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Fanaroff, A. C., Clare, R., Pieper, K. S., Mahaffey, K. W., Melloni, C., Green, J. B., . . . Lopes, R. D. (2019). Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials. Circulation, 139(7), 863-873
Open this publication in new window or tab >>Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 7, p. 863-873Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient-and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term followup, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.

Keywords
clinical trial, cause of death, death, follow-up studies, quality control
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-378677 (URN)10.1161/CIRCULATIONAHA.118.037202 (DOI)000458410000008 ()30586739 (PubMedID)
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-03-12Bibliographically approved
Hijazi, Z., Oldgren, J., Lindbäck, J., Alexander, J. H., Connolly, S. J., Eikelboom, J. W., . . . Wallentin, L. (2018). A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. European Heart Journal, 39(6), 477-485
Open this publication in new window or tab >>A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 6, p. 477-485Article in journal (Refereed) Published
Abstract [en]

Aims: In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers.

Methods and results: The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score.

Conclusion: A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
Atrial fibrillation, Biomarkers, Mortality, NOAC, Oral anticoagulation, Risk score
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-348121 (URN)10.1093/eurheartj/ehx584 (DOI)000424876100015 ()29069359 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RB13-0197Swedish Heart Lung Foundation, 20090183
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2019-01-23Bibliographically approved
Guimarães, P. O., Leonardi, S., Huang, Z., Wallentin, L., de Werf, F. V., Aylward, P. E., . . . Tricoci, P. (2018). Clinical features and outcomes of patients with type 2 myocardial infarction: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial. American Heart Journal, 196, 28-35
Open this publication in new window or tab >>Clinical features and outcomes of patients with type 2 myocardial infarction: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial
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2018 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 196, p. 28-35Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Type 2 myocardial infarction (MI) is characterized by an imbalance between myocardial blood supply and demand, leading to myocardial ischemia without coronary plaque rupture, but its diagnosis is challenging.

METHODS: In the TRACER trial, patients with non-ST-segment elevation acute coronary syndromes were included. We aimed to describe provoking factors, cardiac biomarker profiles, treatment patterns, and clinical outcomes of patients with type 2 MIs. MI events during trial follow-up were adjudicated by an independent clinical events classification committee (CEC) and were classified according to the Third Universal Definition of MI. Using available source documents retrieved as part of the CEC process, we performed a retrospective chart abstraction to collect details on the type 2 MIs. Cox regression models were used to explore the association between MI type (type 1 or type 2) and cardiovascular death.

RESULTS: Overall, 10.3% (n=1327) of TRACER participants had a total of 1579 adjudicated MIs during a median follow-up of 502 days (25th and 75th percentiles [IQR] 349-667). Of all MIs, 5.2% (n=82) were CEC-adjudicated type 2 MIs, occurring in 76 patients. The incidence of type 2 MI was higher in the first month following randomization, after which the distribution became more scattered. The most frequent potential provoking factors for type 2 MIs were tachyarrhythmias (38.2%), anemia/bleeding (21.1%), hypotension/shock (14.5%), and hypertensive emergencies (11.8%). Overall, 36.3% had a troponin increase >10× the upper limit of normal. Coronary angiography was performed in 22.4% (n=17) of patients during hospitalizations due to type 2 MIs. The hazard of cardiovascular death was numerically higher following type 2 MI (vs. no MI, adj. HR 11.82, 95% CI 5.71-24.46; P<.0001) than that of type 1 MI (vs. no MI, adj. HR 8.90, 95% CI 6.93-11.43; P<.0001).

CONCLUSIONS: Type 2 MIs were more prevalent in the first month after ACS, were characterized by the presence of triggers and infrequent use of an invasive strategy, and were associated with a high risk of death. Further efforts are needed to better define the role and implications of type 2 MI in both clinical practice and research.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342889 (URN)10.1016/j.ahj.2017.10.007 (DOI)000424518000005 ()29421012 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-03-08Bibliographically approved
Pol, T., Held, C., Westerbergh, J., Lindbäck, J., Alexander, J. H., Alings, M., . . . Hijazi, Z. (2018). Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(3), Article ID e007444.
Open this publication in new window or tab >>Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial
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2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 3, article id e007444Article in journal (Refereed) Published
Abstract [en]

BackgroundDyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation. Methods and ResultsUsing data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14884 atrial fibrillation patients. Median length of follow-up was 1.9years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81; P<0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome (P=0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both P values 0.2448). ConclusionsIn patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation. Clinical Trial RegistrationURL: . Unique identifier: NCT00412984.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
atrial fibrillation, biomarkers, cardiovascular disease, cerebrovascular disease, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-351017 (URN)10.1161/JAHA.117.007444 (DOI)000426643800035 ()
Funder
Swedish Heart Lung Foundation, 20090183
Available from: 2018-05-24 Created: 2018-05-24 Last updated: 2019-01-23Bibliographically approved
Tricoci, P., Neely, M., Whitley, M. J., Edelstein, L. C., Simon, L. M., Shaw, C., . . . Bray, P. F. (2018). Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome: Analysis from the TRACER trial. Blood Cells, Molecules & Diseases, 72, 37-43
Open this publication in new window or tab >>Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome: Analysis from the TRACER trial
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2018 (English)In: Blood Cells, Molecules & Diseases, ISSN 1079-9796, E-ISSN 1096-0961, Vol. 72, p. 37-43Article in journal (Refereed) Published
Abstract [en]

Variation in platelet response to thrombin may affect the safety and efficacy of PAR antagonism. The Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the protease-activated receptor (PAR) 4 gene is associated with higher platelet aggregation compared to the Ala120 variant. We investigated the relationship between the rs773902 SNP with major bleeding and ischemic events, safety, and efficacy of PAR1 inhibition in 6177 NSTE ACS patients in the TRACER trial. There was a lower rate of GUSTO moderate/severe bleeding in patients with the Thr120 variant. The difference was driven by a lower rate in the smaller homozygous group (recessive model, HR 0.13 [0.02-0.92] P= 0.042). No significant differences were observed in the ischemic outcomes. The excess in bleeding observed with PAR1 inhibition was attenuated in patients with the Thr120 variant, but the interactions were not statistically significant. In summary, lower major bleeding rates were observed in the overall TRACER cohort with the hyperreactive PAR4 Thr120 variant. The increase in bleeding with vorapaxar was attenuated with the Thr120 variant, but we could not demonstrate an interaction with PAR1 inhibition. These findings warrant further exploration, including those of African ancestry where the A allele (Thr120) frequency is similar to 65%.

Keywords
Platelets, PAR1, PAR4, Bleeding, Pharmacogenetics
National Category
Cardiac and Cardiovascular Systems Hematology
Identifiers
urn:nbn:se:uu:diva-363094 (URN)10.1016/j.bcmd.2018.07.004 (DOI)000441057600008 ()30055940 (PubMedID)
Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2018-10-16Bibliographically approved
Dagenais, G. R., Jung, H., Lonn, E., Bogaty, P. M., Dehghan, M., Held, C., . . . Yusuf, S. (2018). Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(15), Article ID e008918.
Open this publication in new window or tab >>Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial
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2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 15, article id e008918Article in journal (Refereed) Published
Abstract [en]

Background-It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. Methods and Results-In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with >= 2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73-1.00). Rosuvastatin reduced CVD events in participants with >= 2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62-0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61-1.01). Consistent results were observed with combination therapy (>= 2 factors: HR: 0.74; 95% CI, 0.57-0.97; <2 factors: HR: 0.61; 95% CI, 0.43-0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61-1.00). Conclusions-Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
antihypertensive agent, statin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-372904 (URN)10.1161/JAHA.118.008918 (DOI)000452701900014 ()30033433 (PubMedID)
Funder
AstraZeneca
Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-01-11Bibliographically approved
Norlund, F., Lissåker, C., Wallert, J., Held, C. & Olsson, E. M. .. (2018). Factors associated with emotional distress in patients with myocardial infarction: Results from the SWEDEHEART registry. European Journal of Preventive Cardiology, 25(9), 910-920
Open this publication in new window or tab >>Factors associated with emotional distress in patients with myocardial infarction: Results from the SWEDEHEART registry
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2018 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 9, p. 910-920Article in journal (Refereed) Published
Abstract [en]

Background: Emotional distress, symptoms of depression and anxiety, is common among patients after a myocardial infarction (MI), and is associated with an increased risk of cardiovascular morbidity. Real world population data on factors associated with emotional distress in MI patients are scarce. The aim was to determine factors associated with incident emotional distress two and 12 months post MI respectively, and with persistent emotional distress, versus remittent, in patients <75 years old.

Design: This was a registry-based observational study.

Methods: Data from the national SWEDEHEART registry on 27,267 consecutive patients with a first-time MI, followed up at two and 12 months post MI ( n = 22,911), were included in the analyses. Emotional distress was assessed with the EuroQol-5D questionnaire. Several candidate sociodemographic and clinical factors were analysed for their association with emotional distress in multivariate models.

Results: Symptoms of emotional distress were prevalent in 38% and 33% at two and 12 months post MI respectively. At both time-points, previous depression and/or anxiety, readmission for new cardiovascular event, female gender, younger age, born outside the neighbouring Nordic countries, smoking and being neither employed nor retired showed the strongest associations with emotional distress. Other factors related to medical history, the MI and its care or were only modestly associated with emotional distress. Persistent emotional distress was associated with younger age, female gender, smoking and being born outside of the Nordic countries.

Conclusion: Previous depression/anxiety, female gender, younger age, smoking, born outside of the Nordic countries, neither employed nor retired and readmission due to cardiovascular events were strongly associated with emotional distress post MI. These factors may be of relevance in tailoring rehabilitation programmes.

Keywords
Depression, anxiety, myocardial infarction, psychosocial
National Category
Psychology Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-355492 (URN)10.1177/2047487318770510 (DOI)000434701900005 ()29692223 (PubMedID)
Funder
Swedish Research CouncilU‐Care: Better Psychosocial Care at Lower Cost? Evidence-based assessment and Psychosocial Care via Internet, a Swedish ExampleSwedish Heart Lung Foundation
Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-08-30Bibliographically approved
Norlund, F., Wallin, E., Olsson, E., Wallert, J., Burell, G., von Essen, L. & Held, C. (2018). Internet-based Cognitive Behavior Therapy for Symptoms of Depression and Anxiety among Patients with a Recent Myocardial Infarction: The U-CARE Heart Randomized Trial. Journal of Medical Internet Research, 20(3), Article ID e88.
Open this publication in new window or tab >>Internet-based Cognitive Behavior Therapy for Symptoms of Depression and Anxiety among Patients with a Recent Myocardial Infarction: The U-CARE Heart Randomized Trial
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2018 (English)In: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 20, no 3, article id e88Article in journal (Refereed) Published
Abstract [en]

Background: Symptoms of depression and anxiety are common after a myocardial infarction (MI). Internet-based cognitivebehavioral therapy (iCBT) has shown good results in other patient groups.

Objective: The aim of this study was to evaluate the effectiveness of an iCBT treatment to reduce self-reported symptoms ofdepression and anxiety among patients with a recent MI.

Methods: In total, 3928 patients were screened for eligibility in 25 Swedish hospitals. Of these, 239 patients (33.5%, 80/239women, mean age 60 years) with a recent MI and symptoms of depression or anxiety were randomly allocated to a therapist-guided,14-week iCBT treatment (n=117), or treatment as usual (TAU; n=122). The iCBT treatment was designed for post-MI patients.The primary outcome was the total score of the Hospital Anxiety and Depression Scale (HADS) 14 weeks post baseline, assessedover the internet. Treatment effect was evaluated according to the intention-to-treat principle, with multiple imputations. For themain analysis, a pooled treatment effect was estimated, controlling for age, sex, and baseline HADS.

Results: There was a reduction in HADS scores over time in the total study sample (mean delta=−5.1, P<.001) but no differencebetween the study groups at follow-up (beta=−0.47, 95% CI −1.95 to 1.00, P=.53). Treatment adherence was low. A total of46.2% (54/117) of the iCBT group did not complete the introductory module.

Conclusions: iCBT treatment for an MI population did not result in lower levels of symptoms of depression or anxiety comparedwith TAU. Low treatment adherence might have influenced the result.

Trial Registration: ClinicalTrials.gov NCT01504191; https://clinicaltrials.gov/ct2/show/NCT01504191 (Archived at Webciteat http://www.webcitation.org/6xWWSEQ22)

National Category
Psychology Cardiac and Cardiovascular Systems
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-336209 (URN)10.2196/jmir.9710 (DOI)000428245500002 ()25873137 (PubMedID)
Funder
Swedish Research Council, dnr 2009-1093Swedish Heart Lung Foundation, dnr E 148/11Forte, Swedish Research Council for Health, Working Life and Welfare, dnr 2014-4947Vårdal Foundation, dnr 2014-0114
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2018-07-24Bibliographically approved
Vinereanu, D., Wang, A., Mulder, H., Lopes, R. D., Jansky, P., Lewis, B. S., . . . Alexander, J. H. (2018). Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease. Heart, 104(15), 1292-1299
Open this publication in new window or tab >>Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease
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2018 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 104, no 15, p. 1292-1299Article in journal (Refereed) Published
Abstract [en]

Objective: To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.

Methods: There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.

Results: Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.

Conclusions; In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363951 (URN)10.1136/heartjnl-2017-312272 (DOI)000442379200014 ()29352007 (PubMedID)
Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2019-01-23Bibliographically approved
Wallert, J., Gustafson, E., Held, C., Madison, G., Norlund, F., von Essen, L. & Olsson, E. (2018). Predicting Adherence to Internet-Delivered Psychotherapy for Symptoms of Depression and Anxiety After Myocardial Infarction: Machine Learning Insights From the U-CARE Heart Randomized Controlled Trial. Journal of Medical Internet Research, 20(10), Article ID e10754.
Open this publication in new window or tab >>Predicting Adherence to Internet-Delivered Psychotherapy for Symptoms of Depression and Anxiety After Myocardial Infarction: Machine Learning Insights From the U-CARE Heart Randomized Controlled Trial
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2018 (English)In: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 20, no 10, article id e10754Article in journal (Refereed) Published
Abstract [en]

Background: Low adherence to recommended treatments is a multifactorial problem for patients in rehabilitation after myocardial infarction (MI). In a nationwide trial of internet-delivered cognitive behavior therapy (iCBT) for the high-risk subgroup of patients with MI also reporting symptoms of anxiety, depression, or both (MI-ANXDEP), adherence was low. Since low adherence to psychotherapy leads to a waste of therapeutic resources and risky treatment abortion in MI-ANXDEP patients, identifying early predictors for adherence is potentially valuable for effective targeted care.

Objectives: The goal of the research was to use supervised machine learning to investigate both established and novel predictors for iCBT adherence in MI-ANXDEP patients.

Methods: Data were from 90 MI-ANXDEP patients recruited from 25 hospitals in Sweden and randomized to treatment in the iCBT trial Uppsala University Psychosocial Care Programme (U-CARE) Heart study. Time point of prediction was at completion of the first homework assignment. Adherence was defined as having completed more than 2 homework assignments within the 14-week treatment period. A supervised machine learning procedure was applied to identify the most potent predictors for adherence available at the first treatment session from a range of demographic, clinical, psychometric, and linguistic predictors. The internal binary classifier was a random forest model within a 3×10–fold cross-validated recursive feature elimination (RFE) resampling which selected the final predictor subset that best differentiated adherers versus nonadherers.

Results: Patient mean age was 58.4 years (SD 9.4), 62% (56/90) were men, and 48% (43/90) were adherent. Out of the 34 potential predictors for adherence, RFE selected an optimal subset of 56% (19/34; Accuracy 0.64, 95% CI 0.61-0.68, P<.001). The strongest predictors for adherence were, in order of importance, (1) self-assessed cardiac-related fear, (2) sex, and (3) the number of words the patient used to answer the first homework assignment.

Conclusions: For developing and testing effective iCBT interventions, investigating factors that predict adherence is important. Adherence to iCBT for MI-ANXDEP patients in the U-CARE Heart trial was best predicted by cardiac-related fear and sex, consistent with previous research, but also by novel linguistic predictors from written patient behavior which conceivably indicate verbal ability or therapeutic alliance. Future research should investigate potential causal mechanisms and seek to determine what underlying constructs the linguistic predictors tap into. Whether these findings replicate for other interventions outside of Sweden, in larger samples, and for patients with other conditions who are offered iCBT should also be investigated.

Place, publisher, year, edition, pages
Air University Press, 2018
Keywords
Applied predictive modeling, cardiac rehabilitation, linguistics, supervised machine learning, recursive feature elimination, treatment adherence and compliance, Web-based interventions
National Category
Cardiac and Cardiovascular Systems Health Care Service and Management, Health Policy and Services and Health Economy Applied Psychology
Research subject
Health Care Research; Psychology
Identifiers
urn:nbn:se:uu:diva-357964 (URN)10.2196/10754 (DOI)30305255 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2014-4947Vårdal Foundation, 2014-0114U‐Care: Better Psychosocial Care at Lower Cost? Evidence-based assessment and Psychosocial Care via Internet, a Swedish Example, 2009-1093
Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2018-12-03Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9402-7404

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