Table 1.
Summary of controlled trials and observational studies
| Author, y of publicationref | Data collection period | Treatment/population | Study details | PRO assessment | Sample size | Outcomes measured | Main findings of the study |
|---|---|---|---|---|---|---|---|
| Patients with atrial fibrillation | |||||||
| Monz et al. 201323 | December 2005–December 2007 |
Treatment: Dabigatran vs dose adjusted warfarin population: For nonvalvular AF Mean age: 71.5 y Female: 36.4% |
Design: RCT Subgroup of RE‐LY population RE‐LY = prospective, randomized open‐label, blinded end‐point evaluation Setting: 44 countries and 951 clinical centres |
Patient‐reported HRQoL using EQ‐5D utility and visual analogue scale scores, assessed at baseline, 3 and 12 months | 1435 patients (497 in dabigatran 110 mg BD, 485 dabigatran 150 mg BD group and 453 warfarin group) | Changes in HRQoL over time 5 questions on 5 dimensions of health (mobility, self‐care, usual; activities, pain/discomfort, anxiety/depression) and 3 levels of response |
HRQoL: No statistically significant difference between dabigatran groups or warfarin groups. Utility weighted scores for dabigatran 150 mg BD ranged from 0.805 to 0.811 for dabigatran 110 mg BD and did not change over the 1‐y observation period. No difference between dabigatran and warfarin group except dabigatran 150 mg at 3 months. None of the in‐groups or between‐group analyses were significant |
| Hohnloser et al. 201524 | October 2012–September 2013 |
Treatment: Rivaroxaban vs standard therapy for cardioversion Population: Patients with AF requiring cardioversion Age range: 18–65 y Female: 52.7% |
Design: RCT post hoc study of X‐VERT trial, Setting: 7 countries USA, UK Canada, Netherlands, France, Germany and Italy |
Patient‐reported treatment satisfaction using user TSQM Ver II, completed after 42 days of treatment | 705 patients completed the questionnaire |
11 items, 4 subscales Convenience, effectiveness, global satisfaction and side effects based on Likert scales |
Satisfaction: Rivaroxaban group reported increased score for convenience (81.74 vs 65.78), effectiveness (39.41 vs 32.95) and global satisfaction (82.07 vs 66.74), P < .0001. |
| Coleman et al. 201625 |
Treatment: Rivaroxaban for stroke prevention Population: Patients with nonvalvular AF prescribed rivaroxaban Mean age: 71 y Female: 36.3% |
Design: Nonrandomized controlled trial Xantus ACTS substudy Prospective international noninterventional phase 4 study, Setting: 308 investigational sites in 21 countries |
Patient‐reported treatment satisfaction using ACTS implemented at baseline and 3 months after switch | 1291 patients with prior warfarin treatment switched to rivaroxaban | 12‐item burden scale (max 60 points) and 3‐item benefits scale (max 15 points) |
Satisfaction: Baseline ACTS burden and benefit scores 50.51 and 10.30 respectively, scores improved after 3 months to 54.5 and 11.4, respectively |
|
| Koretsune et al. 201726 | September 2015–October 2016 |
Treatment: Patients switched from warfarin to apixaban population: Patients with nonvalvular AF Mean age: 76 y Female: 37.9% |
Design: RCT prospective short‐term multicentre single‐arm observational study AGAIN study Setting: 149 institutions in Japan |
Patient‐reported treatment satisfaction using ACTS, implemented before switch and after 12 weeks of treatment with apixaban | 697 patients switched to apixaban | 12‐item burden scale (max 60 points) and 3‐item benefits scale (max 15 points) | Satisfaction: No significant changes in ACTS benefit scores (10.5 vs 10.4) but significant changes in ACTS burden scores vs baseline (55.6 vs 49.7, P < .0001) |
| Alegret et al., 201427 | 1 February–30 June 2012 |
Treatment: On VKA or NOAC Population: Patients with AF undergoing electrical cardioversion Mean age: 62 y Female: 19% |
Design: Prospective study Patients included in the CARDIOVERSE study Setting: Conducted in 67 hospitals in Spain |
Patient‐reported HRQoL in patients on oral anticoagulants using Sawicki questionnaire, assessed at baseline and 6 months |
416 patients: 351 in VKA group and 65 in DOAC (59 on dabigatran and 5 on rivaroxaban) group. At 6 months 215 in VKA group and 37 in NOAC group completed the questionnaire |
32 items grouped in 5 dimensions. Patients score on scale of 1–6 to determine their treatment related quality of life | HRQoL: No significant differences seen at baseline between the groups. At baseline, general treatment satisfaction score was significantly lower in the NOAC group (better HRQoL). Global score was also lower, indicating better HRQoL in NOAC group (10.3 vs 9.6). No significant differences seen at 6 months between the groups. |
| Hanon et al., 201628 | April 2013–June 2014 |
Treatment: Patients previously treated with warfarin and switched to rivaroxaban Population: Nonvalvular AF patients Mean age: 74.8 y Female: 37% |
Design: Prospective, observational study Setting: French multicentre |
Patient‐reported treatment satisfaction using ACTS, administered at baseline, 1, 3 and 6 months | 405 patients switched to rivaroxaban | A validated 15‐item patient‐reported scale including 12‐item ACTS burdens scale and 3 item ACTS benefits scale | Satisfaction: At 3 months, statistically significant patient satisfaction with rivaroxaban compared with VKA warfarin. Mean ACTS burden score (46.5 vs 54.9, P < .001) and benefit scale (10.4 vs 10.9, P < .001) between rivaroxaban and VKA |
| Marquez‐Contreras et al. 201629 | May 2013–April 2015 |
Treatment: Patients on rivaroxaban Population: Patients with nonvalvular AF Mean age: 75 y Female: 50.3% |
Design: Observational, prospective, multicentre, longitudinal study Setting: Conducted in 160 primary and specialty care centres in Spain |
Patient‐reported quality of life using Sawicki questionnaire, administered at baseline and at 6 and 12 months | 370 included in the study | Sawicki questionnaire = 32 items grouped in 5 dimensions. General treatment satisfaction, self‐efficacy, strained social network, daily hassles and distress | HRQoL: Global compliance was 84.1% and 80.3% at 6 and 12 months respectively. Average QoL rating was 112.85 in noncompliant and 111.80 in the compliant group (p > 0.05). After 12 months 124.67 in noncompliant group and 83.47 in the compliant group (P < .0001) showing a significantly improved QoL. |
| Keita et al., 201730 | July 2014 to July 2015 |
Treatment: Patients prescribed warfarin or switched to DOAC or initiated on DOAC treatment Population: VTE patients Mean age: 60.4 y Female: 46% |
Design: Observational descriptive study Setting: multicentre in France |
Patient‐reported adherence, satisfaction and QoL using Morisky medication adherence scale, MMAS‐8, EQ‐5D, perception of anticoagulation questionnaire part 2, administered after 3 months treatment and 6 months treatment | 100 patients 50 in warfarin group and 50 in DOAC group | EQ‐5D questionnaire (5 dimensions, mobility, autonomy, usual activities, pain/discomfort, anxiety/depression) with 3 response levels. PACT‐Q2 to assess treatment satisfaction: 3 domains, practical aspects satisfactions and adherence. MMAS‐8: 8‐item questionnaire |
HRQoL: VKA patients reported more negative experience than DOAC group in EQ‐5d questionnaire. No significant difference in overall quality of life in favour of DOAC group (71 vs 65, P < .063). Satisfaction: Satisfaction with PACT‐Q2: >90% of patients were satisfied with their VKA or DOAC treatment. Adherence: Adherence with MMAS‐8 7.2 in VKA group vs 7.7 in DOAC group greater adherence in DOAC group especially after 6 months treatment. |
| Contreras Muruaga et al. 201731 | September 2014–March 2015 |
Treatment: Population: Patients with nonvalvular AF Mean age: 75 y Female: 44.2% |
Design: Observational cross‐sectional study Setting: 63 neurology departments in Spain |
Patient‐reported satisfaction, QoL and perceptions of VKA vs DOACs (only QoL included) |
1337 patients: 587 on DOAC, 750 on VKA |
EQ‐5D 3‐level questionnaire and visual acuity score |
HRQoL: Mean EQ‐5D 3 L score was 75.9 Patients taking VKA with longer time in therapeutic range were more satisfied. DOAC = 76.26, VKA = 75.05: Showing no significant difference in HRQoL. HRQoL for all 3 DOACs were comparable |
| Stephenson et al. 201832 | October 2011–June 2014 |
Treatment: Patients prescribed warfarin, dabigatran, rivaroxaban or apixaban Population: Patients with nonvalvular AF Mean age: 65.6 y Female: 39.4% |
Design: Hybrid observational study Setting: Conducted in 14 institutions in the USA |
Patient‐reported adherence using Morisky medication adherence scale MMAS‐8 Duke anticoagulation treatment scale, administered at baseline, and at 4, 8 and 12 months |
675 patients 271 in warfarin group 266 dabigatran group 128 rivaroxaban group 10 in apixaban group |
Validated patient‐reported tool. Measures medication taking behaviours and explores circumstances influencing adherence. Scores 0–8 DASS score 4 points to measure QoL and satisfaction among OAC treatment |
Adherence: Mean MMAS scores were similar among all 4 groups in the initial and follow up surveys Satisfaction: DASS scores were lower for dabigatran and rivaroxaban cohort indicating greater treatment satisfaction |
| de Caterina et al., 201833 | 2012–2013 |
Treatment: On stable VKA or switched to NOAC (rivaroxaban, dabigatran or apixaban) Population: Patients with AF Mean age: 72 y Female: 37% |
Design: Prospective study PREFER in AF registry sub study Setting: Conducted in 7 European countries |
Patient‐reported QoL and satisfaction using PACT‐ Q2 and EQ‐5D‐5 L questionnaires, administered at baseline and at 1 y follow‐up | 2950 patients completed the questionnaires, excluded patients stable on NOAC. 2102 patients on stable treatment with VKA, 213 patients switched from VKA to NOAC | PACT Q2 questions about satisfaction EQ‐5D‐5 L questions investigate several aspects of QoL. | Satisfaction: Switched patients more often reported bruising or bleeding, dissatisfaction with treatment, mobility problems and anxiety/depression traits with VKA that may have influenced the switch to NOAC. |
| Koretsune et al., 201834 | April 2012 |
Treatment: Rivaroxaban in patients previously on warfarin Population: Nonvalvular AF patients Mean age: 73.6 y Female: 35.5% |
Design: Postmarketing surveillance study of a prospective study Setting: 124 sites in Japan |
Patient‐reported treatment satisfaction ACTS and TSQM Ver II, administered at baseline and at 3 and 6 months | 665 patients included in the study |
ACTS burden and benefits TSQM Ver II |
Satisfaction: Statistically significant improved TSQM scores in the rivaroxaban group at month 3 and 6 compared to baseline in all 4 domains (P < .001). Significantly (P < .001) less burden at 3 months (54.6) and month 6 (54.5) vs baseline (51.0), and benefit remained stable in the rivaroxaban group |
| Larochelle et al., 201835 | February 2013–December 2014 |
Treatment: Patients newly prescribed an oral anticoagulant (either warfarin or DOAC, apixaban, rivaroxaban or dabigatran) Population: Patient with nonvalvular AF Mean age: 71.35 y Female: ~60% |
Design: Prospective observational study Setting: Hospitals in Canada |
Patients expectations and satisfaction with oral anticoagulation treatment using PACT Q1 and PACT Q2 questionnaires, administered before treatment and at 3 and 6 months postdischarge | 159 patients included (71 on warfarin and 88 on DOAC, mainly rivaroxaban) |
PACT Q = perception of anticoagulant treatment questionnaire Q1 = 7 questions on patient expectations Q2 = 20 questions on treatment convenience, burden of disease and treatment and anticoagulant treatment satisfaction. |
Expectations: No significant differences in treatment expectations, patients prescribed warfarin had a slightly higher expectation of having side effects. Satisfaction: Convenience scores were similar at 3 months but much higher in DOAC group at 6 months (86.29 vs 90.97, P < .05). Satisfaction scores were similar between groups. |
| Benzimra et al., 201836 | June 2013–November 2015 |
Treatment: Patients receiving oral anticoagulants VKA/DOAC (dabigatran, rivaroxaban or apixaban), or switched treatments Population: Patient with AF Mean age: 74.3 y Female: 41% |
Design: Real‐life observational descriptive cross‐sectional study Setting: Various recruitment sites in France |
Quality of life, treatment satisfaction and adherence using 3 validated questionnaires‐ EQ‐5D 3‐level visual analogue scale, perception of anticoagulation treatment questionnaire PACT‐Q2, 8 item Morisky scale medication adherence scale MMAS‐8, administered once over the phone to patients for at least 3 months treatment | 200 patients (89 on VKA, 52 on DOAC, 50 switched to DOAC, 9 switched to VKA) |
EQ‐5D: 5 dimensions mobility, self‐care, usual activities, pain/discomfort and anxiety/depression. Score 0–100 PACT‐Q2 assess treatment satisfaction with anticoagulant assesses convenience, burden and satisfaction.
MMAS‐8 assesses adherence to therapy through 8 questions. |
HRQoL: HRQoL: EQ‐5D scores were similar in all groups but higher in the DOAC group. Overall QoL on the EQ‐5D visual analogue scale tended to be better in the DOAC group but this was not statistically significant. Satisfaction: Convenience and satisfaction scores were high in all 3 groups but significant difference in favour of the DOAC group (P < .001) Adherence: Adherence scores were high for all 3 groups with no significant difference between the groups. |
| Okumura et al. 201837 | September 2013 and December 2015 |
Treatment: Patients on anticoagulation (VKA/DOAC) Population: Patients with non valvular AF Mean age: 72 y Female: 22.6% |
Design: Substudy of SAKURA AF registry Questionnaire‐based prospective study Setting: 40 institutions in Japan |
Patients satisfaction with anticoagulant treatment using ACTS and TSQM Ver II, administered once |
1475 patients: 654 in DOAC group (241 dabigatran, 331 rivaroxaban and 1 edoxaban) in 821 warfarin group. 513 completed the ACTS questionnaire |
ACTS: 17‐item questionnaire to measure patient satisfaction addressing burden and benefits. The TSQM II covers 4 domains, effectiveness, side effects, convenience and global satisfaction. | Satisfaction: There were no significant differences in the TSQM II questionnaire between the groups. The ACTS burden scores were significantly higher for the DOAC group than the warfarin group showing greater satisfaction with treatment. |
| Fernandez et al., 201838 |
ALADIN Study: September 2014 to March 2015 ESPARTA Study: October 2015 to March 2016 |
Treatment: Patients prescribed VKA or DOAC Population: Patients with nonvalvular AF Mean age: 78.5 y Female: 48.95% |
Design: 2 different cross‐sectional studies combined (ALADIN and ESPARTA studies) Setting: Various departments in Spain |
Patient satisfaction with anticoagulant treatment using ACTS questionnaire, administered at regular single visit, patients on at least 3 months treatment |
ALADIN study: 472 patients ESPARTA study: 837 patients. 1309 patients in total, 902 VKA group ad 407 DOAC group |
ACTS is patient‐reported measure of satisfaction with anticoagulation.12 items that assess perceived burdens, 4 items to assess perceived benefits | Satisfaction: Overall satisfaction with oral anticoagulation was high. Patients taking DOACs showed a lower perceived burden with anticoagulation therapy (48.8 vs 53.1, P < .001). Perceived benefits were higher in DOAC group (11.06 vs 11.99, P < .001). |
| Obamiro et al., 201839 | Not specified |
Treatment: Prescribed oral anticoagulants Population: Patients with AF Age range: 18–>65 y Female: 68% |
Design: Secondary analysis of the Australian oral anticoagulation survey Setting: Conducted through online recruitment in Australia |
Predictors of adherence and patient related factors of adherence using Morisky medication adherence scale (MMAS‐8), anticoagulation knowledge tool and PACT Q1 and Q2 questionnaires |
386 patients (warfarin: 100 patients, apixaban: 121 patients, rivaroxaban: 123 patients, dabigatran: 42 patients) |
MMAS‐8 to assess levels of adherence. AKT to assess OAC knowledge and perception of anticoagulation treatment questionnaires assessing treatment expectation, global convenience and satisfaction. |
Adherence: No significant difference in adherence seen between patients taking warfarin and DOACs. Patients in the high adherence group showed a higher anticoagulation knowledge. Satisfaction: Satisfaction scores were greater in the medium adherence groups. |
| Patients with VTE (PE and DVT) | |||||||
| Bamber et al. 201340 | March 2007 to Sept 2009 |
Treatment: Rivaroxaban vs enoxaparin/warfarin for population: Patients with DVT Mean age: 56.8 y Female: 42.4% |
Design: RCT Substudy analysis of EINSTEIN DVT study Setting: Conducted in 7 countries (USA, UK, Canada, Netherlands, France, Germany and Italy) |
Patient‐reported treatment satisfaction using ACTS score, assessed at 12 months of treatment | 1472 patients | ACTS 15‐point score burden and benefits |
Satisfaction: Clinically significant reduction in ACTS burden (55.2 vs 52.6, P < .0001) and improvement in ACTS benefit (11.7 vs 11.5, P = .006) in rivaroxaban group (compared with warfarin) |
| Prins et al., 201441 | March 2007–March 2011 |
Treatment: Rivaroxaban vs standard therapy (enoxaparin/warfarin) Population: Patient with PE Mean age: 58 y Female: 44% |
Design: Sub analysis of EINSEIN PE study Setting: 7 countries USA, UK Canada, Netherlands, France, Germany and Italy |
Patient‐reported treatment satisfaction using ACTS and TSQM Ver II, assessed at 1, 2, 3, 6 and 12 months |
2397 patients (1200 in rivaroxaban arm and 1197 in enoxaparin/warfarin arm) |
ACTS 15‐point scale burden scale and benefit scale |
Satisfaction: Rivaroxaban group reported statistically significant increase in ACTS benefit (11.9 vs 11.4, P < .0001) and less ACTS burden (55.4 vs 51.9, P < .0001)
Statistically significant improved TSQM II scores in the rivaroxaban group P < .0001 for all 4 factors, effectiveness, side‐effects, convenience and global satisfaction |
| Carrothers et al., 201442 | May 2010 to December 2011 |
Treatment: Patients prescribed rivaroxaban Population: VTE prophylaxis following lower limb arthroplasty Mean age: 66 y Female: 61% |
Design: Prospective study Setting: single orthopaedic Centre in Canada |
Patient‐reported compliance using self‐administered questionnaire, administered 14 days postsurgery and 6 weeks after treatment at the follow‐up appointment | 2621 patients attended the 6‐week appointment | Yes/no questionnaire developed by the investigators to measure adherence/compliance, | Compliance: Majority of patients were compliant with rivaroxaban treatment (83%), noncompliance was associated with older age, lower body mass index and lower preoperative haemoglobin. |
| Patients with AF and VTE | |||||||
| Castellucci et al., 201543 | September 2012–September 2013 |
Treatment: Patients on oral anticoagulants (VKA, rivaroxaban, dabigatran and apixaban) Population: VTE and AF patients Mean age: 63 y Female: 42.7% |
Design: Cross‐sectional survey setting: Conducted in 1 anticoagulant clinic in Canada | Self‐reported anticoagulant adherence using 4 item Morisky score, administered once | 500 patients (367 on VKA, 130 on DOACS) | 4‐item Morisky adherence scale used | Adherence: Self‐reported adherence using the 4 item Morisky scale was 56.2% on VKA and 57.1% on DOAC. Adherence was similar in groups. |
ACTS, Anti‐Clot Treatment Scale; AF, atrial fibrillation; BD, twice a day; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; EQ‐5D, EuroQol 5D questionnaire (5 dimensions); HRQoL, health‐related quality of life; NOAC, new oral anticoagulant; QoL, quality of life; PACT, Perception of Anticoagulation Questionnaire; RCT, randomized controlled trial; TSQM Ver II, treatment satisfaction questionnaire for medication version II ; VKA, vitamin K antagonist; VTE, venous thromboembolism.