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We investigated whether a nurse-led, telephone-based follow-up including medical titration was superior to usual care in improving blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) values 36 months after acute coronary syndrome (ACS). We screened all patients admitted with ACS at Östersund hospital, Sweden, between January 1, 2010, and December 31, 2014, for inclusion based on ability to participate in a telephone-based follow-up. Participants were randomly allocated to usual care or an intervention group that received counselling and medical titration to target BP < 140/< 90 mmHg and LDL-C < 2.5/< 1.8 mmol/L. The primary outcome was LDL-C at 36 months. Of 962 patients, 797 (83%) were available for analysis after 36 months. Compared to controls, the intervention group had a mean systolic BP (SBP) 4.1 mmHg lower (95% confidence interval [CI] 1.9–6.5), mean diastolic BP (DBP) 2.9 mmHg lower (95% CI 1.5–4.5), and mean LDL-C 0.28 mmol/L lower (95% CI 0.135–0.42). All P < 0.001. A significantly greater proportion of patients reached treatment targets with the intervention. After 36 months of follow-up, compared to usual care, the nurse-led, telephone-based intervention led to significantly lower SBP, DBP, and LDL-C and to a larger proportion of patients meeting target values.

Background: One of the leading causes of death and disability worldwide is cardiovascular disease (CVD), including acute myocardial infarction (AMI). Despite improvements in medical treatment, management, and care over the years and the halving of mortality in recent decades, there is considerable room for improvement. Following myocardial infarction (MI), a patient is at great risk for subsequent infarctions or other related complications. In addition, the risk of ischemic stroke is increased following MI. Secondary prevention after MI is paramount for reducing further complications and consists of lifestyle changes, optimised medical treatment, and risk factor control of blood pressure (BP) and blood lipid levels. Although secondary preventive measures are effective, the proportion of patients reaching set treatment target levels is disappointingly low.

Most patients are prescribed dual antiplatelet therapy (DAPT) following MI as part of their secondary preventive treatment. Several articles have been published on treatment efficacy based on comparisons with different kinds of antiplatelet drugs and in different combinations. However, little data specifically address the incidence of ischemic stroke after MI in real-world populations. In addition to antiplatelet treatment, secondary prevention comprises risk factor control of hypertension and hyperlipidaemia. Given the low proportion of patients reaching set target levels for BP and blood lipids, new strategies are needed.

Aims: The aim of this dissertation is partly to elucidate if the rapid change in preferred DAPT in Sweden, from clopidogrel to ticagrelor in addition to aspirin, affected the incidence of ischemic stroke in patients suffering AMI (paper I) and in patients suffering AMI who have a history of ischemic stroke (paper II).

The second part of the dissertation aims to investigate the feasibility and implementation of a randomised controlled trial of a nurse-led telephone-based secondary preventive program, and to assess the proportion of patients who can be included in an unselected acute coronary syndrome (ACS) population (paper III). Furthermore, the aim of the trial was to assess the long term results regarding systolic BP (SBP), diastolic BP (DBP), and low-density lipoprotein cholesterol (LDL-C) after 36 months of intervention and follow-up compared to a control group receiving usual care (paper IV).

Methods: Papers I and II examined the impact of a change in the antiplatelet regimen following MI in regard to ischemic stroke occurrence. Data were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (i.e., RIKS-HIA). The register was combined with the National Patient Register (NPR) and the Cause of Death Register (CDR) in order to obtain data on stroke occurrence. Patients with AMI and treated with either clopidogrel or ticagrelor were assigned to one of two cohorts, each covering a 2- year time period, with the initial prescription of ticagrelor (20 Dec 2011) used as a cutoff point. Patients in the early cohort (n=23,447) were treated exclusively with clopidogrel, whereas those in the later cohort (n=24,227) were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). In paper II, the same methodology was used, but with a study sample restricted to AMI patients with a history of ischemic stroke. In paper II, there were 1633 patients in the early cohort and 1642 in the late cohort. In the late cohort, 66.3% patients were treated with clopidogrel and 33.7% with ticagrelor. Kaplan–Meier analysis was used to assess the risk of ischemic stroke over time, with multivariable Cox regression analysis used to identify predictors of ischemic stroke. Nurse-based Age independent Intervention to Limit Evolution of Disease (Papers III and IV were based on the NAILED)-ACS trial. The NAILED-ACS trial was an open randomised controlled trial of whether a nurse-led telephone-based follow-up and medical titration after MI or unstable angina achieved lower levels of BP and LDL-C than usual care. In paper III, patients admitted for ACS during January 2010 and December 2013 were evaluated for participation. Factors predicting participation and non- participation were assessed using logistic regression. Mortality rates after one year among included and excluded patients and patients declining participation were assessed using Kaplan–Meier analysis. For paper IV, all patients admitted with ACS at Östersund Hospital between January 2010 and December 2014 were screened for inclusion based on their ability to participate in a telephone- based follow-up. Participants were randomised into two parallel groups, an intervention group and a control group receiving usual care. BP and LDL-C were measured at 1, 12, 24, and 36 months. The baseline consisted of randomised patients who completed the one-month follow-up. The intervention group  received counselling and medical titration to attain treatment targets (BP <140/<90 mmHg and LDL-C <2.5/<1.8 mmol/L). Adjusted means stratified by sex and type of ACS were calculated for SBP and DBP and LDL-C. The proportion of patients who achieved treatment target levels at the end of the study was also assessed.

Results: Among the general AMI population treated with either clopidogrel or ticagrelor, the incidence of ischemic stroke after one year was 2.8% in the early cohort vs. 2.4% in the late cohort (p=0.001) (paper I). The study population in paper II, in which all patients had a history of previous ischemic stroke, was overall older and had a higher prevalence of comorbidities than the population in paper I. In paper II, incidence of ischemic stroke in the early cohort was 12.1% vs. 8.6% in the late cohort (p<0.01). Corresponding incidence of intracranial bleeding for the population in paper II was a non-significant 1.2% vs 1.5%.

In the feasibility study of the NAILED-ACS trial (paper III), 907 patients were assessed for inclusion. Among these, 72.9% could be included (n=661), 146 patients (16.1%) were excluded, and 100 patients declined participation (11 %). Reasons for exclusion were mainly participation in another trial, dementia, inability to use a telephone, and advanced disease. Examples of predictors of both exclusion and declining participation were older age, lower functional status, and lower education. Non-participating patients had significantly higher mortality rates at one year compared to participating patients.

Paper IV presents the final results of the NAILED-ACS risk factor trial in which a total of 962 patients were randomised and completed the one-month follow- up. Of this group, 797 were available for analysis after 36 months. Compared to the control group, in the intervention group, mean SBP was 4.1 mmHg lower, mean DBP was 2.9 mmHg lower, and mean LDL-C was 0.28 mmol/L lower (p<0.001 for all). The proportions of patients reaching treatment target goals for SBP, DBP, and LDL-C were significantly higher in the intervention group. In regard to SBP, 77.6% of intervention patients achieved treatment target levels, compared to 62.9% in the control group. Corresponding numbers for DBP were 90.9% vs. 80.8% and for LDL-C, they were 65.6% vs. 53.1%

Conclusion: The incidence of ischemic stroke was significantly lower in a cohort of AMI patients following a change in preferred treatment from clopidogrel to ticagrelor (paper I). In AMI patients with a history of ischemic stroke (paper II), the incidence rate of ischemic stroke was significantly lower in the late cohort compared to the early cohort, and overall incidence rates were markedly higher than in paper I.

The NAILED-ACS trial was shown to be both feasible (paper III) and successful, with a higher proportion of patients reaching treatment target levels in the intervention group, and significantly lower mean values for SBP, DBP, and LDL- C (paper IV).

ObjectivesTo evaluate the impact of a rapid change in preferred treatment from clopidogrel to ticagrelor on the risk of ischemic stroke following acute myocardial infarction (AMI).MethodsData for AMI patients treated with either clopidogrel or ticagrelor were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). Patients were divided into two cohorts, each covering a two-year time period; the initial prescription of ticagrelor (20 Dec 2011) was used as a cut-off point. Patients in the early cohort (n=23,447) were treated with clopidogrel, while those in the later cohort (n=24,227), were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). Kaplan-Meier analyses were used to assess the risk of ischemic stroke over time, with multivariable Cox regression analyses used to identify predictors of ischemic stroke.ResultsOf 47,674 patients, there were 1203 cases of ischemic stroke. Cumulative Kaplan-Meier incidence estimates of ischemic stroke after one year were 2.8% vs. 2.4% for the early and late cohorts, respectively (p=0.001). Older age, hypertension, diabetes, previous stroke, congestive heart failure, atrial fibrillation, and ST-elevation myocardial infarction were associated with an increased risk of ischemic stroke. Percutaneous coronary intervention and statins at discharge were associated with a decreased risk of ischemic stroke, as was higher estimated glomerular filtration rate. Membership of the late cohort correlated with a 13% reduction in the relative risk of ischemic stroke.ConclusionsThe introduction of ticagrelor as well as an improved management of AMI was associated with a lower rate of ischemic stroke in a relatively unselected AMI population.

Studies of secondary prevention for cardiovascular disease show low fulfilment of guideline-recommended targets. This study explored whether nurse-led follow-up could increase adherence to statins over time and reasons for discontinuation. All patients admitted for acute coronary syndrome at Östersund hospital between 2010–2014 were screened for the randomized controlled NAILED-ACS trial. The trial comprises two groups, one with nurse-led annual follow-up and medical titration by telephone to reach set intervention targets and one with usual care. All discontinuations of statins were recorded prospectively for at least 36 months and categorized as avoidable or unavoidable. Kaplan-Meier estimates were conducted for first and permanent discontinuations. Predictors for discontinuation were analysed using multivariate Cox regression, statin type and mean LDL-C at end of follow-up. Female gender was a predictor for discontinuation. Allocation in the intervention group predicted increased risk for a first but decreased risk for permanent discontinuation. A nurse-led telemedical secondary prevention programme in a relatively unselected ACS cohort leads to increased adherence to statins over time, greater percentage on potent treatment and lower LDL-C compared to usual care. An initially increased tendency toward early discontinuation in the intervention group stresses the importance of a longer duration of structured follow-up.

Background: Previous ischemic stroke is a predictor of recurrent ischemic stroke after an acute myocardial infarction (AMI). Dual antiplatelet therapy, including a P2Y12-inhibitor, is important in secondary prevention after AMI. Ticagrelor, a P2Y12-inhibitor, is more potent than the commonly used clopidogrel. Here, we evaluated the impact of ticagrelor on the risk of ischemic stroke following AMI in patients with previous ischemic stroke.

Methods: Data for patients with AMI that had a previous ischemic stroke were obtained from the Swedish Registry of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients were assigned to early and late cohorts, each covering a two-year time period before and after, respectively, the introduction of ticagrelor prescriptions (20 Dec 2011). Patients in the early cohort (n = 1633) were treated with clopidogrel (100%); those in the late cohort (n = 1642) were treated with either clopidogrel (66.3%) or ticagrelor (33.7%). We assessed the risk of ischemic stroke and intracranial bleeding over time with Kaplan-Meier analyses. We identified predictors of ischemic stroke with multivariable Cox regression analyses.

Results: Of 3275 patients, 311 experienced ischemic stroke after AMI. Cumulative Kaplan-Meier incidence estimates of ischemic stroke within one year after AMI were 12.1% versus 8.6% for the early and late cohorts, respectively (p<0.01). Intracranial bleeding incidences (1.2% versus 1.5%) were similar between the two cohorts.

Conclusions: Ticagrelor introduction was associated with a lower rate of ischemic stroke, with no increase in intracranial bleeding, in an AMI population with a history of ischemic stroke.

Aims: It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population.

Methods and results: Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009-31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period (p=0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68-0.92; p=0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction.

Conclusion: The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.

Background: Secondary prevention after acute coronary syndrome (ACS) is crucial to prevent recurrent events. Multiple studies however show that patients often end treatments and for reasons unknown. Our aims in this study were to perform a prospective follow-up of persistence to statin treatment in a population based patient cohort after ACS, to explore the reasons for discontinuation, and to determine whether a nurse-based follow-up could improve persistence.

Methods: We studied patients recruited between 2010–2014 in the ongoing randomised controlled NAILED-ACS trial. All patients admitted with ACS at our County Hospital were eligible and exclusion criteria limited to inability to adhere to the study concept or participation in another trial. We randomised participants either to an intervention group with nurse-based telephone follow-up or to a control group with follow-up by a general practitioner (usual care). All participants were interviewed and screened yearly for blood pressure and blood lipids. The intervention group also got yearly counselling on healthy living and individualised titration of medicines to reach target values for blood pressure and blood lipids. We forwarded the measurements for the control group to the general practitioner for assessment. We collected information on adherence to statin treatment at the yearly interview and by review of medical records. Each reason for treatment discontinuation were recorded and classified as temporary or permanent.

Results: Out of 963 patients, 89.3% (n=434) in the intervention and 82.0% (n=391) in the control group were persistent to statin treatment after a median of 3.9 years of follow-up (p=0.001). The most prevalent reason for permanent discontinuation in the intervention group was advanced disease (27.5%, n=14) while in the control group it was side effects without a compelling relation to treatment (32.8%, n=22). A total of 27.8% (n=135) of the patients in the intervention group and 20.5% (n=98) in the control group discontinued treatment at some point during the period (p=0.009). The most common reasons for a first discontinuation were in both arms side effects without a compelling relation to treatment and lack of treatment motivation.

Conclusion: A nurse-based, long-term follow-up by telephone after an ACS with individualised medical adjustments results in a higher persistence to statin treatment than usual care.

Background. Secondary prevention after acute coronary syndrome (ACS) could reduce morbidity and mortality, but guideline targets are seldom reached. We hypothesized that nurse-led telephone- based intervention would increase adherence.

Methods. The NAILED ACS trial is a prospective, controlled, randomized trial. Patients admitted for ACS at Ostersund hospital, Sweden, were randomized to usual follow-up by a general practitioner or a nurse-led intervention. The intervention comprised telephone follow-up after 1 month and then yearly with lifestyle counselling and titration of medications until reaching target values for LDL-C (< 2.5 mmol/L) and blood pressure (BP; < 140/90 mmHg) or set targets were deemed unachievable. This is a 12-month exploratory analysis of the intervention.

Results. A total of 768 patients (396 intervention, 372 control) completed the 12-month follow-up. After titration at the 1-month follow-up, mean LDL-C was 0.38 mmol/L (95% CI 0.28 to 0.48, p< 0.05), mean systolic BP 7 mmHg (95% CI 4.5 to 9.2, p< 0.05), and mean diastolic BP 4 mmHg (95% CI 2.4 to 4.1, p< 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met by 94.1% and 91.9% of intervention patients and 68.4% and 65.6% of controls (p< 0.05). At 12 months, mean LDL was 0.3 mmol/L (95% CI 0.1 to 0.4, p < 0.05), systolic BP 1.5 mmHg (95% CI -1.0 to 4.1, p = 0.24), and mean diastolic BP 2.1 mmHg (95% CI 0.6 to 3.6, p < 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met in 77.7% and 68.9% of intervention patients and 63.2% and 63.7% of controls (p< 0.05 and p = 0.125).

Conclusion. Nurse-led telephone-based secondary prevention was significantly more efficient at improving LDL-C and diastolic BP levels than usual care. The effect of the intervention declined between 1 and 12 months. Further evaluation of the persistence to the intervention is needed.

Background: Acute coronary syndrome (ACS) is a major cause of death from a non-communicable disease. Secondary prevention is effective for reducing morbidity and mortality, but evidence-based targets are seldom reached and new interventional methods are needed. The present study is a feasibility study of a telephone-based secondary preventive programme in an unselected ACS cohort. Methods: The NAILED (Nurse-based Age-independent Intervention to Limit Evolution of Disease) ACS trial is a prospective randomized controlled trial. All eligible patients admitted for ACS were randomized to usual follow-up by a general practitioner or telephone follow-up by study nurses. The intervention was made by continuous telephone contact, with counseling on healthy living and titration of medicines to reach target values for blood pressure and blood lipids. Exclusion criteria were limited to physical inability to follow the study design or participation in another study. Results: A total of 907 patients were assessed for inclusion. Of these, 661 (72.9 %) were included and randomized, 100 (11 %) declined participation, and 146 (16.1 %) were excluded. The main reasons for exclusion were participation in another trial, dementia, and advanced disease. "Excluded" and "declining" patients were significantly older with more co-morbidity, decreased functional status, and had more seldom received education above compulsory school level than "included" patients. Non-participants had a higher 1-year mortality than participants. Conclusions: Nurse-led telephone-based follow-up after ACS can be applied to a large proportion in an unselected clinical setting. Reasons for non-participation, which were associated with increased mortality, include older age, multiple co-morbidities, decreased functional status and low level of education.