Long-term, telephone-based follow-up after stroke and TIA improves risk factors: 36-month results from the randomized controlled NAILED stroke risk factor trial.

BACKGROUND: Strategies are needed to improve adherence to the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level recommendations after stroke and transient ischemic attack (TIA). We investigated whether nurse-led, telephone-based follow-up that included medication titration was more efficient than usual care in improving BP and LDL-C levels 36 months after discharge following stroke or TIA. METHODS: All patients admitted for stroke or TIA at Östersund hospital that could participate in the telephone-based follow-up were considered eligible. Participants were randomized to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C were measured one month after discharge and yearly thereafter. Intervention group patients who did not meet the target values received additional follow-up, including lifestyle counselling and medication titration, to reach their treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). The primary outcome was the systolic BP level 36 months after discharge. RESULTS: Out of 871 randomized patients, 660 completed the 36-month follow-up. The mean systolic and diastolic BP values in the intervention group were 128.1 mmHg (95% CI 125.8-130.5) and 75.3 mmHg (95% CI 73.8-76.9), respectively. This was 6.1 mmHg (95% CI 3.6-8.6, p < 0.001) and 3.4 mmHg (95% CI 1.8-5.1, p < 0.001) lower than in the control group. The mean LDL-C level was 2.2 mmol/L in the intervention group, which was 0.3 mmol/L (95% CI 0.2-0.5, p < 0.001) lower than in controls. A larger proportion of the intervention group reached the treatment goal for BP (systolic: 79.4% vs. 55.3%, p < 0.001; diastolic: 90.3% vs. 77.9%, p < 0.001) as well as for LDL-C (69.3% vs. 48.9%, p < 0.001). CONCLUSIONS: Compared with usual care, a nurse-led telephone-based intervention that included medication titration after stroke or TIA improved BP and LDL-C levels and increased the proportion of patients that reached the treatment target 36 months after discharge. TRIAL REGISTRATION: ISRCTN Registry ISRCTN23868518 (retrospectively registered, June 19, 2012).

One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010: An Observational Study.

BACKGROUND AND PURPOSE: Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations. METHODS: Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence. RESULTS: Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age >75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with ß-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke. CONCLUSIONS: The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment.

Cardiovascular secondary prevention in high-risk patients: a randomized controlled trial sub-study.

BACKGROUND: Enhanced cardiovascular secondary preventive follow-up is needed to improve adherence to recommended low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) levels. Patients with diabetes mellitus (DM) or chronic kidney disease (CKD) have a high risk of recurrent events. Secondary prevention is therefore essential in these patients. METHODS: Patients with acute coronary syndrome, stroke, or transient ischemic attack were randomized to nurse-based telephone follow-up (intervention) or usual care (control). LDL-C and BP were measured at 1 month (baseline) and 12 months post-discharge. Intervention patients with above-target values at baseline received medication titration to achieve treatment goals. Values measured for control patients were given to the patient's general practitioner for assessment. RESULTS: The final analyses included 225 intervention and 215 control patients with DM or CKD. Among patients with above-target baseline values, the following 12-month values were recorded for intervention and control patients, respectively: LDL-C, 2.2 versus 3.0 mmol/L (p < 0.001); and median systolic BP (SBP), 140 versus 145 mmHg (p = 0.26). Among patients with above-target values at baseline, 52.3 % of intervention patients reached target LDL-C values at 12 months versus 21.3 % of control patients (absolute difference of 30.9 %, 95 % CI 16.1 to 43.8 %), and there was a non-significant trend of more intervention patients reaching target SBP (49.4 % versus 36.8 %; absolute difference of 12.6 %, 95 % CI -1.7 to 26.2 %). CONCLUSIONS: Cardiovascular secondary prevention with nurse-based telephone follow-up was more effective than usual care in improving LDL-C levels 12 months after discharge for patients with DM or CKD. TRIAL REGISTRATION: ISRCTN registry; ISRCTN96595458 (date of registration 10 July 2011) and ISRCTN23868518 (date of registration 13 May 2012).

Orthostatic hypotension in stroke/TIA patients: Association with new events and the effect of the NAILED intervention.

BACKGROUND: Fear of orthostatic hypotension (OH) and a reported association with an increased risk of cardiovascular (CV) events may limit antihypertensive treatment after stroke/TIA. In the NAILED trial, systematic titration of antihypertensive treatment resulted in lower blood pressure (BP) and reduced the incidence of stroke. Our aim was to assess the association between OH and CV events or death in a stroke/TIA population and the association between group allocation in the NAILED trial and risk of OH during follow-up. METHODS AND FINDINGS: This post-hoc analysis included all patients with complete BP measurement at baseline in the NAILED trial (n = 814). OH was defined as a drop in systolic BP ≥20 or diastolic BP ≥10 mmHg 1 minute after standing from a seated position. The association between OH and a composite of stroke, myocardial infarction, or death was assessed using an adjusted Cox regression model with OH as a time-varying variable. The association between group allocation (intervention vs. control) and OH was assessed using logistic regression. During a mean follow-up of 4.8 years, 35.3% of patients had OH at some point. OH was not significantly associated with the composite outcome (HR: 1.11, 95% CI: 0.80-1.54). Allocation to the intervention group in the NAILED trial was not associated with OH during follow-up (OR: 0.84, 95% CI: 0.62-1.13). CONCLUSIONS: OH was not associated with an increased risk of CV events or death in this stroke/TIA population. Systematic titration of antihypertensive treatment did not increase the prevalence of OH compared to usual care. Thus, OH did not reduce the gains of antihypertensive treatment.

Incidence and predictors of cardiovascular outcomes after acute coronary syndrome in a population-based cohort study.

There is limited data on long-term outcomes after hospitalization for ACS. We aimed to estimate the rate of recurrent cardiovascular events in the long-term, in a population-based, unselected cohort of ACS patients. We included 1379 patients with ACS hospitalized at Östersund hospital 2010-2014 and followed them from the day after discharge to 31 December 2017. The primary endpoint was the unadjusted rate of the composite of CV death, AMI and ischemic stroke. Risk factors for the primary endpoint were assessed in a multivariable Cox proportional hazards regression model. During a median follow-up of 4.7 years, the unadjusted rate of the primary endpoint was 10.3% at 1 year and 28.6% at the end of follow-up. Predictors of increased risk for subsequent events were congestive heart failure, diabetes mellitus, angina pectoris, prior revascularization with PCI or CABG and treatment with diuretics at discharge. Lipid-lowering therapy at discharge and revascularization with PCI or CABG were associated with a lower risk of recurrent events. The risk of recurrent cardiovascular was high at 1 year and continued to be so during the following almost 3 years of median follow-up. Established predictors of cardiovascular risk were confirmed.

Long-term risk of major adverse cardiovascular events following ischemic stroke or TIA.

Data are scarce on long-term outcomes after ischemic stroke (IS) or transient ischemic attack (TIA). In this prospective cohort study, we examined the cumulative incidence of major adverse cardiovascular events (MACE) after IS and TIA using a competing risk model and factors associated with new events using a Cox-proportional hazard regression model. All patients discharged alive from Östersund Hospital with IS or TIA between 2010 and 2013 (n = 1535) were followed until 31 December 2017. The primary endpoint was a composite of IS, type 1 acute myocardial infarction (AMI), and cardiovascular (CV) death. Secondary endpoints were the individual components of the primary endpoint, in all patients and separated in IS and TIA subgroups. The cumulative incidence of MACE (median follow-up: 4.4 years) was 12.8% (95% CI: 11.2-14.6) within 1 year after discharge and 35.6% (95% CI: 31.8-39.4) by the end of follow-up. The risk of MACE and CV death was significantly increased in IS compared to TIA (p-values < 0.05), but not the risk of IS or type 1 AMI. Age, kidney failure, prior IS, prior AMI, congestive heart failure, atrial fibrillation, and impaired functional status, were associated with an increased risk of MACE. The risk of recurring events after IS and TIA is high. IS patients have a higher risk of MACE and CV death than TIA patients.

Nurse-based secondary preventive follow-up by telephone reduced recurrence of cardiovascular events: a randomised controlled trial.

Enhanced follow-up is needed to improve the results of secondary preventive care in patients with established cardiovascular disease. We examined the effect of long-term, nurse-based, secondary preventive follow-up by telephone on the recurrence of cardiovascular events. Open, randomised, controlled trial with two parallel groups. Between 1 January 2010 and 31 December 2014, consecutive patients (n = 1890) admitted to hospital due to stroke, transient ischaemic attack (TIA), or acute coronary syndrome (ACS) were included. Participants were randomised (1:1) to nurse-based telephone follow-up (intervention, n = 944) or usual care (control, n = 946) and followed until 31 December 2017. The primary endpoint was a composite of stroke, myocardial infarction, cardiac revascularisation, and cardiovascular death. The individual components of the primary endpoint, TIA, and all-cause mortality were analysed as secondary endpoints. The assessment of outcome events was blinded to study group assignment. After a mean follow-up of 4.5 years, 22.7% (n = 214) of patients in the intervention group and 27.1% (n = 256) in the control group reached the primary composite endpoint (HR 0.81, 95% CI 0.68-0.97; ARR 4.4%, 95% CI 0.5-8.3). Secondary endpoints did not differ significantly between groups. Nurse-based secondary preventive follow-up by telephone reduced the recurrence of cardiovascular events during long-term follow-up.

Nurse-led, telephone-based secondary preventive follow-up benefits stroke/TIA patients with low education: a randomized controlled trial sub-study.

BACKGROUND: The objective of this study was to analyze the impact of two forms of secondary preventive follow-up on the association between education level and levels of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) after stroke/transient ischemic attack (TIA). METHODS: We included a population-based cohort of 771 stroke and TIA patients randomly assigned (1:1) to secondary preventive follow-up within primary health care (control) or nurse-led, telephone-based follow-up (intervention) between January 1, 2010, and December 31, 2013, as part of the NAILED (nurse-based age-independent intervention to limit evolution of disease) stroke risk factor trial. We compared BP and LDL-C levels 12 months after hospital discharge in relation to education level (low, ≤10 years; high, >10 years) separately for the intervention and control groups. RESULTS: Among controls, systolic BP (SBP) decreased only among the highly educated (-2.5 mm Hg, 95% confidence interval (CI) -0.2 to -4.8), whereas LDL-C increased in the low-education group (0.2 mmol/L, 95% CI 0.1 to 0.3). At 12 months, controls with low education not more than 70 years of age had higher SBP than controls of the same age with high education (5.8 mm Hg, 95% CI 1.0 to 10.6). In contrast, SBP in the intervention group decreased similarly regardless of education level, LDL-C decreased among those with low education (-0.3 mmol/L, 95% CI -0.2 to -0.4) and, in the subgroup not more than 70 years old, low-educated participants had lower LDL-C at 12 months than those with high education (0.3 mmol/L, 95% CI 0.1 to 0.5). CONCLUSIONS: Nurse-led, telephone-based secondary preventive follow-up led to comparable improvements in BP across education groups, while routine follow-up disfavored those with low education. TRIAL REGISTRATION: ISRCTN Registry ISRCTN23868518 , June 19, 2012 - Retrospectively registered.

Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors.

BACKGROUND: Data are lacking on the risk and impact of a serious hemorrhage on the prognosis after ischemic stroke (IS) or transient ischemic attack (TIA). We aimed to estimate the incidence of serious hemorrhage, analyze the impact on mortality, and identify predictors of hemorrhage after discharge from IS or TIA. METHODS AND FINDINGS: All patients admitted to Östersund Hospital for an IS or TIA in 2010-2013 were included (n = 1528, mean age: 75.1 years). Serious hemorrhages were identified until 31st December 2015. Incidence rates were calculated. The impact on mortality (stratified by functional level) was determined with Kaplan-Meier analysis. Non-parametric estimation under the assumption of competing risk was performed to assess the cumulative incidence and predictors of serious hemorrhages. The incidence rates of serious (n = 113) and intracranial hemorrhages (n = 45) after discharge from IS and TIA were 2.48% and 0.96% per year at risk, respectively. Patients with modified Rankin Scale (mRS) scores of 3-5 exhibited 58.9% mortality during follow-up and those with mRS scores of 0-2 exhibited 18.4% mortality. A serious hemorrhage did not affect mortality in patients with impaired functional status, but it increased the risk of death in patients with mRS scores of 0-2. Hypertension was associated with increased risk of serious hemorrhage. CONCLUSIONS: We found that, after discharge from an IS or TIA, serious hemorrhages were fairly common. Impairments in function were associated with high mortality, but serious hemorrhages only increased the risk of mortality in patients with no or slight disability. Improved hypertension treatment may decrease the risk of serious hemorrhage, but in patients with low functional status, poor survival makes secondary prevention challenging.

Intracranial Hemorrhage After Ischemic Stroke: Incidence, Time Trends, and Predictors in a Swedish Nationwide Cohort of 196 765 Patients.

BACKGROUND: Epidemiological data on the risk of intracranial hemorrhage (ICrH) after ischemic stroke are sparse. The aims of this study were to describe incidence, trends over time, and predictors of ICrH within 1 year after ischemic stroke. METHODS AND RESULTS: All patients registered in the Swedish stroke register Riksstroke for 1998 to 2009 were included (n=196 765), and data were combined with the National Patient Register to identify ICrH occurrence. A matched reference population was obtained. Incidence rates and cumulative incidences were calculated. Multivariable regression analyses were used to identify predictors. Analyses were performed separately for the first 30 days and days 31 to 365 after ischemic stroke. The incidence rate was 1.97% per year at risk for the first year (0.13% in the reference population) and 0.85% excluding the first 30 days. Over time, the cumulative incidence increased the first 30 days but decreased over days 31 to 365. Thrombolysis, previous ICrH, atrial fibrillation, and male sex were associated with increased risk of ICrH during the first 30 days. Previous ICrH, increasing age, and male sex were associated with increased risk during days 31 to 365. Statins and antithrombotic treatment did not independently predict ICrH occurrence. CONCLUSIONS: The incidence of ICrH within 1 year after ischemic stroke was ≈2% per year at risk, about 15 times higher compared with the reference population. Over the study period, ICrH risk increased within the first 30 days but decreased thereafter. Previous ICrH, thrombolysis, and male sex affected the risk, whereas an increased use of antithrombotic treatments and statins did not.

Nurse-Led, Telephone-Based, Secondary Preventive Follow-Up after Stroke or Transient Ischemic Attack Improves Blood Pressure and LDL Cholesterol: Results from the First 12 Months of the Randomized, Controlled NAILED Stroke Risk Factor Trial.

BACKGROUND: Enhanced secondary preventive follow-up after stroke or transient ischemic attack (TIA) is necessary for improved adherence to recommendations regarding blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels. We investigated whether nurse-led, telephone-based follow-up was more efficient than usual care at improving BP and LDL-C levels at 12 months after hospital discharge. METHODS: We randomized 537 patients to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C measurements were performed at 1 month (baseline) and 12 months post-discharge. Intervention group patients who did not meet target values at baseline received additional follow-up, including titration of medication and lifestyle counselling, to reach treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). RESULTS: At 12 months, mean systolic BP, diastolic BP and LDL-C was 3.3 (95% CI 0.3 to 6.3) mmHg, 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 compared to controls. Among participants with values above the treatment goal at baseline, the difference in systolic BP and LDL-C was more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1, and 0.6 mmol/L, 95% CI 0.4 to 0.9). A larger proportion of the intervention group reached the treatment goal for systolic BP (68.5 vs. 56.8%, p = 0.008) and LDL-C (69.7% vs. 50.4%, p < 0.001). CONCLUSIONS: Nurse-led, telephone-based secondary preventive follow-up, including medication adjustment, was significantly more efficient than usual care at improving BP and LDL-C levels by 12 months post-discharge. TRIAL REGISTRATION: ISRCTN Registry ISRCTN23868518.

Implementation of telephone-based secondary preventive intervention after stroke and transient ischemic attack - participation rate, reasons for nonparticipation and one-year mortality.

BACKGROUND AND PURPOSE: Patients who experience a stroke or transient ischemic attack (TIA) are known to be at high risk of subsequent vascular events, underscoring the need for secondary preventive intervention. However, previous studies have indicated insufficiency in the implementation of secondary prevention, emphasizing the need to develop effective methods of follow-up. In the present study, we examined the potential of implementing a telephone-based, nurse-led, secondary preventive follow-up in stroke and TIA patients on a population level by analyzing the participation rate, reasons for nonparticipation, and one-year mortality. METHODS: Between January 1, 2010 and December 31, 2011, all patients admitted to Östersund hospital, Sweden, and diagnosed with either stroke or TIA were considered for inclusion into the secondary preventive follow-up. Baseline data were collected at the hospital, and reasons for nonparticipation were documented. Multivariate logistic regression was performed to identify predictors of the patient decision not to participate and to explore independent associations between baseline characteristics and exclusion. A one-year follow-up of mortality was also performed; the survival functions of the three groups (included, excluded, declining participation) was calculated using the Kaplan-Meier estimator. RESULTS: From a total of 810 identified patients, 430 (53.1%) were included in the secondary preventive follow-up, 289 (35.7%) were excluded mainly due to physical or cognitive disability, and 91 (11.2%) declined participation. Age ≥85 years, ischemic and hemorrhagic stroke, modified Rankin scale score >3, body mass index ≥25, congestive heart failure, and lower education level were independently associated with exclusion, whereas lower education level was the only factor independently associated with the patient decision not to participate. Exclusion was associated with a more than 12 times higher risk of mortality within the first year after discharge. CONCLUSION: Population-based implementation of secondary prevention in stroke and TIA patients is limited by the high prevalence of comorbidity and a considerable degree of disability. In our study, a large proportion of patients were unable to participate even in this simple form of secondary preventive follow-up. Exclusion was associated with substantially higher one-year mortality, and education level was independently associated with physical ability as well as the motivation to participate in the secondary preventive follow-up program.

The NAILED stroke risk factor trial (nurse based age independent intervention to limit evolution of disease after stroke): study protocol for a randomized controlled trial.

BACKGROUND: Secondary prevention after stroke and transient ischemic attack (TIA) is essential in order to reduce morbidity and mortality. Secondary stroke prevention studies have, however, been fairly small, or performed as clinical trials with non-representative patient selection. Long-term follow-up data is also limited. A nurse-led follow-up for risk factor improvement may be effective but the evidence is limited. The aims of this study are to perform an adequately sized, nurse-led, long-term secondary preventive follow-up with a population-based inclusion of stroke and TIA patients. The focus will be on blood pressure and lipid control as well as tobacco use and physical activity. METHODS: A randomized, controlled, long-term, population-based trial with two parallel groups. The patients will be included during the initial hospital stay. Important outcome variables are sitting systolic and diastolic blood pressure, LDL cholesterol and total cholesterol. Outcomes will be measured after 12, 24 and 36 months of follow-up. Trained nurses will manage the intervention group with a focus on reaching set treatment goals as soon as possible. The control group will receive usual care. At least 200 patients will be included in each group, in order to reliably detect a difference in mean systolic blood pressure of 5 mmHg. This sample size is also adequate for detection of clinically meaningful group differences in the other outcomes. DISCUSSION: This study will test the hypothesis that a nurse-led, long-term follow-up after stroke with a focus on reaching set treatment goals as soon as possible, is an effective secondary preventive method. If proven effective, this method could be implemented in general practice at a low cost. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23868518.