Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularisation in patients with stable angina pectoris: study protocol for the PRO-FIT randomised controlled trial

A consortium with experts from multiple domains was established to discuss and design this intervention. Specifically, we included the following experts; multiple cardiologists and physical therapists, a dietician, sports physician, medical psychologist, nutritional expert, medical physiologist, and an IT specialist. The study team was divided into several working groups, consisting of 7–11 individuals, to advise on the domain-specific content of the multidisciplinary CR intervention (physical exercise, nutrition, psychology and behavioural change, information technology and logistics). After 2–3 meetings, the evidence based aspects of the domain-specific intervention were integrated in a comprehensive CR programme. Details of this CR programme are described in the following paragraphs. Healthcare professionals responsible for delivering the CR programme were trained by the researchers and/or experts from the study team.

A personalised, secured, patient-centred online platform with separate dashboards for patients and care professionals will be used for monitoring and coaching (FLOW platform, Mibida B.V., Eindhoven, The Netherlands). Patients are provided a smartwatch (Galaxy Watch Active2, Samsung, South Korea) at the start of the study to monitor heart rate during training sessions, including the time spent in the set heart-rate zone, and daily physical activity energy expenditure. Data will automatically be uploaded to the online platform by a secured cloud based solution.

The platform enables patients to register and adjust rehabilitation goals, review exercise training and activity data, monitor food intake with an integrated chatbot and conduct video consulting. Details of the platform were described earlier in a study protocol by Brouwers et al. [19]. Furthermore, it includes an integrated platform that promotes healthy behaviour through unified health gamification (GameBus, Eindhoven, The Netherlands) by involving the patients’ social environment and facilitating interaction with peers [20].

During phase 1 (month 1–3) all patients will follow an exercise training programme at a primary care physiotherapy practice. This exercise programme is designed to improve fitness, particularly by stimulating direct, exercise-induced effects on myocardial flow, endothelial function and arteriogenesis [21]. This will expectedly lead to improved coronary perfusion as demonstrated by previous studies in SAP patients [9, 22]. All physiotherapists are trained in cardiac rehabilitation and are part of Chronisch ZorgNet (a Dutch, national network of specialised therapists who offer supervised exercise therapy and lifestyle guidance). Patients will receive aerobic and resistance training, integrated in 20 face-to-face sessions. The aerobic training, consisting of continuous training, starts with a build-up phase in the first 2 weeks (40–50% heart rate reserve (HRR)), in which the patients get familiar with training. From week 3 forward the aerobic training intensity will be gradually increased to a target of 65–75%HRR. The resistance training will also start with a build-up phase in the first 2 weeks (30–40% 1 repetition maximum (1RM)) after which the training intensity will be gradually increased to a target of 50–80% 1RM. The training prescription is provided in Table 2. During phase 1, patients will receive education on how to incorporate exercise training and physical activity in their home environment. In achieving this goal, training data from their smartwatch will be used and visualised in the online platform for feedback purposes. From week 3 onwards, patients are stimulated to perform exercise training at home. The home-based exercise at this stage involves low-intensity exercise, with the moderate-to-high intensity exercise being restricted to the training sessions with the physiotherapist. From week 9 onwards, patients are instructed to also perform moderate-to-high intensity exercise training sessions at home using the target training intensity that is being adopted during the session with the physiotherapist. Frequency of this type of home-based training is once a week and intensity will be recorded using the smartwatch and online feedback. After 3 months, at the end of phase 1, the training goals of the patient will be evaluated and new or residual goals will be formed in consultation with the patient using the outcome measurements of this evaluation.

The second phase (month 3–6) is aimed at the transfer of exercise training to the home environment. To this end, patients are advised to perform exercise training sessions in their home environment to reach their new or maintain previously set training goals with remote supervision. Patients are instructed to adhere to the Dutch physical activity guidelines 2017 [23] and perform two training sessions a week on a pre-set heart rate zone, which has been set in phase 1. In short, phase 2 exercise training will consists of:

A video consultation of 10–20 min with a mentor from the core study team is scheduled every two weeks (or weekly, depending on patient preference) during this phase. During these video consultations, both the exercise data and, if appropriate, questionnaire results are evaluated and targets are adjusted if needed. These consultations are based on semi-structured interviews, in which the principles of motivational interviewing are applied [24‐26]. Patients will be prepared for phase 3 and learn to adjust their own training and activity goals.

In phase 3 (month 6–12), we aim for sustained long-term effects to prevent progression of atherosclerosis. To achieve this, the intervention will contain a relapse prevention programme for six months after ending the second phase. Patients will be stimulated to continue performing exercise in their home environment, with the exercise goals set at the end of phase 2. In phase 3, coaching is only performed on an on-demand basis. The web application enables weekly evaluation of the exercise training and physical activity data and generates alerts in case of non-compliance (not uploading sensor data for 1 week), exceeded set heart-rate zones (> 20 min a week) and reduced physical activity. Reduced physical activity is defined as a decrease of 50% in total steps (average per week), a decrease of 50% in time spent in the moderate to vigorous activity zone (average per week), an exercise time that is 75% less than the Dutch Health Council guidelines or not attending or uploading two exercise sessions in a week. Coaching sessions can be initiated by caregivers to address the alerts or by patients if there are any questions.

Every patient will receive 3 consultations with a dietician within the first 3 months. Based on a dietary assessment at baseline, patients will get a personalised dietary advice following the Dutch Health Council guidelines for healthy nutrition and specifically focusing on cardiovascular health and reducing residual risk [27]. This assessment is done using the LifeStyleScore, which contains questions on 16 dietary domains derived from the Dutch Health Council guidelines. The dietary assessment will be repeated every 3 months to set new or adjust existing nutritional goals. To stimulate adherence to a healthy diet, a chatbot will be used. This chatbot will monitor the progress on personal goals and increases patients´ awareness by asking about their intake and showing the results in the online platform. A full day recall will be assessed at least every five days, up to daily, depending on a patient's personal preference.

Every patient will receive access to an information module. This module consists of 10 short videos, recorded by professionals, containing information about several relevant topics such as clinical trial information, coronary artery disease, medication and a healthy lifestyle (e.g. exercise, nutrition, smoking cessation, stress, work, maintaining a healthy lifestyle).

The lifestyle PEP module is a structured behavioural change programme that uses psychoeducation and evidence-based techniques in guiding patients towards their goals. These techniques include; cognitive behavioural therapy, motivational interviewing, solution focused therapy, acceptance and commitment therapy, positive psychology and mindfulness. The programme focuses on the patients’ preferences and on aspects in their lifestyle that can be altered to reduce the risk of recurrence and/or worsening of cardiovascular disease. In general, these themes are exercise, smoking, weight loss, alcohol, nutrition, and stress (BRAVO themes). This is in accordance with the Dutch CR guideline [28]. The PEP module consists of three individual telephone coaching sessions with a lifestyle coach (month 5, 7 and 9) and, if indicated, also of PEP group sessions in month 1–4.

At baseline, a psychological screening is performed through a combination of questionnaires assessing symptoms of depression, anxiety and stress according to the Dutch Society for Cardiology CR-guideline [18]. If indicated, patients are referred to relaxation therapy or to a registered psychologist for individual treatment.

If patients smoke they are referred to a smoking cessation programme based on group training, telephonic coaching or personal coaching, based on the patient’s preference.

The primary outcome measure is the change in angina symptoms from baseline to 12 months, which will be compared between the intervention and control group to answer the main research question. The quantity of angina symptoms will be evaluated by the shortened Seattle Angina Questionnaire (SAQ-7) [29]. The SAQ-7 has good validity and reproducibility in patients with angina pectoris and correlates with prognosis [29]. Furthermore, through its limited length it can easily be used in routine clinical practice.

Secondary clinical outcome measures include ischemic threshold, major adverse cardiac events, health-related quality of life, physical fitness, cardiovascular health, psychosocial wellbeing and physical activity pattern. See Table 3  for the assessment schedule.

For the second aim of this study, a cost analysis, cost-utility analysis and budget impact analysis will be performed at baseline, 3, 6, 9 and 12 months, comparing the intervention- and control group.

For the cost analysis, the primary analysis will be based on the comparison between the two treatment arms. Cost is usually a parameter with a skewed distribution. If this occurs, as well as possible heteroscedasticity, cost analysis will be performed using a generalised linear model with a log ink function relating the conditional mean to independent variables and using a gamma distribution specifying the relationship between the variance and the mean.

For the utility analysis, health utility scores over time will be used. Quality adjusted life years will be calculated by taking the product sum of the health utility scores and the periods in-between successive measurements during the 12 months of follow-up according to the trapezium method. Utilities will be analysed using tobit regression.

The cost-utility analysis integrates costs and utilities to an Incremental Cost-Effectiveness Ratio with bootstrapped confidence intervals surrounding the point estimate of this ratio.

Analysis will be carried out in the statistical software package R.