-for-service non-integrated systems. 4735/5060 (93.6%) new atrial fibrillation patients prescribed rivaroxaban or dabigatran at the correct dose, 86/5060 (1.7%) overdosed and 239/5060 (4.7%) under-dosed
Durand, 2018, UK25 General practices (20), before- and- after study a501
Pharmacist identification of atrial fibrillation patients not on OAC or on antiplatelet monotherapy using patient records and APL- AF software, review of medical records to confirm atrial fibrillation diagnosis, blood results and patient characteristics with initiation of OAC therapy (warfarin or NOACs) when indicated vs. usual care provided pre-intervention (control) Significant increase in proportion of atrial fibrillation patients prescribed OAC from 62% to 80%, p <0.001
Brown, 2017, UK22 Outpatient clinics (), before- and- after study a†
Pharmacist-led virtual clinics with GPs to identify atrial fibrillation patients with a CHA2DS2VASc score ≥2 not anticoagulated vs. usual care provided pre-intervention (control) Increased prescription of anticoagulation for atrial fibrillation patients in two CCGs from 73% (pre-intervention) to 83% (post-intervention), and from 72% to 78%
Virdee, 2017, UK43 General Practices (15), cross-sectional study a497
b75.5 ± 11.9
Pharmacist treatment recommendations made to GP for atrial fibrillation patients with CHA2DS2-VASc score ≥1/≥2 (male/female) and no anticoagulant prescription 202/497 participants (40.6%) suitable for anticoagulation, 103/202 (51%) commenced on anticoagulant (76/202 refused, 16/202 failed to attend, 7 commenced treatment in secondary care), 85/103 (83%) switched from antiplatelet to anticoagulant
Dowling, 2016, UK24 Outpatient clinic (1), cohort study a87
b76.9 ±
c46 (52.9%)
Pharmacist-led anticoagulant review clinic (weekly, four-hour clinic for six months) targeted at atrial fibrillation patients on VKA with TTR <65% 65/87 (74.7%) switched from VKA to NOAC, 63/87 continued on NOAC at two-week follow-up, 1/87 had VKA discontinued (haemorrhagic risk outweighed benefit), 21/87 (24.1%) remained on VKA
Larock, 2014, Belgium31 Hospital (1), cross-sectional study a69
b74 [45-89]
c26 (38%)
Pharmacist assessment of dabigatran and rivaroxaban prescribing using Medication Appropriateness Index tool adapted for NOAC prescribing with recommendations made to physicians 34/69 (49%) inappropriate criteria for treatment, 48 pharmacist interventions, 94% accepted by physicians
Jackson, 2011, Australia26 Hospital (1), before- and- after study a134/394
b79 ± /75 ±
c84 (63%)/180 (45%)
Pharmacist stroke risk assessment in atrial fibrillation patients, antithrombotic therapy recommendations to physicians vs. usual care provided pre-intervention (control) Significant increase in warfarin use from 43% to 58% p=0.050, significant decrease in aspirin use from 48% to 39%, p=0.040 from admission to discharge in intervention group, no significant change in antithrombotic use from admission to discharge in usual care
Touchette, 2007, USA42 Hospital (1), before- and- after study a154/98
b79.7 ± 10.2/77.8 ± 10.1
c76 (49.4%)/57 (58.2%)
Pharmacist review of antithrombotic prescribing in atrial fibrillation patients, assessment of bleeding risk factors, interacting medicines, direct patient interview, treatment recommendations made to physicians vs. usual care provided pre-intervention (control)
No significant difference in antithrombotic use (70.8% intervention vs. 67.3% control, p=0.580), significant difference in proportion of patients with antithrombotic discharge plan (88.3% intervention vs. 73.5% control, P <0.01), significantly higher odds of planned or actual warfarin use with intervention (aOR 2.46, 95% CI 1.63-3.74)
Bajorek, 2005, Australia21 Hospital (1), cohort study a218
b85.2 ± 6.2
Pharmacist identification of atrial fibrillation patients, consultation with patients, caregivers and MDT to obtain information for application of evidence-based algorithm to determine appropriate antithrombotic, discussion with clinical team at ward rounds/case conferences before final treatment decisions made 78/218 (35.8%) had changes made to antithrombotic prescribed pre-intervention (at admission); 60/78 (76.9%) treatment upgrade (no therapy/antiplatelet to anticoagulant), significant overall increase in antithrombotic use pre-intervention vs. post-intervention (at discharge), 59.6% vs 81.2%, p <0.001
Burkiewicz, 2004, USA23 Outpatient clinics (2), cohort a131/47
b71.7 ± 11.3/74.7 ± 11.5
c66(50.4%)/24 (51.1%)
Ambulatory care clinic (delivered by cardiologists and primary care physicians) for atrial fibrillation patients with access to a pharmacist‐staffed AMS vs. ambulatory care clinic without access (control) Significant difference in warfarin use between clinic with access to pharmacist-staffed AMS vs. clinic without access (77.9% vs. 61.7%, p=0.030), access to pharmacist-staffed AMS was an independent predictor of warfarin use (adjusted OR 2.19, 95% CI 1.05-4.56)
Medication adherence, knowledge and patient satisfaction
Khalil, 2021, Australia28 Hospital (1), before- and- after study a65/61
b72.78 ± (males), 75.03 ± (females)/75.30 ± (males), 74.60 ± (females)
c29 (44.6%)/30 (49.1%)
See Khalil 2021, OAC prescribing
Significant improvement in patient satisfaction measured using a standard satisfaction survey based on a Likert scale (intervention 68% vs. control 25%, p <0.001)
Sun, 2021, China17 Hospital (1), randomised controlled trial a100/99
b75.9 ± 9.0/75.8 ± 9.1
c45 (45%)/46 (46.5%)
Pharmacist implementation of evidence-based pharmaceutical care model. Pharmacists consider patients’ preferences, search and evaluate literature, provide objective suggestions to hospitalised atrial fibrillation patients taking rivaroxaban vs. implementation of a general pharmaceutical care model (control) Satisfaction (14.6 ± 0.9 vs.13.8 ± 1.0, p <0.01) and cognition scores (22.6 ±2.2 vs 20.8 ± 3.0, p <0.01) measured using a questionnaire designed by the researchers significantly higher in patients in intervention group
Leblanc, 2017, Canada32 , cohort study a338
Pharmacist delivered education and counselling to atrial fibrillation patients taking NOACs
Increased patient knowledge (assessed using five questions) of atrial fibrillation and NOAC use from 3.7/5 (baseline) to 4.3/5 (4 month follow-up), increased medication adherence from 93% (baseline) to 98% (4 month follow-up), P <0.001
Shore, 2015, USA41 Veterans Health Administration sites (67), mixed-method study a4863
Pharmacist review of dabigatran prescriptions for atrial fibrillation patients, patient education, adverse event and adherence monitoring Pharmacist patient education had no effect on dabigatran adherence (adjusted RR 0.94, 95% CI 0.83-1.06), significant association between pharmacist-led monitoring on dabigatran adherence (adjusted RR 1.25, 95% CI 1.11–1.41)
Lee, 2013, USA33 Outpatient clinic (1), before- and- after study a20/48*
b78 [72–83]/72 [67–81]
c0 (0%)/1 (2%)
See Lee 2013, Health otucomes No effect on mean medication possession ratio (intervention 93.1% vs. control 88.3%), no effect on the proportion of participants achieving a medication possession ratio ≥80% (intervention 25% vs. usual care 10%, p=0.160)
AMS, anticoagulant management service; APL-AF, Active Patient Link – Atrial Fibrillation; CCG, clinical commissioning group; CHADS65 score, Canadian algorithm which recommends anticoagulation for most people aged 65 years old and for younger patients with congestive heart failure, hypertension, age, diabetes, stroke/transient ischemic attack score of 1; CHA2DS2-VASc score, score of 1 point each for congestive heart failure, hypertension, female, age 65-74 years, diabetes mellitus, vascular disease and 2 points for previous stroke/transient ischaemic attack/thromboembolism and age ≥75 years; CI, confidence interval; ECG, electrocardiogram; GP, general practitioner; HF, heart failure; HR, hazard ratio; MDT, multidisciplinary team; NOAC, non-vitamin K antagonist oral anticoagulant; OAC, oral anticoagulant; OR, odds ratio; PIAAF-RX, The Improving Stroke Prevention in Atrial Fibrillation Through Pharmacist Prescribing study; PT-INR, prothrombin time – international normalised ratio; RR, relative risk; TTR, time in therapeutic range; VKA, vitamin K antagonist; WMTAC, warfarin medication therapy adherence clinic