Association Between Statin Use and Intracerebral Hemorrhage Location

Boe, Nils Jensen; Hald, Stine Munk; Jensen, Mie Micheelsen; Bojsen, Jonas Asgaard; Elhakim, Mohammad Talal; Florisson, Sandra; Saleh, Alisa; Clausen, Anne; Möller, Sören; Harbo, Frederik Severin Gråe; Graumann, Ole; Hallas, Jesper; Rodrı́guez, Luis A. Garcı́a; Salman, Rustam Al-Shahi; Goldstein, Larry B.; Garcı́a-Dorado, David

doi:10.1212/wnl.0000000000201664

Cited by 10 publications

(13 citation statements)

References 56 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We defined spontaneous ICH as ICH not attributable to trauma, hemorrhagic transformation of an IS, or an alternative explanation (eg, tumor, cerebrovascular venous sinus thrombosis, vascular malformations, cavernous hemangiomas, or aneurysms). 14 Using multiple sources, we identified a cohort of all patients 50 years or older hospitalized with first-ever spontaneous ICH (ie, the index ICH) in RSD from January 1, 2009, to December 31, 2018 14 , 15 (eMethods in Supplement 1 ). For each cohort member, we traced all subsequent hospital admissions between the date of the index ICH and the end of the study period (December 31, 2018) that could represent an ICH or IS.…”

Section: Methodsmentioning

confidence: 99%

Major Cardiovascular Events After Spontaneous Intracerebral Hemorrhage by Hematoma Location

et al. 2023

Self Cite

View full text Add to dashboard Cite

ImportanceSurvivors of spontaneous (ie, nontraumatic and with no known structural cause) intracerebral hemorrhage (ICH) have an increased risk of major cardiovascular events (MACEs), including recurrent ICH, ischemic stroke (IS), and myocardial infarction (MI). Only limited data are available from large, unselected population studies assessing the risk of MACEs according to index hematoma location.ObjectiveTo examine the risk of MACEs (ie, the composite of ICH, IS, spontaneous intracranial extra-axial hemorrhage, MI, systemic embolism, or vascular death) after ICH based on ICH location (lobar vs nonlobar).Design, Setting, and ParticipantsThis cohort study identified 2819 patients in southern Denmark (population of 1.2 million) 50 years or older hospitalized with first-ever spontaneous ICH from January 1, 2009, to December 31, 2018. Intracerebral hemorrhage was categorized as lobar or nonlobar, and the cohorts were linked to registry data until the end of 2018 to identify the occurrence of MACEs and separately recurrent ICH, IS, and MI. Outcome events were validated using medical records. Associations were adjusted for potential confounders using inverse probability weighting.ExposureLocation of ICH (lobar vs nonlobar).Main Outcomes and MeasuresThe main outcomes were MACEs and separately recurrent ICH, IS, and MI. Crude absolute event rates per 100 person-years and adjusted hazard ratios (aHRs) with 95% CIs were calculated. Data were analyzed from February to September 2022.ResultsCompared with patients with nonlobar ICH (n = 1255; 680 [54.2%] men and 575 [45.8%] women; mean [SD] age, 73.5 [11.4] years), those with lobar ICH (n = 1034; 495 [47.9%] men and 539 [52.1%] women, mean [SD] age, 75.2 [10.7] years) had higher rates of MACEs per 100 person-years (10.84 [95% CI, 9.51-12.37] vs 7.91 [95% CI, 6.93-9.03]; aHR, 1.26; 95% CI, 1.10-1.44) and recurrent ICH (3.74 [95% CI, 3.01-4.66] vs 1.24 [95% CI, 0.89-1.73]; aHR, 2.63; 95% CI, 1.97-3.49) but not IS (1.45 [95% CI, 1.02-2.06] vs 1.77 [95% CI, 1.34-2.34]; aHR, 0.81; 95% CI, 0.60-1.10) or MI (0.42 [95% CI, 0.22-0.81] vs 0.64 [95% CI, 0.40-1.01]; aHR, 0.64; 95% CI, 0.38-1.09).Conclusions and RelevanceIn this cohort study, spontaneous lobar ICH was associated with a higher rate of subsequent MACEs than nonlobar ICH, primarily due to a higher rate of recurrent ICH. This study highlights the importance of secondary ICH prevention strategies in patients with lobar ICH.

show abstract

Section: Methodsmentioning

confidence: 99%

Major Cardiovascular Events After Spontaneous Intracerebral Hemorrhage by Hematoma Location

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a previous study on statin use and first-ever ICH, however, results obtained by the method we used to establish ICH location were similar to those found when location was based on an anatomical rating scale, CHARTS, 40 by raters masked for clinical data. 16 Using data from the same smaller cohort data as in this study, we reported that the location of the recurrent ICH was largely similar to the index ICH. 41 We also lacked information on brain MRI biomarkers of small vessel disease that may influence prognosis.…”

Section: Discussionmentioning

confidence: 53%

“…We verified the diagnosis of spontaneous first-ever ICH and ascertained hematoma location based on discharge summaries and brain scan reports. 16,30,31 Patients were then followed up until December 31, 2018, with admissions for IS or recurrent ICH verified based on medical records. We linked these data to the same sources for information on potential confounders and medication exposures as in the main study.…”

Section: Additional Analysesmentioning

confidence: 99%

“…Simvastatin was used by 60% of all statin-treated patients in Denmark in 2016 with 35.6% prescribed atorvastatin and 7% rosuvastatin; in 2022, 25.6% of 785,285 Danes (statin users) used simvastatin, 64.5% atorvastatin, and 12.0% rosuvastatin. 12 In addition, the relationship between statin use and the location/etiology of ICH (i.e., lobar vs nonlobar) has been the focus of several studies, [13][14][15][16] yet the location-specific risk of recurrent ICH associated with statin use is uncertain. 3 The primary research question being addressed by this study is whether use of statins after ICH is associated with the risk of any stroke, IS, or recurrent ICH.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association of Statin Use With Risk of Stroke Recurrence After Intracerebral Hemorrhage

Gaist,

García Rodríguez,

Hallas

et al. 2023

Neurology

Self Cite

View full text Add to dashboard Cite

Background and Objectives Survivors of spontaneous intracerebral hemorrhage (ICH) may have indications for statin therapy. The effect of statins on the risk of subsequent hemorrhagic and ischemic stroke (IS) in this setting is uncertain. We sought to determine the risk of any stroke (ischemic stroke, IS or recurrent ICH), IS, and recurrent ICH associated with statin use among ICH survivors. Methods Using the Danish Stroke Registry, we identified all patients admitted to a hospital in Denmark (population 5.8 million) with a first-ever ICH between January 2003 and December 2021 who were aged 50 years or older and survived >30 days. Patients were followed up until August 2022. Within this cohort, we conducted 3 nested case-control analyses for any stroke, IS, and recurrent ICH. We matched controls for age, sex, time since first-ever ICH, and history of prior IS. The primary exposure was statin use before or on the date of subsequent stroke or the equivalent date in matched controls. Using conditional logistic regression, we calculated adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) for any stroke, IS, and recurrent ICH associated with statin exposure. Results We identified 1,959 patients with any stroke (women 45.3%; mean [SD] age, 72.6 [9.7] years) who were matched to 7,400 controls; 1,073 patients with IS (women 42.0%; mean [SD] age, 72.4 [10.0] years) who were matched to 4,035 controls and 984 patients with recurrent ICH (women 48.7%; mean [SD] age, 72.7 [9.2] years) who were matched to 3,755 controls. Statin exposure was associated with a lower risk of both any stroke (cases 38.6%, controls 41.1%; aOR 0.88; 95% CI 0.78–0.99) and IS (cases 39.8%, controls 41.8%, aOR 0.79; 95% CI 0.67–0.92), but was not associated with recurrent ICH risk (cases 39.1%, controls 40.8%, aOR 1.05; 95% CI 0.88–1.24). Discussion Exposure to statins was not associated with an increased risk of recurrent ICH but was associated with a lower risk of any stroke, largely due to a lower risk of IS. Confirmation of these findings in randomized trials is needed. Classification of Evidence This study provides Class III evidence that statin use in patients with ICH is associated with a lower risk of any stroke and IS and not with increased risk of recurrent ICH.

show abstract

“…14–16 The risks of MACE after ICH and ischemic stroke are similar. 17,18 Despite blood pressure-lowering, the annual rate of all MACE for ICH survivors is 4% to 8% in high income countries 9,16,19,20 and ≈10% in lower income countries, 21 resulting in between 826 400 and 2,066 000 MACE each year in ICH survivors worldwide. These ICH survivors who develop MACE are at higher risk of dying than ICH survivors without MACE.…”

Section: Why Antiplatelet Agents?mentioning

confidence: 99%

Antiplatelet Agent Use After Stroke due to Intracerebral Hemorrhage

Al-Shahi Salman,

Greenberg

2023

Stroke

View full text Add to dashboard Cite

This focused update about antiplatelet agents to reduce the high risk of major adverse cardiovascular events after stroke due to spontaneous (nontraumatic) intracerebral hemorrhage (ICH) complements earlier updates about blood pressure-lowering, lipid-lowering, and oral anticoagulation or left atrial appendage occlusion for atrial fibrillation after ICH. When used for secondary prevention in people without ICH, antiplatelet agents reduce the risk of major adverse cardiovascular event (rate ratio, 0.81 [95% CI, 0.75–0.87]) and might increase the risk of ICH (rate ratio, 1.67 [95% CI, 0.97–2.90]). Before 2019, guidance for clinical decisions about antiplatelet agent use after ICH has focused on estimating patients’ predicted absolute risks and severities of ischemic and hemorrhagic major adverse cardiovascular event and applying the known effects of these drugs in people without ICH to estimate whether individual ICH survivors in clinical practice might be helped or harmed by antiplatelet agents. In 2019, the main results of the RESTART (Restart or Stop Antithrombotics Randomized Trial) randomized controlled trial including 537 survivors of ICH associated with antithrombotic drug use showed, counterintuitively, that antiplatelet agents might not increase the risk of recurrent ICH compared to antiplatelet agent avoidance over 2 years of follow-up (12/268 [4%] versus 23/268 [9%]; adjusted hazard ratio, 0.51 [95% CI, 0.25–1.03]; P =0.060). Guidelines in the United States, Canada, China, and the United Kingdom and Ireland have classified the level of evidence as B and indicated that antiplatelet agents may be considered/reasonable after ICH associated with antithrombotic agent use. Three subsequent clinical trials have recruited another 174 participants with ICH, but they will not be sufficient to determine the effects of antiplatelet therapy on all major adverse cardiovascular events reliably when pooled with RESTART. Therefore, ASPIRING (Antiplatelet Secondary Prevention International Randomized Study After Intracerebral Hemorrhage) aims to recruit 4148 ICH survivors to determine the effects of antiplatelet agents after ICH definitively overall and in subgroups.

show abstract

Association Between Statin Use and Intracerebral Hemorrhage Location

Cited by 10 publications

References 56 publications

Major Cardiovascular Events After Spontaneous Intracerebral Hemorrhage by Hematoma Location

Major Cardiovascular Events After Spontaneous Intracerebral Hemorrhage by Hematoma Location

Association of Statin Use With Risk of Stroke Recurrence After Intracerebral Hemorrhage

Antiplatelet Agent Use After Stroke due to Intracerebral Hemorrhage

Contact Info

Product

Resources

About