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Background Patients who experience a stroke or transient ischemic attack (TIA) are at high risk of recurrent stroke, but little is known about temporal trends in unselected populations. Reports of low adherence to recommended treatments indicate a need for enhanced secondary preventive follow-up to achieve the full potential of evidence-based treatments. In addition, socioeconomic factors have been associated with poor health outcomes in a variety of contexts. Therefore, it is important to assess the implementation and results of secondary prevention in different socioeconomic groups.

Aims The aims of this thesis were to assess temporal trends in ischemic stroke recurrence and evaluate the implementation and results of a nurse-led, telephone-based follow-up program to improve blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels after stroke/TIA.

Methods In study I, we collected baseline data for unique patients with an ischemic stroke event between 1998 and 2009 (n=196 765) from the Swedish Stroke Register (Riksstroke). Recurrent ischemic stroke events within 1 year were collected from the Swedish National Inpatient Register (IPR) and the cumulative incidence was compared between four time periods using the Kaplan-Meier survival analysis and the logrank test. Implementation (study II) and 1-year results (study III-IV) for the secondary preventive follow-up were studied in the NAILED (Nurse-based Age-independent Intervention to Limit Evolution of Disease) study. Between 1 Jan 2010 and 31 Dec 2013, the baseline characteristics of consecutive patients admitted to Östersund Hospital for acute stroke or TIA were collected prospectively (n=1776). Consenting patients in a condition permitting telephone-based follow-up were randomized to nurse-led, telephone-based follow-up or follow-up according to usual care. Follow-up was cunducted at 1 and 12 months after discharge and the intervention included BP and LDL-C measurements, titration of medication, and lifestyle counseling. In study II, we analyzed factors associated with non-participation in the randomized phase of the NAILED study, including association with education level. In addition, we compared the 1-year prognosis in terms of cumulative survival between participants and non-participants. In study III, we compared differences in BP and LDL-C levels between the intervention and control groups during the first year of follow-up and, in study IV, in relation to level of education (low, ≤10 years; high, >10 years).

Results The cumulative 1-year incidence of recurrent ischemic stroke decreased from 15.0% to 12.0%. Among surviving stroke and TIA patients, 53.1% were included for randomization, 35.7% were excluded mainly due to physical or cognitive disability, and 11.2% declined participation in the randomized phase. A low level of education was independently associated with exclusion, as well as the patient’s decision to abstain from randomization. Excluded patients had a more than 12-times higher risk of death within 1 year than patients who were randomized. After 1 year of follow-up, the mean systolic BP, diastolic BP, and LDL-C levels were 3.3 mmHg (95% CI 0.3 to 6.3), 2.3 mmHg (95% CI 0.5 to 4.2), and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group than among controls. Among participants with values above the treatment goal at baseline, the differences in systolic BP and LDL-C levels were more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1; 0.6 mmol/L, 95% CI 0.4 to 0.9). In the intervention group, participants with a low level of education achieved similar or larger improvements in BP and LDL-C than participants with a high level of education. In the control group, BP remained unaltered and the LDL-C levels increased among participants with a low level of education.

Conclusion The 1-year risk of ischemic stroke recurrence decreased in Sweden between 1998 and 2010. Nurse-led, telephone-based secondary preventive follow-up is feasible in just over half of the survivors of acute stroke and TIA and achieve better than usual care in terms of BP and LDL-C levels, and equality in BP improvements across groups defined by education level. However, a large proportion of stroke survivors are in a general condition precluding this form of follow-up, and their prognosis in terms of 1-year survival is poor. Patients with a low education level are over-represented within this group and among patients declining randomization for secondary preventive follow-up. 

Background: The number of stroke survivors is growing worldwide, and these patients have an increased risk of new vascular events and death. This risk decreases with secondary treatment medications recommended in guidelines. However, the characteristics of unselected stroke patients differ from patients included in randomized controlled trials (RCTs). Thus, the efficacy of these treatments based on RCT results may not be directly transferable to the patients treated in clinical practice. A treatment may be associated with a higher risk of serious side-effects or less benefit than expected:1) Antithrombotic treatment increases the risk of a serious hemorrhage, a risk that is not well studied in an unselected population with older age and more comorbidities; 2) Treatment of modifiable risk factors after a stroke can be improved. Many patients do not reach treatment targets, which indicates a need for strategies to improve secondary prevention and increase treatment benefit.It is therefore essential to evaluate recommended treatments through studies in a real-world setting.

Aims: The aims of this thesis were to assessincidence, temporal trends, effect on mortality, and factors associated with an increased risk of a serious hemorrhage after ischemic stroke (IS) or transient ischemic attack (TIA); andif a nurse-led, telephone-based intervention including medical titration could improve modifiable risk factors in patients after stroke or TIA.

Methods: In paper I, all patients registered with an IS in the national stroke register Riksstroke during 1998–2009 were studied. The register was combined with the In-Patient Register and a diagnosis of intracranial haemorrhage (ICrH) within 1 year after IS was identified. In paper II, any diagnosis of serious hemorrhage was identified during follow-up up to 2015 in all patients with an IS or TIA diagnosis, 2010–2013, at Östersund hospital. The incidences of ICrH (papers I and II) and all serious hemorrhages (paper II) were calculated. Kaplan–Meier analysis was used to assess any temporal trend in paper I and if a serious hemorrhage affected survival in study II. Cox regression analysis was used in both studies I and II to assess any factor associated with hemorrhage.

In the randomized controlled NAILED stroke trial, all patients with acute stroke or TIA treated at Östersund hospital during 2010–2013 were screened for participation. Patients whose condition permitted a telephone-based follow-up were randomized to either a control group with follow-up according to usual care or to an intervention group with a nurse-led, telephone-based follow-up including titration of medication. Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) were assessed at 1, 12, 24, and 36 months. We assessed the effect of the intervention on mean levels of BP and LDL-C and on the proportion of patients reaching treatment targets at 12 months (Study III) and at 36 months (Study IV). Study III also assessed for interactions between group allocation and measurement levels at baseline with BP and LDL-C at the 12-month follow-up. Study IV also explored temporal trends.

Results: The risk of an ICrH was 1.97% per year at risk, within the first year after IS,  and 0.85% excluding the first 30 days. Between 1998 and 2009, the risk of an ICrH increased during the first 30 days after an IS but decreased during days 31–365. The risk of a serious hemorrhage was 2.48% per year at risk in paper II. It was more common in elderly. The incidence rate was higher in patients discharged with AP compared with RCTs. A hemorrhage increased the risk of death in patients with good functional status but did not affect the already high mortality in patients with impaired functional status. Male sex and previous ICrH were associated with an increased risk of ICrH during the first year after IS, thrombolytic treatment, atrial fibrillation and warfarin were associated with an increased risk in the acute phase. A previous diagnosis of hypertension was associated with an increased risk of all serious hemorrhages. 

The NAILED trial intervention group had a significantly lower mean systolic BP (SBP), diastolic BP (DBP), and LDL-C at 12 and 36 months. The mean SBP at 36 months was 128.1 mmHg (95% confidence interval (CI): 125.8–130.5) in the intervention group, 6.1 mmHg (95% CI: 3.6–8.6; p<0.001) lower than the control group. The interaction analysis at 12 months showed that the effect of the intervention was confined to patients whose values were above the respective targets at baseline and therefore had their medication adjusted. At 36 months, a significantly higher proportion of patients in the intervention group reached treatment targets for SBP, DBP, and LDL-C. The mean differences and differences in proportions reaching treatment target for BP increased during the 36 months of follow-up.

Conclusion: A serious hemorrhage after an IS or TIA is fairly common. It is more common in elderly and patients with impaired functional status. The incidence is higher in patients discharged with AP compared with RCTs. A serious hemorrhage could affect survival in patients with good functional status. The nurse-led, telephone-based intervention including medical titration used in the NAILED stroke trial improved risk factor levels after stroke and TIA, and more patients reached treatment targets. The effect increased over time.