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Serious hemorrhage and secondary prevention after stroke and TIA
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.ORCID-id: 0000-0002-3542-7966
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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. 

Ort, förlag, år, upplaga, sidor
Umeå: Umeå Universitet , 2018. , s. 63
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1997
Nyckelord [en]
Stroke, transient ischemic attack, intracerebral hemorrhage, intracranial hemorrhage, serious haemorrhage, secondary prevention, modifiable risk factors, randomized controlled trial
Nationell ämneskategori
Neurologi
Forskningsämne
medicin, hjärt- och kärlforskning; invärtesmedicin; neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-153293ISBN: 978-91-7601-982-5 (tryckt)OAI: oai:DiVA.org:umu-153293DiVA, id: diva2:1263690
Disputation
2018-12-13, Hörsal Snäckan, Östersunds sjukhus, Östersund, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2018-11-22 Skapad: 2018-11-16 Senast uppdaterad: 2024-07-02Bibliografiskt granskad
Delarbeten
1. Intracranial Hemorrhage After Ischemic Stroke Incidence, Time Trends, and Predictors in a Swedish Nationwide Cohort of 196765 Patients
Öppna denna publikation i ny flik eller fönster >>Intracranial Hemorrhage After Ischemic Stroke Incidence, Time Trends, and Predictors in a Swedish Nationwide Cohort of 196765 Patients
2015 (Engelska)Ingår i: Circulation. Cardiovascular Quality and Outcomes, ISSN 1941-7713, E-ISSN 1941-7705, Vol. 8, nr 4, s. 413-420Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 approximate to 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.

Nyckelord
epidemiology, intracerebral hemorrhage, intracranial hemorrhage, regression analysis, risk, stroke
Nationell ämneskategori
Kardiologi och kardiovaskulära sjukdomar
Identifikatorer
urn:nbn:se:umu:diva-130286 (URN)10.1161/CIRCOUTCOMES.114.001606 (DOI)000358214000013 ()26152682 (PubMedID)2-s2.0-84937720146 (Scopus ID)
Tillgänglig från: 2017-01-16 Skapad: 2017-01-16 Senast uppdaterad: 2025-02-10Bibliografiskt granskad
2. Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors
Öppna denna publikation i ny flik eller fönster >>Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors
2018 (Engelska)Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0195324Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Public library science, 2018
Nationell ämneskategori
Neurologi
Identifikatorer
urn:nbn:se:umu:diva-147304 (URN)10.1371/journal.pone.0195324 (DOI)000429206800061 ()29621285 (PubMedID)2-s2.0-85045142105 (Scopus ID)
Tillgänglig från: 2018-05-28 Skapad: 2018-05-28 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
3. 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
Öppna denna publikation i ny flik eller fönster >>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
Visa övriga...
2015 (Engelska)Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 10, nr 10, artikel-id e0139997Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Nationell ämneskategori
Kardiologi och kardiovaskulära sjukdomar
Identifikatorer
urn:nbn:se:umu:diva-111483 (URN)10.1371/journal.pone.0139997 (DOI)000363185500019 ()26474055 (PubMedID)2-s2.0-84949033383 (Scopus ID)
Tillgänglig från: 2015-12-01 Skapad: 2015-11-13 Senast uppdaterad: 2025-02-10Bibliografiskt granskad
4. 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
Öppna denna publikation i ny flik eller fönster >>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
2018 (Engelska)Ingår i: BMC Neurology, E-ISSN 1471-2377, Vol. 18, artikel-id 153Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 Ostersund 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 125.8-1305) 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 22 mmol/L in the intervention group, which was 03 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.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2018
Nyckelord
Stroke, TIA, Secondary prevention, Modifiable risk factors, Blood pressure, Cholesterol, Randomized ntrolled study, Telemedicine, Nurses
Nationell ämneskategori
Kardiologi och kardiovaskulära sjukdomar Neurologi
Identifikatorer
urn:nbn:se:umu:diva-152399 (URN)10.1186/s12883-018-1158-5 (DOI)000445259000001 ()30241499 (PubMedID)2-s2.0-85053633739 (Scopus ID)
Forskningsfinansiär
Hjärt-Lungfonden, 20140541
Tillgänglig från: 2018-10-05 Skapad: 2018-10-05 Senast uppdaterad: 2025-02-10Bibliografiskt granskad

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