Long-term effects and predictors of change of internet-delivered cognitive behavioural therapy on cardiac anxiety in patients with non-cardiac chest pain: a randomized controlled trial.

BACKGROUND: Approximately half of patients who seek care at Emergency Departments due to chest pain are diagnosed with Non-Cardiac Chest Pain (NCCP). Concerns for heart disease and misinterpretation of the symptoms increase cardiac anxiety and have a negative impact on patients' lives. Psychological interventions such as internet-delivered cognitive behavioral therapy (iCBT) are effective in treating psychological conditions such as anxiety, by helping patients to learn how to manage chest pain. AIMS: To evaluate the effects of a nurse-led iCBT program on cardiac anxiety and secondary outcomes, as bodily sensations, depressive symptoms, health-related quality of life and chest pain frequency in patients with NCCP at 6- and 12-month follow-up, and to explore predictors that can have impact on the effects of the iCBT program on psychological distress. METHODS: A longitudinal study of a Randomized Controlled Trial (RCT) evaluating the long-term effects of an iCBT program (n = 54) in patients with NCCP, compared to psychoeducation (n = 55). The primary outcome, cardiac anxiety was measured using the Cardiac Anxiety Questionnaire (CAQ), and the secondary outcomes were measured with The Body Sensations Questionnaire (BSQ), Patient Health Questionnaire-9 (PHQ-9), The EuroQol Visual Analog Scale (EQ-VAS) and a self-developed question to measure chest pain frequency. All measurements were performed before and after the intervention, and 3, 6 and 12 months after the intervention. Linear mixed model was used to test between-group differences in primary and secondary outcomes and multiple regression analysis was used to explore factors that may have an impact on the treatment effect of iCBT on cardiac anxiety. RESULTS: A total of 85% (n = 93/109) participants completed the 12-month follow-up. Mixed model analysis showed no statistically significant interaction effect of time and group between the iCBT and psychoeducation groups regarding cardiac anxiety over the 12-month follow-up. However, there was a statistically significant interaction effect of time and group (p = .009) regarding chest pain frequency favouring the iCBT group. In addition, we found a group effect in health-related quality of life (p = .03) favouring the iCBT group. The regression analysis showed that higher avoidance scores at baseline were associated with improvement in cardiac anxiety at 12-month follow-up. CONCLUSIONS: Cardiac anxiety was reduced in patients with NCCP, but iCBT was not more effective than psychoeducation. Patients with a high tendency to avoid activities or situations that they believe could trigger cardiac symptoms may benefit more from psychological interventions targeting cardiac anxiety. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov NCT03336112 on 08/11/2017.

Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes.

BACKGROUND: The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS: We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS: We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], <1.3; P<0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P=0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P=0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3% vs. 0.1%, P=0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P<0.001). CONCLUSIONS: In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARE-TIMI 58 ClinicalTrials.gov number, NCT01730534 .).

The experience of participating in an internet-based cognitive behavioral therapy program among patients with cardiovascular disease and depression: a qualitative interview study.

BACKGROUND: Depression in conjunction with cardiovascular disease (CVD) is associated with worsening in CVD, higher mortality, and poorer quality of life. Despite the poor outcomes there is a treatment gap of depression in CVD patients. Recently we found that an Internet-based cognitive behavioral therapy (iCBT) tailored for CVD patients led to reduced symptoms of depression. However, we still have little knowledge about CVD patients' experiences of working with iCBT. The aim of this study was therefore to explore CVD patients' experiences of engaging in a tailored iCBT program. METHODS: A qualitative interview study using inductive thematic analysis. Data was obtained from 20 patients with CVD and depressive symptoms who had participated in a randomized controlled trial (RCT) evaluating the impact of a nine-week iCBT program on depression. RESULTS: Three main themes emerged: (1) Taking control of the disease, (2) Not just a walk in the park, and (3) Feeling a personal engagement with the iCBT program. The first theme included comments that the tailored program gave the patients a feeling of being active in the treatment process and helped them achieve changes in thoughts and behaviors necessary to take control of their CVD. The second theme showed that patients also experienced the program as demanding and emotionally challenging. However, it was viewed as helpful to challenge negative thinking about living with CVD and to change depressive thoughts. In the third theme patients reported that the structure inherent in the program, in the form of organizing their own health and the scheduled feedback from the therapist created a feeling of being seen as an individual. The feeling of being acknowledged as a person also made it easier to continuously work with the changes necessary to improve their health. CONCLUSIONS: Engaging in an iCBT program tailored for patients with CVD and depression was by the patients perceived as helpful in the treatment of depression. They experienced positive changes in emotions, thoughts, and behaviors which a result of learning to take control of their CVD, being confirmed and getting support. The patients considered working with the iCBT program as demanding and emotionally challenging, but necessary to achieve changes in emotions, thoughts, and behaviors.

The Effect of Internet-Delivered Cognitive Behavioral Therapy Versus Psychoeducation Only on Psychological Distress in Patients With Noncardiac Chest Pain: Randomized Controlled Trial.

BACKGROUND: Patients with recurrent episodes of noncardiac chest pain (NCCP) experience cardiac anxiety as they misinterpret the pain to be cardiac related and avoid physical activity that they think could threaten their lives. Psychological interventions, such as internet-delivered cognitive behavioral therapy (iCBT), targeting anxiety can be a feasible solution by supporting patients to learn how to perceive and handle their chest pain. OBJECTIVE: This study aims to evaluate the effects of a nurse-led iCBT program on cardiac anxiety and other patient-reported outcomes in patients with NCCP. METHODS: Patients with at least two health care consultations because of NCCP during the past 6 months, and who were experiencing cardiac anxiety (Cardiac Anxiety Questionnaire score ≥24), were randomized into 5 weeks of iCBT (n=54) or psychoeducation (n=55). Patients were aged 54 (SD 17) years versus 57 (SD 16) years and were mainly women (32/54, 59% vs 35/55, 64%). The iCBT program comprised psychoeducation, mindfulness, and exposure to physical activity, with weekly homework assignments. The primary outcome was cardiac anxiety. The secondary outcomes were fear of bodily sensations, depressive symptoms, health-related quality of life, and chest pain frequency. Intention-to-treat analysis was applied, and the patients were followed up for 3 months. Mixed model analysis was used to determine between-group differences in primary and secondary outcomes. RESULTS: No significant differences were found between the iCBT and psychoeducation groups regarding cardiac anxiety or any of the secondary outcomes in terms of the interaction effect of time and group over the 3-month follow-up. iCBT demonstrated a small effect size on cardiac anxiety (Cohen d=0.31). In the iCBT group, 36% (16/44) of patients reported a positive reliable change score (≥11 points on the Cardiac Anxiety Questionnaire), and thus an improvement in cardiac anxiety, compared with 27% of (13/48) patients in the psychoeducation group. Within-group analysis showed further significant improvement in cardiac anxiety (P=.04) at the 3-month follow-up compared with the 5-week follow-up in the iCBT group but not in the psychoeducation group. CONCLUSIONS: iCBT was not superior to psychoeducation in decreasing cardiac anxiety in patients with NCCP. However, iCBT tends to have better long-term effects on psychological distress, including cardiac anxiety, health-related quality of life, and NCCP frequency than psychoeducation. The effects need to be followed up to draw more reliable conclusions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03336112; https://www.clinicaltrials.gov/ct2/show/NCT03336112.

Healthcare use in patients with cardiovascular disease and depressive symptoms - The impact of a nurse-led internet-delivered cognitive behavioural therapy program. A secondary analysis of a RCT.

Background: Depressive symptoms in patients with cardiovascular disease (CVD) can lead to increased healthcare use. In a randomized controlled trial (ClinicalTrials.gov, NCT02778074), we reported that a 9-week internet-delivered cognitive behavioural therapy (iCBT) program (n = 72) compared to an online discussion forum (ODF) (n = 72) had moderate to large effect on depression in CVD outpatients. In this secondary analysis, we aimed to describe and compare the effect of iCBT compared to ODF regarding healthcare use and to identify factors impacting healthcare use in these groups. Methods: Data on healthcare use were retrieved from care data registries in five hospitals in Southeastern Sweden. Results: The year prior to intervention, the iCBT group had a mean of 31 outpatient clinic/primary care contacts per patient compared with 21 contacts the year after. The corresponding numbers for the ODF group were 37 and 25. The decrease was 32 % in both groups and did not differ significantly (p = 0.261 and p = 0.354) between the groups. Regarding hospital admissions, the iCBT group had 0.8 admissions per patient the year before and 0.6 the year after the intervention, a decrease by 25 %, whereas the ODF group had 1.1 and 0.6 admissions respectively, a decrease by 45 %. The difference was not statistically significant (p = 0.270 and p = 0.883) between the groups. Improvement in depressive symptoms post intervention were significantly (Beta = 0.459, p = 0.047) associated with a decrease in number of outpatient contacts in the iCBT group. In the ODF group, better mental health-related quality of life post intervention was significantly (Beta = -0.429, p = 0.045) associated with a decrease in number of hospital admissions. Conclusion: Reduced depressive symptom scores following intervention were associated with lower outpatient service use, but iCBT was not superior compared to ODF. This implicates that reducing depression in CVD patients, regardless of the type of internet-delivered intervention used, is important since it may reduce healthcare use in these patients.

Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trial.

BACKGROUND: In people with type 2 diabetes at high risk of cardiovascular or kidney disease, sodium-glucose co-transporter 2 (SGLT2) inhibitors consistently reduce the risk of hospitalisations for heart failure. Less is known about their effects on hospitalisation from any cause, especially in people with type 2 diabetes without atherosclerotic cardiovascular disease, which includes most of the global population of people with type 2 diabetes. We aimed to assess the effect of the SGLT2 inhibitor, dapagliflozin, on the risks of hospitalisations for any cause and for specific causes in people with type 2 diabetes with and without atherosclerotic cardiovascular disease. METHODS: The DECLARE-TIMI 58 trial was a double-blind, multicentre, randomised, placebo-controlled study. People with type 2 diabetes and either risk factors for or established atherosclerotic cardiovascular disease were randomly assigned (1:1) to receive oral dapagliflozin 10 mg or placebo once daily. In these post-hoc analyses, the effects of dapagliflozin on risks of first non-elective any-cause and cause-specific hospitalisation were assessed with Cox proportional hazards regression models overall and in the subset of participants without prevalent atherosclerotic cardiovascular disease. The risk of total (first plus subsequent) non-elective hospitalisations was assessed with Lin-Wei-Ying-Yang model. Investigator-reported System Organ Class terms were used to classify cause-specific hospitalisations. The trial is registered with ClinicalTrials.gov, NCT01730534. FINDINGS: Between April 25, 2013, and Sept 18, 2018, 17 160 people (6422 [37·4%] women, 10 738 [62·6%] men; mean age 63·9 years [SD 6·8]) were enrolled in the original trial, of whom 10186 (59·4%) had multiple risk factors for but did not have established atherosclerotic cardiovascular disease, and 6835 (39·8%) had both no evidence of atherosclerotic cardiovascular disease and low KDIGO risk. Over a median follow-up of 4·2 years (IQR 3·9-4·4), dapagliflozin was associated with a lower risk of first non-elective hospitalisation for any cause (2779 [32·4%] of 8582 people in the dapagliflozin group vs 3036 [35·4%] of 8578 people in the placebo group; hazard ratio [HR] 0·89 [95% CI 0·85-0·94]) and total (first plus subsequent) non-elective hospitalisations for any cause (risk ratio 0·92 [95% CI 0·86-0·97]). The association between dapagliflozin use and the risk of first non-elective hospitalisation for any cause was consistent in subgroups of participants with (HR 0·92 [95% CI 0·85-0·99] and without (0·87 [0·81-0·94]) atherosclerotic cardiovascular disease at baseline (p interaction=0·31). Compared with the placebo group, the dapagliflozin group had lower risk of first hospitalisations due to cardiac disorders (HR 0·91 [95% CI 0·84-1·00]), metabolism and nutrition disorders (0·73 [0·60-0·89]), renal and urinary disorders (0·61 [0·49-0·77]), and due to any other cause excluding these three causes (0·90 [0·85-0·96]). Treatment with dapagliflozin was also associated with a lower risk of hospitalisations due to musculoskeletal and connective tissue disorders (HR 0·81 [0·67-0·99]) and infections and infastations (HR 0·86 [0·78-0·96]). INTERPRETATION: Dapagliflozin reduced the risk of first and total non-elective hospitalisations for any cause in people with type 2 diabetes, regardless of the presence of atherosclerotic cardiovascular disease, including hospitalisations not directly attributed to cardiac, kidney, or metabolic causes. These findings might have implications on health-related quality of life for people with type 2 diabetes and on health-care costs attributable this condition. FUNDING: AstraZeneca.

Trajectories and associations between depression and physical activity in patients with cardiovascular disease during participation in an internet-based cognitive behavioural therapy programme.

BACKGROUND: There is a lack of knowledge about internet-based cognitive behavioural therapy in patients with cardiovascular disease, and its effects on depressive symptoms and physical activity. AIM: To examine trajectories of depressive symptoms and physical activity, and to explore if these trajectories are linked with the delivery of internet-based cognitive behavioural therapy. METHODS: A secondary-analysis of data collected in a randomised controlled trial that evaluated the effects of a 9-week internet-based cognitive behavioural therapy programme compared to an online discussion forum on depressive symptoms in cardiovascular disease patients. Data were collected at baseline, once weekly during the 9-week intervention period and at the 9-week follow-up. The Montgomery Åsberg depression rating scale - self-rating (MADRS-S) was used to measure depressive symptoms. Two modified items from the physical activity questionnaire measuring frequency and length of physical activity were merged to form a physical activity factor. RESULTS: After 2 weeks the internet-based cognitive behavioural therapy group had a temporary worsening in depressive symptoms. At 9-week follow-up, depressive symptoms (P<0.001) and physical activity (P=0.02) had improved more in the internet-based cognitive behavioural therapy group. Only in the internet-based cognitive behavioural therapy group, was a significant correlation (r=-0.39, P=0.002) between changes in depressive symptoms and changes in physical activity found. Structural equation analyses revealed that internet-based cognitive behavioural therapy decreased depressive symptoms, and that a decrease in depression, in turn, resulted in an increase in physical activity. CONCLUSIONS: Internet-based cognitive behavioural therapy was more effective than an online discussion forum to decrease depressive symptoms and increase physical activity. Importantly, a decrease in depressive symptoms needs to precede an increase in physical activity.

The impact of internet-based cognitive behavioral therapy and depressive symptoms on self-care behavior in patients with heart failure: A secondary analysis of a randomised controlled trial.

BACKGROUND: Patients with chronic heart failure may require treatment of depressive symptoms to improve self-care behaviour. OBJECTIVES: To investigate the impact of internet-based cognitive behavioral therapy (CBT) on self-care behaviour in heart failure patients, and to study the association between changes in depressive symptoms and changes in self-care behaviour. DESIGN: A secondary analysis of data collected in a pilot randomized controlled study. SETTING: 50 heart failure patients with depressive symptoms were recruited from four hospitals in Sweden. METHODS: Patients were randomized to nine weeks of internet-based CBT (n = 25) or to an active control group participating in an online discussion forum (n = 25). In week two and three, those in the internet-based CBT group worked with psychoeducation about heart failure and depression, emphasizing heart failure self-care. During the same weeks those in the on-line discussion forum specifically discussed heart failure self-care. Patient Health Questionnaire-9 was used to measure depressive symptoms at baseline and at the nine-week follow-up. The European Heart Failure Self-care Behaviour Scale-9 was used to measure self-care behaviour (i.e., the summary score and the subscales autonomous based, provider based and consulting behaviour) at baseline, and at the three-week and nine-week follow-ups. RESULTS: No significant differences were found in self-care between the patients in the internet-based CBT and the patients in the online discussion group at the three- and nine-week follow-up. Within-group analysis of the changes in the European Heart Failure Self-care Behaviour Scale showed that from baseline to week three, the summary score increased significantly for the online discussion group (p = 0.04), but not for the internet-based CBT group (p = 0.15). At the nine-week follow-up, these scores had decreased. Similarly, consulting behaviour improved at week three for the online discussion group (p = 0.04), but not for the internet-based CBT group (p = 0.22). Provider-based adherence at the nine-week follow-up had increased from baseline in the internet-based CBT group (p = 0.05) whereas it had decreased in the on-line discussion group. Improvement in symptoms of depression was significantly associated with improvement in autonomy-based self-care (r = 0.34, p = 0.03). CONCLUSION: Improvement in depressive symptoms was associated with improved autonomous-based self-care. ICBT for depression in HF may benefit aspects of self-care that are vital to improve symptoms and prognosis.

Implementing internet-delivered cognitive behavioural therapy for patients with cardiovascular disease and psychological distress: a scoping review.

BACKGROUND: Comorbid psychological distress (i.e. insomnia and depression) is experienced by 20-40% of patients with cardiovascular disease. This has a considerable impact on their health and quality of life, leading to frequent re-hospitalisations, higher healthcare costs and a shorter life expectancy. Internet-based cognitive behavioural therapy shows great potential for treating psychological distress in cardiovascular disease. Effective and feasible treatments can, however, only benefit patients if they are fully implemented in clinical care. AIM: This scoping review aimed to explore the literature for internet-based cognitive behavioural therapy in cardiovascular disease and for strategies to implement the intervention. METHODS: We searched electronic databases, journals and internet sources to find original studies about internet-based cognitive behavioural therapy in cardiovascular disease, adhering to scoping methodology guidelines. After identifying 267 titles, we screened 40 abstracts and chose 11 full-text articles for full-text screening. The results sections in four articles were searched for outcomes that related to the effectiveness and implementation of internet-based cognitive behavioural therapy by directed qualitative content analysis using an implementation framework. RESULTS: Three of the four articles fulfilling the inclusion criteria concerned internet-based cognitive behavioural therapy for treating mild to moderate depressive symptoms in cardiovascular disease, and none focused on insomnia. The studies showed evidence for the effectiveness of internet-based cognitive behavioural therapy, and/or described patient factors influencing clinical effectiveness. Our qualitative content analysis showed that many implementation aspects and stakeholder perspectives remain unexplored. CONCLUSIONS: Internet-based cognitive behavioural therapy promises to alleviate patient suffering in cardiovascular disease. There is, however, little research about internet-based cognitive behavioural therapy for cardiovascular disease, and about how this evidence-based intervention is implemented.

An Internet-Based Cognitive Behavioral Therapy Program Adapted to Patients With Cardiovascular Disease and Depression: Randomized Controlled Trial.

BACKGROUND: Depression is a common cause of reduced well-being and prognosis in patients with cardiovascular disease (CVD). However, there is a lack of effective intervention strategies targeting depression. OBJECTIVE: The study aimed to evaluate the effects of a nurse-delivered and adapted internet-based cognitive behavioral therapy (iCBT) program aimed at reducing depression in patients with CVD. METHODS: A randomized controlled trial was conducted. A total of 144 patients with CVD with at least mild depression (Patient Health Questionnaire-9 [PHQ-9] score ≥5) were randomized 1:1 to a 9-week program of iCBT (n=72) or an active control participating in a Web-based discussion forum (online discussion forum [ODF], n=72). The iCBT program, which included 7 modules, was adapted to fit patients with CVD. Nurses with an experience of CVD care provided feedback and a short introduction to cognitive behavioral therapy. The primary outcome, depression, was measured using PHQ-9. Secondary outcomes were depression measured using the Montgomery-Åsberg Depression Rating Scale-self-rating version (MADRS-S), health-related quality of life (HRQoL) measured using Short Form 12 (SF-12) survey and EuroQol Visual Analogue Scale (EQ-VAS), and the level of adherence. An intention-to-treat analysis with multiple imputations was used. Between-group differences in the primary and secondary outcomes were determined by the analysis of covariance, and a sensitivity analysis was performed using mixed models. RESULTS: Compared with ODF, iCBT had a significant and moderate treatment effect on the primary outcome depression (ie, PHQ-9; mean group difference=-2.34 [95% CI -3.58 to -1.10], P<.001, Cohen d=0.62). In the secondary outcomes, compared with ODF, iCBT had a significant and large effect on depression (ie, MADRS-S; P<.001, Cohen d=0.86) and a significant and moderate effect on the mental component scale of the SF-12 (P<.001, Cohen d=0.66) and the EQ-VAS (P<.001, Cohen d=0.62). Overall, 60% (n=43) of the iCBT group completed all 7 modules, whereas 82% (n=59) completed at least half of the modules. No patients were discontinued from the study owing to a high risk of suicide or deterioration in depression. CONCLUSIONS: Nurse-delivered iCBT can reduce depression and improve HRQoL in patients with CVD, enabling treatment for depression in their own homes and at their preferred time. TRIAL REGISTRATION: ClinicalTrials.gov NCT02778074; https://clinicaltrials.gov/ct2/show/NCT02778074.

Dapagliflozin lowers blood pressure in hypertensive and non-hypertensive patients with type 2 diabetes.

The effect of dapagliflozin on blood pressure was evaluated in non-hypertensive (<140 mm Hg) and hypertensive (⩾140 mm Hg) patients with type 2 diabetes mellitus. Data were pooled from 13 placebo-controlled studies. Patients received dapagliflozin 10 mg/day (n = 2360) or placebo (n = 2295) for up to 24 weeks. Dapagliflozin was associated with placebo-subtracted changes from baseline in systolic and diastolic blood pressures of -3.6 and -1.2 mm Hg, respectively, in hypertensive patients and -2.6 and -1.2 mm Hg, respectively, in non-hypertensive patients. At 24 weeks, a similar proportion of patients experienced measured orthostatic reactions with dapagliflozin versus placebo in hypertensive (6.1% and 6.6%, respectively) and non-hypertensive (4.0% and 4.2%) patients. No clinically relevant difference was observed between dapagliflozin and placebo in heart rate. In conclusion, dapagliflozin 10 mg induces a modest reduction in blood pressure compared with placebo in patients with diabetes with a low risk of orthostatic reactions, regardless of baseline blood pressure.