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Preventive treatment goals for blood pressure and cholesterol levels continue to be unmet for many coronary patients. The effect of drug treatment depends on both its appropriateness and the patients’ adherence to the treatment regimen. There is a need for adherence interventions that have a measurable effect on clinical outcomes.
This study aims to evaluate the effects on treatment goals of an intervention designed to improve patient adherence and treatment quality in secondary prevention of coronary heart disease. A protocol for the prespecified process evaluation of the trial is published separately.
The Motivational Interviewing and Medication Review in Coronary heart disease (MIMeRiC) trial is a prospective, randomized, outcomes-blinded trial designed to compare individualized follow-up by a clinical pharmacist using motivational interviewing (MI) and medication review with standard follow-up. Patients were randomized to 2 groups after stratification according to their beliefs about medicines. After standard follow-up at the cardiology clinic, patients in the intervention group are seen individually by a clinical pharmacist 2 to 5 times as required over 7 months, at the clinic. The pharmacist reviews each patient’s medication and uses MI to manage any problems with prescribing and adherence. The primary study outcome is the proportion of patients who have reached the treatment goal for low-density lipoprotein cholesterol by 12 months after discharge. Secondary outcomes are the effects on patient adherence, systolic blood pressure, disease-specific quality of life, and health care use.
The protocol for this study was approved by the Regional Ethics Committee, Linköping, in 2013. Enrollment started in October 2013 and ended in December 2016 when 417 patients had been included. Follow-up data collection will conclude in March 2018. Publication of the primary and secondary outcome results from the MIMeRiC trial is anticipated in 2019.
The MIMeRiC trial will assess the effectiveness of an intervention involving medication reviews and individualized support. The results will inform the continued development of support for this large group of patients who use preventive medicines for lifelong treatment. The design of this adherence intervention is based on a theoretical framework and is the first trial of an intervention that uses beliefs about medicines to individualize the intervention protocol.
ClinicalTrials.gov NCT02102503; https://clinicaltrials.gov/ct2/show/NCT02102503 (Archived by WebCite at http://www.webcitation.org/6x7iUDohy)
Coronary heart disease (CHD) is the leading cause of death worldwide, and an aging population means that the number of people affected by the disease is increasing [
The reasons for nonadherence are multiple and individual, and therefore, any attempted intervention must have a broad approach to inventorying problems and must allow for individualized problem solving to be effective in a wide group of patients [
A recent review of interventions for patients with CHD suggests that simple adherence interventions might be as effective as complex ones, but this review only studied effects on adherence, and in half of the included studies, patients were followed up only for 6 months or less [
The theoretical framework for the intervention evaluated in this study is described in detail in a separate manuscript, which also describes the development from pilot study and the study protocol for evaluation of the intervention process [
The primary objective of this trial was to evaluate the effects of MI and a medication review, as part of a secondary prevention program in patients with CHD, on achieving goal levels of low-density lipoprotein cholesterol (LDL-C) by 12 months after discharge, compared with standard care.
The secondary objectives were to evaluate the effects of the intervention on systolic blood pressure, adherence to secondary prevention drugs, health-related quality of life (general and disease-related), and secondary care use. A health economic assessment will also be conducted, but this is not described in detail in this study protocol.
Motivational Interviewing and Medication Review in Coronary heart disease (MIMeRiC) is a randomized, controlled, outcomes-blinded, superiority trial with two parallel groups. Patients have been randomized to standard care (control) or standard care plus a follow-up program that includes medication review and MI (intervention). Ethical approval has been obtained from the Regional Ethics Committee, Linköping, Sweden (Dnr-2013/236-31). The trial is registered in clinicaltrials.gov (NCT02102503).
Patients with CHD (International Classification of Diseases-10 I20-I21) were recruited from the cardiology unit at the County Hospital in Kalmar, Sweden. This is a 400-bed teaching hospital in rural Sweden; the cardiology unit has 30 beds and performs around 1300 angiographies and 600 percutaneous coronary interventions a year, but no open-heart surgery. All patients with coronary artery disease, regardless of how acute it was, were chosen because they all undergo the same standard follow-up at the outpatient clinic. See
Inclusion criteria:
Patients must:
speak Swedish
have an angiography during their hospital stay
be scheduled for follow-up at the out-patient clinic in Kalmar
have verified coronary artery disease (International Classification of Diseases-10 I20-I21)
Exclusion criteria:
Patients are excluded if any of the following conditions apply:
cognitive impairment or any other condition making interviews or phone calls difficult
nonparticipation in the standard follow-up at the outpatient clinic
prior participation in this study
The recruitment of patients was changed during the study because of practical problems with screening. This change was judged not to affect the generalizability of the result, and it was verified by the Regional Ethics Committee.
Patients admitted to the coronary angiography unit were screened for eligibility, and eligible patients were given written and verbal information about the trial by a nurse or a study pharmacist and were invited to take part. Patients who agreed to participate were contacted within 2 weeks by a pharmacist who explained the implications of the research and asked for informed consent (documented by the pharmacist during the phone call).
Patients scheduled for a follow-up visit to a cardiology nurse 2 weeks after discharge were screened for eligibility. Eligible patients were given written information to read in the waiting room, and verbal information was given by the nurse. The nurse explained the implications of the research and asked for written informed consent.
The patients were randomized in blocks of 10, stratified according to their attitudes toward their heart medicines, as measured by the Beliefs about Medicines Questionnaire-Specific (BMQ-S) [
The intervention is a follow-up program run by a clinical pharmacist, which is carried out in addition to the standard care. The clinical pharmacist carries out MI and reviews the patient’s medication. The mainstay of the intervention consists of two appointments at the cardiac outpatient clinic, but this is adjusted according to the patient’s needs. For a full list of study events, see
Intervention participants are scheduled for a 60-min appointment with the clinical pharmacist, following their standard follow-up appointments at the clinic, around 3 months after discharge. The pharmacist prepares an advanced medication review [
Study flow chart. Each box represents a separate event. White boxes are standard care events, light gray boxes are study events; BMQ-S: Beliefs about Medicines Questionnaire-Specific; BP: blood pressure; LDL-C: low density lipoprotein cholesterol; QoL: quality of life.
The clinical pharmacist uses MI when seeing the patient. An agenda is set to focus the interview on how the medication works for the patient, what it means in terms of side effects, the patient’s worries, their understanding of the purpose of the medicines, and their thoughts about risks and benefits. The goal is that the patient should feel safe and secure with their medication, and that any problems affecting adherence or quality of life will be found and solved together. If the medication review indicates a need for intensifying the treatment, this is first discussed with the patient to assess their readiness for change. At the end of the consultation, the pharmacist prepares a written summary of the discussed issues and the agreed next steps. The summary is given to the patient together with the next scheduled appointment time.
Any drug-related problems that cannot be solved by the pharmacist and patient together are discussed with the cardiologist after the visit either in person or via the EHR, and the pharmacist then contacts the patient by phone if prescription changes are made. The pharmacist documents the assessment and findings in the EHR.
Schedule of events by treatment arm.
Study event (including standard care) | Control | Intervention | |
Discharge | Always | Always | |
Nurse visit (2 weeks after discharge) | Always | Always | |
Physical training in cardiac rehabilitation is offered | Always | Always | |
Referral to welfare officer | If needed | If needed | |
Physician visit (around 2 months after discharge) | Always | Always | |
Extended follow-up in cardiac clinic or primary-care facility | If needed | If needed | |
Referral to primary-care facility | Always | Always | |
Medication review and MIa | Always | ||
Written summary of discussion | Always | ||
Discussion with cardiologist if problems with cardiac drugs or treatment goals | If needed | ||
Referral to primary-care facility if problems with other drugs | If needed | ||
Follow-up phone call | Always | ||
Up to four extra contacts by phone or in person | If there are negative attitudes or drug-related problemsb | ||
Medication review and MI | Always | ||
Written summary of discussion | If needed | ||
Follow-up phone call | If needed | ||
Referral to primary-care facility if problem with any drug or treatment goal | If needed |
aMI: motivational interviewing.
bIntensified intervention is not a randomized treatment arm.
The pharmacist makes a follow-up phone call 2 weeks after the visit to enquire about the agreed changes, to see if there are new questions, and to strengthen the message from the interview.
The pharmacist reviews the EHR for any changes in health and prescribing, and monitors the lipid profile (the patient receives a referral for a laboratory test along with the scheduled appointment), before seeing the patient. The patient’s beliefs about medicines are reassessed, and MI is used to elicit the patient’s thoughts and problems. The consultation, which lasts approximately 20-30 min, aims to support the patient for their coming lifelong (supposedly) medicine use and to guide them to obtain follow-up at a primary care facility if they have no established primary care contact. Any problems found at this stage are communicated to the primary care physician, either through referral or with a personal message in the EHR. A written summary is provided and a follow-up phone call is made only if new problems are encountered.
The intervention protocol is adjusted according to the patient’s beliefs about medicines or need for support. If the patient is assessed as accepting at baseline, the pharmacist can shorten the initial consultation to 30-40 min if appropriate. If the patient has negative beliefs, that is, ambivalent, skeptical or neutral, the pharmacist arranges a more thorough interview and offers the patient more visits or continued contact by phone. This more intensive intervention protocol offers the patient up to four extra contacts, either in person or by phone, as an extension of the first visit. During the first visit, the pharmacist and the patient decide together whether the patient’s worries or drug-related problems require more contacts.
The intervention is performed by two clinical pharmacists (LH and MJÖ) with training in both medication review and MI. One of the pharmacists has formal specialist training in clinical pharmacy, focusing on cardiovascular medicine (60-credit Master’s program in clinical pharmacy at Uppsala University, Sweden) and has completed a 15-credit course in MI from Linnaeus University, Sweden. The other has completed a 12-credit course in clinical pharmacy and pharmacotherapy from Lund University, Sweden, 2 days of internal training in MI, and a 3-day course run by a member of Motivational Interviewing Network of Trainers. Both pharmacists have carried out 5 consultations coded by Motivational Interviewing Treatment Integrity 3.1 with feedback and, in at least one of these, have been evaluated as “beginning proficiency” (≥3.5) in the global rating of MI-spirit.
Participants in the control group receive standard care only. Standard care at the cardiology unit of the County Hospital in Kalmar comprises a 60-min appointment with a cardiac specialist nurse 2 weeks after discharge and a 60-min appointment with an assistant physician or cardiologist about 2 months after discharge. Unless the patient requires specialist follow-up or more treatment at the cardiac clinic, referral is made to the primary care facility for continuing follow-up. All patients are also offered cardiac rehabilitation such as physical training in a group at the hospital or at a primary care facility closer to home. See
Baseline assessment data, including demographics, level of education, civil status, CHD presentation type, previous CHD history, comorbidities, smoking status, type of cardiovascular intervention, and prescribed medicines, were collected from the EHR by a member of the research staff before randomization. Further baseline data were obtained from questionnaires sent to the participants by mail after their physician visit at the cardiology clinic with instructions to return them within 10 days; these questionnaires covered medication adherence, beliefs about medicines, and health-related quality of life. Baseline data on lipid status and blood pressure were collected from the EHR. See
To promote participant retention, control group patients receive a postal card stating the appreciation of the research team for their return of questionnaires at baseline and 10 months. Intervention group patients do not receive a card as they are instead summoned for a visit.
Lipid status and blood pressure are assessed 12-14 months after discharge. Patients who have had a myocardial infarction are followed-up at 12-14 months by the national quality register SEPHIA (Secondary prevention after Heart Intensive care Admission), and assessments of lipids and blood pressure are therefore recorded in the EHR. We use these data so that participants do not need an extra assessment because of the study. For noninfarction patients, the research team arranges for the assessment of lipids and blood pressure. All patients contacted by either SEPHIA or the research team receive a referral for a laboratory test and blood pressure measurement, which they can choose to do at the drop-in clinic at the hospital or at their primary care facility.
At 15 months postdischarge, participants complete all questionnaires for the outcomes assessment: Morisky 8-item adherence scale (MMAS-8), BMQ-S, EuroQoL 5 Dimensions 5 Levels, and HeartQoL questionnaire. A time of 15 months was chosen to relate the answers on the MMAS-8 to the pharmacy refill date 12-16 months after discharge. Data are collected from the Swedish Drug Prescription Register (adherence), the Health Care Register of Kalmar County (hospital admissions), and, for deceased participants, the registry of Causes of Death administered by the National Board of Health and Welfare.
Because randomization took place after the standard care process, the doctors and nurses involved in these standard visits did not know whether their patients would be in the control or the intervention group. This introduced a control for bias during the standard care period. However, this control is lost for doctors with whom the pharmacist discusses treatment during subsequent periods of the study, as it will be obvious that they are discussing intervention patients, and for doctors and nurses involved in the care of those intervention patients who have further contact with the clinic after the standard follow-up. Pharmacists are not involved in any care of patients at the cardiology clinic outside of this study.
All the outcomes data (returned questionnaires, prescription fill data, and health care use) for each patient are collected in an individual, coded, clinical research form (CRF). Data from registers and the EHR are collected by a blinded research assistant who is not involved with the care of the study patients. Researchers will enter the data from the coded CRFs into the database.
To assess selection bias, all participants will be compared with eligible patients who declined to participate, in terms of age, sex, type of CHD, new or recurrent CHD, and marital status.
The primary analysis will take place 16 months after inclusion of the last patient, according to the intention-to-treat principle. The primary outcome will be analyzed using logistic regression models. Secondary outcomes will be analyzed with appropriate statistical methods based on the type of data. Primary and secondary regression analyses will be adjusted for baseline variables. Per protocol analyses will also be performed. All tests will be two-sided and a
In quality registry data from 2012, the proportion of patients achieving the LDL-C treatment goal in Kalmar was less than 0.3 [
Study assessment schedule indicating when data is collected.
Collection of data | Discharge | Nurse visit at 2 weeks | Physician visit at 2 months | Baseline questionnairea | 10 months | 12 months | 15 months | |
Patient eligibility | ✓ | |||||||
Patient informed consent | ✓ | |||||||
Patient medical history | ✓ | |||||||
Demographics | ✓ | |||||||
Medications | ✓ | ✓ | ||||||
Lipid panel | ✓ | ✓ | ✓ | |||||
Systolic blood pressure (EHR) | ✓ | ✓ | ||||||
BMQ-Sc | ✓ | ✓ | ✓ | |||||
Heart-QoL | ✓ | ✓ | ||||||
EQ-5D-5Le | ✓ | ✓ | ||||||
Self-reported | ✓ | ✓ | ||||||
Pharmacy refill | ✓ | |||||||
Hospital admissions | ✓ |
aSent after the physician visit.
bEHR: electronic health record.
cBMQ-S: Beliefs about Medicines Questionnaire-Specific.
dQoL: quality of life.
eEQ-5D-5L: EuroQoL questionnaire [
Another registry, the national “Öppna Jämförelser” (Open Comparisons), measures the proportion of patients who have had a myocardial infarction and who fill a prescription for a statin 12-16 months later. The report from 2012 stated that 80% of myocardial infarction patients from Kalmar County Hospital filled a statin prescription [
We assumed an attrition rate of 40% in the intervention group and 60% in the control group, because the protocol for the latter can be regarded as an extended questionnaire study. Because patients were enrolled about 2 months before they were asked to fill in the first set of questionnaires, we assumed a high attrition rate at this stage, and because they are volunteers, we wanted withdrawal from the study at this stage to be a simple process. Patients who did not answer these first questionnaires will not be included in the outcome analyses.
On the basis of our primary outcome (LDL-C goal achievement) and expected attrition rate, a sample size of 130+140 patients (intervention plus control) would be required. However, this would not have the power to detect a meaningful difference in adherence (one of the secondary outcomes). As one of the problems encountered in prior intervention studies has been the lack of power to detect differences in both adherence and clinical outcomes, we based our sample size calculation on the number required to show a difference in adherence, that is, 195 patients at follow-up.
We therefore aimed to include 273+312 (=585) patients in the intervention and control groups, with an allocation ratio of 1:1.14.
During the study, we learned two things that greatly impacted our sample size: (1) the goal achievement in standard care improved significantly and (2) our assumed attrition rate was too high. As described earlier, problems with recruitment also delayed the study, and this was another incentive to look at the required sample size.
The goal achievement for LDL-C in 2012 did not reflect the circumstances during our follow up in 2014-2017 because treatment possibilities changed the likelihood of reaching the target (the atorvastatin patent expired in 2013 and local guidelines successively changed, based on this). In 2015, the proportion of patients reaching the target was 0.5 nationally and 0.45 at Kalmar Hospital [
The primary outcome parameter of the MIMeRiC trial is the proportion of patients who reach the treatment goal for LDL-C levels. The treatment goal, as assessed by SEPHIA, is an LDL-C of <1.8 mmol/L, or a reduction of 50% from baseline.
LDL-C was chosen as the primary outcome because it is an objective measure of a variable related to the risk of recurrent disease. The national quality registry data indicate that it is more difficult to reach treatment goals for LDL-C than for systolic blood pressure [
The assessment of LDL-C is part of the follow-up process in SEPHIA, and the test is administered by the cardiology outpatient clinic for all patients with acute myocardial infarction. Patients with other forms of CHD will be followed by the research team for this assessment and asked to go to their primary care facility or the cardiology outpatient clinic for assessment, whichever is most convenient for them. LDL-C values are calculated from the serum concentrations of cholesterol and fasting triglycerides, using the Friedewald formula.
The proportion of patients who adhere to the treatment regimen will be assessed using self-reporting and refill data. The phases of adherence under study are implementation and persistence, as defined by the ABC-taxonomy [
Self-reported adherence to cholesterol-lowering drug regimens will be measured with the MMAS-8 [
Refill adherence will be assessed using the Swedish Prescribed Drug Register. Patients will be defined as nonpersistent if they have not purchased the drug at least once during the 12- to 16-month period after discharge. The 4-month period is based on the Swedish reimbursement system [
We will also measure the proportion of patients with systolic blood pressure <140 mm Hg 12 months after discharge. As for LDL-C, this is part of the second follow-up in SEPHIA. Patients not included in the SEPHIA registry will be followed by the research team and asked to attend their primary care facility or the cardiology outpatient clinic for assessment, whichever is most convenient for them.
Changes in quality of life will be measured with the HeartQoL [
Information about the patients’ unscheduled secondary care use will be collected from the health care register in the County of Kalmar. The number of emergency visits or hospitalizations due to cardiovascular disease and the time to first contact will be recorded for each group. Data will also be collected retrospectively for the 10-year period before the index date so that adjustments can be made as required.
A total of 417 patients were included in the study before recruitment stopped in December 2016, see
Baseline characteristics have been registered in our database for the 234 subjects with baseline data collected before September 2016; these are described in
Flow diagram of study participants, status as of April 2017. For those excluded, (i) indicates cognitive impairment or any other condition making interviews or phone calls difficult; (ii) indicates nonparticipation in the standard follow-up at the out-patient clinic; and (iii) indicates prior participation in this study. LDL-C: low-density lipoprotein cholesterol; BP: blood pressure.
Baseline characteristics of the first 234 subjects enrolled into the Motivational Interviewing and Medication Review in Coronary heart disease (MIMeRiC) study for whom complete baseline data are available.
Variable | All subjects | |
Age (y), mean (SD) | 68 (10.3) | |
Male, n (%) | 173 (73.9) | |
STEMIa, n (%) | 68 (29.1) | |
non-STEMI, n (%) | 63 (26.9) | |
Unstable angina, n (%) | 30 (12.8) | |
Chronic angina, n (%) | 50 (21.4) | |
Other reason for PCIb, n (%) | 15 (6.4) | |
History of CHDc, n (%) | 66 (28.2) | |
Necessity score, mean (SD) | 18.5 (3.8) | |
Concern score, mean (SD) | 12.9 (5.1) | |
Accepting, n (%) | 113 (48.3) | |
Ambivalent, n (%) | 75 (32.1) | |
Neutral, n (%) | 24 (10.3) | |
Skeptical, n (%) | 21 (8.9) |
aSTEMI: ST-elevation myocardial infarction.
bPCI: percutaneous coronary intervention.
cCHD: coronary heart disease.
Medicines prescribed at discharge to the first 234 patients enrolled in the Motivational Interviewing and Medication Review in Coronary heart disease (MIMeRiC) study.
Medicine prescribed | At discharge, n (%) | New prescriptiona, n (%) |
ASAb | 202 (85.6) | 126 (53.4) |
Clopidogrel | 81 (34.3) | 69 (29.2) |
Ticagrelor | 119 (50.4) | 118 (50.0) |
Warfarin | 20 (8.5) | 8 (3.4) |
ACEic | 119 (50.4) | 80 (33.9) |
ARBd | 86 (36.4) | 36 (12.7) |
BBe | 206 (87.3) | 132 (55.9) |
Statin | 217 (91.9) | 139 (58.9) |
aPatients who have received a medicine for the first time.
bASA: acetylsalicylic acid.
cACEi: angiotensin converting enzyme inhibitor.
dARB: angiotensin receptor II blocker.
eBB: beta-blocker.
This protocol describes the methodology for a study assessing the effectiveness of an intervention involving extended follow-up of the pharmacological treatment of patients with CHD using MI and medication review. Our randomized controlled trial acknowledges that optimal prescribing and monitoring of medications as well as high patient adherence is a prerequisite for adequate secondary prevention.
The aim of the intervention is to improve secondary prevention of CHD, and the effectiveness will be measured by assessing patient adherence as well as intermediate biological outcomes such as relevant treatment outcomes, perceived quality of life, and number of hospital admissions. We use two complementary adherence measures: self-report and pharmacy refill for the cholesterol drugs, which are directly linked to the primary outcome: LDL-C.
The design of this adherence intervention is based on a theoretical framework and it is the first trial of an intervention that uses beliefs about medicines to individualize the intervention protocol. Many adherence interventions have failed to assess or find long-term effects. Because this intervention follows the patient throughout the year after hospitalization for CHD and targets all patients regardless of adherence, we hope that it can prevent patients from discontinuing their medicines in the long term. It has been shown that the greatest loss in adherence (persistence) is during the first year and that patients who are persistent at 2 years continue to be adherent [
Patients were recruited directly after their acute event or treatment for chronic CHD and were invited to participate regardless of age and comorbidities as long as they underwent the standard follow-up procedure at the clinic. However, because the intervention involves extra contacts with the hospital, some patients will decline participation; this could create a selection bias, especially among patients who live far from the hospital or patients with multi-morbidity or greater age. A limitation of this study is that it is conducted in one single hospital clinic. The findings may thus be generalizable to other clinics only in a limited manner.
The duration of follow-up is 12 months from the start of the intervention (ie, 15 months after discharge) for the outcomes measured by the study itself: adherence, quality of life, and hospital admissions. However, for practical reasons, we chose to use the follow-up at 12 months after discharge for measuring lipids and blood pressure, because these tests are already in place for the quality register for secondary prevention of myocardial infarctions. We acknowledge that 12 months’ follow-up might be too short to assess the effect on hospital admissions due to cardiovascular disease if the intervention primarily affects how patients manage their drugs in the longer perspective, and therefore, we aim to assess this outcome again after 3, 5, and 10 years.
The broad inclusion criteria and few exclusion criteria strengthen the generalizability of the study. The many outcomes of the study, from adherence and LDL-C to quality of life and hospital admissions, is another strength. Few adherence studies have used two adherence measures and are also designed to analyze a relevant clinical outcome, with follow-up of 1 year [
After initiation of the study, we faced obstacles with our recruitment process, mainly due to patients not being identified for eligibility testing before discharge. We tried to remedy this by increasing the input from the research team, but after several months, without much difference in recruitment, we decided to change the procedure. This required the omission of a medication reconciliation that was initially part of the protocol for both study groups, as it was done at the inclusion phone contact before randomization. The reconciliation was appreciated by the nurses involved in the follow-up, but changing this meant little in the actual care of patients because the nurses were able to carry out a reconciliation during their consultation. After including the specialist nurses in the recruitment process, the enrollment rate increased markedly.
As described in the Methods section, the patent for atorvastatin expired during the study period, which resulted in more patients being treated with this drug as first-line treatment. This meant that more patients reached their treatment target without need of treatment assessment or changes in prescribing. We therefore recalculated our needed sample size based on more relevant presumptions. Another change affecting treatment was the release of the new American guidelines on treatment of blood cholesterol late in 2013 [
During the study, we also learned that patients undergoing a coronary artery bypass graft operation were sometimes recruited into the study up to 6 months before their treatment actually took place. Because these are only a minority of the study participants, we will conduct a sensitivity analysis with this group excluded in the outcomes analysis.
Patients today have concerns about their drugs because of what they read in the papers [
Beliefs about Medicines Questionnaire-Specific
coronary heart disease
clinical research form
electronic health record
low-density lipoprotein cholesterol
Motivational Interviewing
Motivational Interviewing and Medication Review in Coronary heart disease
secondary prevention after heart intensive care admission
This work was supported by The Kamprad Family Foundation for Entrepreneurship, Research and Charity.
MJO contributed to the study design, data collection, and first draft of the manuscript. TE contributed to the study design and review of manuscript. GP contributed to the study design and review of manuscript. LH contributed to the study design, data collection, and review of manuscript. All authors have approved the final paper.
None declared.