In patients with acute ischemic stroke (AIS) who have a normal lipid profile or LDL <70 mg/dL, should high-intensity statin therapy (e.g., Lipitor 80 mg daily) still be initiated, and what is the associated risk of intracerebral hemorrhage with high-dose statin use?

In patients with acute ischemic stroke (AIS) who have a normal lipid profile or LDL <70 mg/dL, should high-intensity statin therapy (e.g., Lipitor 80 mg daily) still be initiated, and what is the associated risk of intracerebral hemorrhage with high-dose statin use?

Comment by InpharmD Researcher

Limited data suggest that high-intensity statin therapy, such as atorvastatin 80 mg daily, may provide secondary cardiovascular protection after acute ischemic stroke (AIS) in patients without markedly elevated low-density lipoprotein cholesterol (LDL-C), but evidence in those with baseline LDL-C below 70 mg/dL is less clear. Guidelines primarily extrapolate from broader atherosclerotic cardiovascular disease management, emphasizing overall cardiovascular risk and potential benefit from LDL-C reduction rather than targeting a specific LDL threshold. Landmark trials like SPARCL indicate that intensive statin therapy reduces recurrent ischemic events but carries an increased risk of hemorrhagic stroke, particularly in patients with prior hemorrhage or cerebral small vessel disease. Meta-analyses and observational studies reinforce that intensive statins can improve functional and cardiovascular outcomes, yet the absolute risk of intracerebral hemorrhage may rise, with variability depending on statin type and patient population.

Background

According to the 2021 American Heart Association/American Stroke Association (AHA/ASA) guidelines for patients with stroke and transient ischemic attack, atorvastatin 80 mg daily is recommended for individuals with ischemic stroke who have no known coronary heart disease, no major cardiac sources of embolism, and low-density lipoprotein cholesterol (LDL-C) greater than 100 mg/dL. High-intensity statins are defined as therapies capable of reducing LDL-C by 50% or more, whereas moderate-intensity statins reduce LDL-C by approximately 30% to 49%. However, the guidelines do not specify a lipid threshold for selecting statin intensity in all stroke populations, and recommendations for high-intensity statin therapy are generally extrapolated from broader lipid management guidelines for atherosclerotic cardiovascular disease, which prioritize achieving at least a 50% reduction in LDL-C rather than targeting a specific LDL value. Additionally, current clinical practice guidelines do not clearly address the role of statins in patients with stroke without another indication for statin therapy or the potential benefit in patients with baseline LDL-C levels below 70 mg/dL. [1], [2], [3], [4]

The AHA/ASA guideline highlights two randomized controlled trials, Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) and Treat Stroke to Target (TST), that evaluated lipid-lowering therapy after ischemic stroke. In SPARCL, atorvastatin 80 mg daily reduced recurrent ischemic stroke in patients without another established indication for statin therapy; however, post hoc analyses suggested differing effects by stroke subtype, with a reduced risk of ischemic stroke (hazard ratio [HR] 0.78, 95% CI 0.66–0.94) but an increased risk of hemorrhagic stroke (HR 1.66, 95% confidence interval [CI] 1.08–2.55) compared with placebo. The TST trial further demonstrated that targeting an LDL-C <70 mg/dL was superior to a target of 90–110 mg/dL for preventing major cardiovascular events after stroke. The panel notes that these trials did not include patients with cardioembolic stroke in the absence of atherosclerotic disease. Evidence from these stroke-specific trials is further supported by randomized trials in patients with atherosclerotic cardiovascular disease showing benefit from intensive lipid lowering, supporting high-intensity statin therapy in high-risk patients and consideration of additional agents such as ezetimibe or PCSK-9 inhibitors if LDL-C remains ≥70 mg/dL despite maximally tolerated statin therapy. [1,5,6]

The guideline panel also references the 2018 blood cholesterol management guideline, which provides broader recommendations for statin therapy but is not specific to stroke populations. In that guideline, high-intensity statins are recommended for patients with severe primary hypercholesterolemia (LDL-C ≥190 mg/dL), while moderate-intensity statins are recommended for adults aged 40–75 years with diabetes and LDL-C ≥70 mg/dL, or for those without diabetes but with LDL-C ≥70 mg/dL and an elevated 10-year ASCVD risk when treatment is favored after risk discussion. Higher-risk patients may reasonably be started on high-intensity statin therapy to achieve ≥50% LDL-C reduction. These recommendations emphasize that statin intensity decisions are typically based on an overall cardiovascular risk assessment rather than lipid levels alone, although they are not specific to patients with stroke. [7]

Across multiple meta-analyses intensive statin therapy has been associated with improved secondary prevention after acute ischemic stroke (AIS) but demonstrates a nuanced risk–benefit profile. A 2022 meta-analysis of 11 randomized trials involving 20,163 patients found that more intensive LDL-C lowering with statins reduced the risk of recurrent stroke by 12% (RR 0.88, 95% CI 0.80–0.96) and major cardiovascular events by 17%, but increased the risk of hemorrhagic stroke by 46% (RR 1.46, 95% CI 1.11–1.91), with benefits primarily observed in patients with evidence of atherosclerosis. A 2025 systematic review including 53,118 patients similarly reported that intensive statin therapy improved functional outcomes at three months (modified Rankin Scale 0–2 and 0–3), though intracerebral hemorrhage (ICH) risk was elevated, while stroke recurrence, acute coronary syndrome, and all-cause mortality were not significantly affected. Observational studies provide further context for real-world populations. In a northern China cohort of 62,252 AIS patients, high-intensity statin therapy was associated with increased ICH risk (HR 2.12, 95% CI 1.72–2.62), whereas low- to moderate-intensity therapy reduced ICH risk, and rosuvastatin showed the lowest hemorrhage risk among statins. Analyses of AIS patients undergoing intravenous thrombolysis found no significant association between prior statin use or high-intensity therapy and symptomatic ICH or poor outcomes, though unadjusted analyses suggested a trend toward improved functional outcomes with high-intensity statins. Finally, a 2017 nationwide South Korean cohort study of 8,001 patients demonstrated that good adherence to statins after AIS significantly reduced composite adverse outcomes (recurrent stroke, MI, or all-cause mortality), and high-intensity therapy provided additional risk reduction (HR 0.48 versus low-intensity) without increasing hemorrhagic stroke risk. These data suggest that intensive statin therapy after ischemic stroke can improve functional and cardiovascular outcomes, particularly in patients with atherosclerotic risk, but careful attention to hemorrhagic risk and patient selection is warranted. [8], [9], [10], [11], [12]

Additionally, a 2026 study highlights that statins reduce ischemic cardiovascular events, estimating that for every 1,000 stroke patients treated, there are 40 fewer ischemic major cardiovascular events and 6 additional hemorrhagic strokes, indicating a net benefit of therapy. Statins may be combined with ezetimibe or PCSK9 inhibitors when targets are not achieved, but their antithrombotic and fibrinolytic properties can increase hemorrhagic stroke risk. Post hoc analyses from the SPARCL trial and related meta-analyses show that this risk is highest in patients with prior hemorrhagic stroke or cerebral small vessel disease, although the overall reduction in ischemic events supports continued use. [13], [14]

A retrospective observational study analyzed data from 535 patients with first-ever cardioembolic stroke, classified into non-statin (n= 295), low-potency statin (n= 125), and high-potency statin groups (n= 115). The mean duration of follow-up was 22.2 months. Forty patients experienced a recurrent stroke: 29 in the non-statin group, 12 in the low-potency group, and 7 in the high-potency group. Kaplan-Meier estimation demonstrated both statin groups were associated with reduced mortality (log-rank test; p= 0.006). There was no difference in survival between the statin groups and no significant benefit in stroke recurrence was seen with statin therapy. Of note, the baseline LDL-cholesterol in all groups was > 70 mg/dL (mean 87.51, 106.83, and 112.34 respectively). [15]

A 2014 retrospective analysis assessed 1602 patients registered in the Athens Stroke Registry (between January 2000 and December 2011) with atrial fibrillation (AF)-related stroke, including cardioembolic stroke, and no history of coronary artery disease (CAD) nor clinically manifest peripheral artery disease (PAD). Among 1602 stroke patients, 404 (25.2%) with AF-related stroke were included in the analysis, of whom 102 (25.2%) were discharged on statin (regimens unspecified). The supplemental table shows a mean LDL cholesterol level of 133.1 ± 47.7 mg/dL and 117.5 ± 37.0 mg/dL on admission in the statin and non-statin group, respectively. Yet, the specifics on the subtypes of AF-related stroke for statin recipients are not detailed; thus, those specifically with cardioembolic stroke could not be quantified. Overall, the results showed statin treatment was independently associated with lower mortality (HR 0.49, 95% CI 0.26–0.92) and lower risk for the composite cardiovascular (CV) endpoint during the median 22 months follow-up (HR 0.44, 95%CI 0.22–0.88), but not with stroke recurrence (HR 0.47, 95%CI 0.22–1.01, p= 0.053). [16]

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-4 for your response.

High-intensity versus moderate-intensity statin treatment for patients with ischemic stroke: Nationwide cohort study
Design	Population-based, active-comparator, cohort study N= 27,387
Objective	To examine the effectiveness and safety outcomes among patients initiating high-intensity versus moderate-intensity statins after ischemic stroke
Study Groups	Moderate-intensity (n= 14,355) High-intensity (n= 13,032)
Inclusion Criteria	Age 18 years or older, first-time ischemic stroke, redeemed a statin prescription 21 days after stroke admission
Exclusion Criteria	Used statin prior to first ischemic stroke, low-intensity statins, use of statins a year prior to the date of hospital admission, death or recurrent stroke before the cohort study
Methods	The Danish Stroke registry was used to identify patients with first-time ischemic stroke during 2012-2021 and classified patients as high or moderate-intensity statin users based on prescription redeemed. The 5-year risk difference (RD) and Cox proportional hazards regression were calculated to determine the 5-year hazard ratio (HR) of outcome measures.
Duration	January 1, 2012 to December 31, 2018
Outcome Measures	Effectiveness outcome: 5-year risk for stroke recurrence, myocardial infarction, heart failure, venous thromboembolism, all-cause mortality Safety outcome: 5-year risk for developing diabetes, liver disease, kidney disease
Baseline Characteristics		Moderate-intensity (n= 14,355)	High-intensity (n= 13,032)
	Age, years	69	69
	Female	44.9%	47.8%
	LDL, mmol/L	3.30	3.40
	Comorbidities Transient ischemic attack Atrial fibrillation or flutter Hypertension Diabetes Heart valve disease Venous thromboembolism Endocariditis Myocarditis or pericarditis Heart failure Cardimyopathy Tachyarrhythmia Rare risk factors for stroke	2.4% 13.2% 56.4% 8.0% 3.4% 3.0% 0.2% 0.4% 3.1% 0.7% 2.7% 2.1%	2.5% 11.1% 56.7% 8.3% 3.3% 3.3% 0.1% 0.4% 2.9% 0.6% 2.5% 2.7%
Results	Endpoint	Moderate-intensity (n= 14,355)	High-intensity (n= 13,032)	Risk difference (95% confidence interval [CI])	Hazard ratio (95% CI)
	Stroke recurrence	8.3%	9.1%	0.8% (0.1% to 1.4%)	1.08 (0.96 to 1.22)
	Myocardial infarction	1.6%	1.7%	-0.1% (-0.2% to 0.4%)	1.03 (0.77 to 1.38)
	Heart failure	3.6%	3.7%	0.1% (-0.3% to 0.5%)	1.04 (0.87 to 1.25)
	Venous thromboembolism	1.1%	0.8%	-0.3% (-0.5% to -0.1%)	0.78 (0.53 to 1.14)
	All-cause mortality	18.3%	17.2%	-1.1% (-0.1% to -2.1%)	0.93 (0.85 to 1.01)
	Diabetes	11.6%	12.8%	1.2% (0.4% to 1.9%)	1.10 (1.00 to 1.21)
	Liver disease	1.0%	0.7%	-0.3% (-0.5% to -0.2%)	0.72 (0.51 to 1.04)
	Kidney disease	2.9%	2.8%	-0.1% (-0.4% to 0.2%)	0.99 (0.81 to 1.22)
Adverse Events	See above
Study Author Conclusions	Compared with initiation of moderate-intensity statins, initiation of high-intensity statins after ischemic stroke was associated with similar risks of most effectiveness and safety outcomes. However, mortality risk was reduced, and diabetes risk was increased.
InpharmD Researcher Critique	The follow-up period was relatively short and an analysis showed that a significant proportion of patients either stopped taking their prescribed statin or switched to a different statin within about a year. Due to these limitations, the observed lack of significant results in the study may not accurately reflect the long-term effects of statins.

References:
[1] Bach F, Skajaa N, Esen BÖ, et al. High-intensity versus moderate-intensity statin treatment for patients with ischemic stroke: Nationwide cohort study. Eur Stroke J. 2023;8(4):1041-1052. doi:10.1177/23969873231193288

Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial
Design	Randomized, open-label, non-inferiority trial N= 3,780
Objective	To establish that adding ezetimibe to moderate-intensity statin could be an effective treatment for lowering cholesterol
Study Groups	Moderate-intensity statin with ezetimibe (n= 1,894) High-intensity statin (n= 1,886)
Inclusion Criteria	Age 19 to 80 years, documented atherosclerotic cardiovascular disease (ASCVD), requiring high-intensity statin, achieving LDL cholesterol concentration of < 70 mg/dL
Exclusion Criteria	Active liver disease or persistent unexplained elevated AST or ALT levels more than two-fold the normal upper limit, solid-organ transplantation recipient, pregnancy/lactation, life expectancy < 3 years
Methods	Patients were randomized to receive either a combination therapy of moderate-intensity statin with ezetimibe (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg).
Duration	February 14, 2017 to December 18, 2018
Outcome Measures	Primary: 3-year composite of cardiovascular death, major cardiovascular events, non-fatal stroke Secondary: Composite of all-cause death, major cardiovascular event, or non-fatal stroke
Baseline Characteristics		Moderate-intensity statin with ezetimibe (n= 1,894)	High-intensity statin (n= 1,886)
	Age, years	64	64
	Female	25%	25%
	Body mass index, kg/m²	25.0	25.1
	Comorbidity Previous myocardial infarction Previous percutaneous coronary intervention Previous coronary bypass graft surgery Acute coronary syndrome Previous ischemic stroke Chronic kidney disease End-stage kidney disease on dialysis Peripheral artery disease Hypertension Diabetes Diabetes with insulin treatment Current smoker	39% 66% 7% 1% 5% 10% 1% 4% 66% 37% 3% 17%	40% 66% 6% 1% 6% 11% 1% 4% 68% 37% 4% 16%
	Mediation for dyslipidemia before randomization High-intensity statin High-intensity statin with ezetimibe Moderate-intensity statin Moderate-intensity statin with ezetimibe Low-intensity statin None	38% 4% 36% 13% < 1% 8%	39% 3% 36% 13% < 1% 8%
	Serum LDL cholesterol concentration, mg/dL	80	80
	Patients with LDL cholesterol concentration < 70 mg/dL	34%	33%
Results	Endpoint	Moderate-intensity statin with ezetimibe (n= 1,894)	High-intensity statin (n= 1,886)	Hazard ratio (95% confidence interval [CI])	p-Value
	Primary composite endpoint	172 (9.1%)	186 (9.9%)	0.92 (0.75 to 1.13)	0.43
	Secondary composite endpoint	186 (9.8%)	197 (10.4%)	0.94% (0.77 to 1.15)	0.94
Adverse Events	Discontinuation or dose reduction due to adverse events occurred in 88 (4.8%) of the moderate-intensity statin group vs 150 (8.2%) in the high-intensity statin group (p< 0.0001)
Study Author Conclusions	Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction.
InpharmD Researcher Critique	The study was an open-label trial which could have led to reporting bias; the lower-than-expected event rates meant the non-inferiority margin allowed for a more generous confidence interval; and comparing individual clinical outcomes of the primary endpoint was difficult due to the small number of events.

References:
[1] [1] Kim BK, Hong SJ, Lee YJ, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 2022;400(10349):380-390. doi:10.1016/S0140-6736(22)00916-3

Statin Treatment in Patients With Stroke With Low‐Density Lipoprotein Cholesterol Levels Below 70 mg/dL
Design	Retrospective analysis of a prospective nationwide registry N= 2,850
Objective	To investigate whether early statin treatment could reduce the risk of early vascular events in patients with first‐ever ischemic stroke with baseline LDL‐C levels <70 mg/dL
Study Groups	Statin (n= 2,115) No statin (n= 735)
Inclusion Criteria	Acute ischemic stroke (within 7 days of onset), including lesion positive with symptoms lasting < 24 hours; and baseline LDL-C levels < 70 mg/dL
Exclusion Criteria	Stroke or other determined or undetermined cause; without information on fasting lipid profiles at admission; history of symptomatic atherothrombotic diseases, including stroke, transient ischemic attack, coronary artery diseases, or peripheral artery diseases; and prior statin treatment
Methods	Demographic, clinical, imaging, and laboratory data were prospectively collected with ischemic stroke subtypes classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria and refined to include information from modern imaging. Lipid profiles were obtained during the first fasting period following admission. Patients were treated according to stroke guidelines with use of antiplatelet and anticoagulants based on indications. Statin therapy was started during hospital stay.
Duration	Data collection: July 2011 to July 2020 Mean follow-up: 91.3 ± 19.9 days
Outcome Measures	Primary: Composite of stroke (hemorrhagic or ischemic), myocardial infarction (MI), and all-cause death with 3 months Secondary: Occurrence of the following individual events within 3 months: 1) all types of stroke, 2) MI, 3) all-cause death, and 4) hemorrhagic stroke
Baseline Characteristics		Total (n= 2,850)	No Statin (n= 735)	Statin (n= 2,115)
	Age, years	69.5 ± 13.4	70.1 ± 13.9	69.3 ± 13.2
	Male	1,810 (63.5%)	448 (61.0%)	1,362 (64.4%)
	Weight, kg	60.8 ± 11.5	59.1 ± 11.7	61.4 ± 11.4
	Body mass index	22.9 ± 3.5	22.3 ± 3.7	23.1 ± 3.4
	Arrival Within 24 hours > 24 hours	1,916 (67.2%) 934 (32.8%)	529 (72%) 206 (28%)	1,387 (65.6%) 728 (34.4%)
	Prestroke modified Rankin Scale 0–1	2,490 (87.4)	630 (85.7%)	1,860 (87.9%)
	Baseline NIHSS score, median (IQR)	4 (2–11)	6 (2–15)	4 (1–9)
	TOAST Large‐artery atherosclerosis Small‐vessel occlusion Cardioembolism	1,132 (39.7%) 543 (19.1%) 1,175 (41.2%)	229 (31.2%) 106 (14.4%) 400 (54.4%)	903 (42.7%) 437 (20.7%) 775 (36.6%)
	Medical history and risk factors Hypertension Diabetes Dyslipidemia Smoking Current Ex-smoker Recent Atrial fibrillation Prior antiplatelet use Prior anticoagulant use Prior antihypertensive use Prior antidiabetic use	1,802 (63.2%) 1,047 (36.7%) 276 (9.7%) 658 (23.1%) 261 (9.2%) 119 (4.2%) 952 (33.4%) 518 (18.2%) 147 (5.2%) 1,416 (49.7%) 832 (29.2%)	437 (59.5%) 240 (32.7%) 37 (5%) 134 (18.2%) 81 (11.0%) 39 (5.3%) 325 (44.2%) 128 (17.4%) 50 (6.8%) 336 (45.7%) 180 (24.5%)	1,365 (64.5%) 807 (38.2%) 239 (11.3%) 524 (24.8%) 180 (8.5%) 80 (3.8%) 627 (29.6%) 390 (18.4%) 97 (4.6%) 1,080 (51.1%) 652 (30.8%)
	Large artery steno‐occlusion No stenosis Mild stenosis (< 50%) Significant stenosis (> 50%) Occlusion	1,238 (43.4%) 196 (6.9%) 497 (17.4%) 919 (32.2%)	328 (44.6%) 32 (4.4%) 81 (11%) 294 (40%)	910 (43%) 164 (7.8%) 416 (19.7%) 625 (29.6%)
	Laboratory findings White blood cell count Platelet count Creatinine Glucose Total cholesterol Triglyceride HDL-C Non-HDL-C LDL-C	8.2 ± 3.6 217.2 ± 84.7 1.10 ± 1.17 147.8 ± 67.6 119.7 ± 25.0 104.7 ± 92.8 43.2 ± 14.8 76.6 ± 22.5 56.6 ± 11.2	8.5 ± 4.4 212.0 ± 85.5 1.20 ± 1.40 149.3 ± 75.7 116.2 ± 23.5 97.6 ± 84.3 41.4 ± 14.7 74.8 ± 20.2 54.8 ± 12.5	8.0 ± 3.2 218.9 ± 84.4 1.07 ± 1.08 147.3 ± 64.5 120.9 ± 25.4 107.2 ± 95.5 43.8 ± 14.8 77.2 ± 23.2 57.2 ± 10.6
	Systolic blood pressure	141.0 ± 26.4	138.2 ± 27.0	142.0 ± 26.1
	Discharge treatment Antidiabetic Antihypertension	691 (24.2%) 1,088 (38.2%)	110 (15%) 198 (26.9%)	581 (27.5%) 890 (42.1%)
Results	Endpoint	No Statin (n= 735)	Event rate at 3 months, % (95% CI)	Statin (n= 2,115)	Event rate at 3 months, % (95% CI)	p-value
	Primary Composite Outcome	373/2,897	13.13% (10.00–16.27)	213/2850	7.64% (6.46–8.82)	< 0.001
	Secondary Outcomes Stroke All-Cause Death Myocardial infarction Hemorrhagic stroke	59/2,897 343/2,897 11/2,897 2/2,897	2.09% (1.00–4.36) 12.13% (9.09–15.17) 0.38% (0.09–1.55) 0.09% (0.00–2.00)	67/2,850 153/2,850 5/2,850 3/2,850	2.37% (1.31–4.30) 5.51% (4.50–6.53) 0.18% (0.01–2.47) 0.10% (0.01–1.60)	0.692 < 0.001 0.263 0.885
	97.5% of patients completed the 3-month follow-up. Subgroup analysis reported significant interactions; those with higher NIHSS scores (> 4), large-artery occlusion, and cardioembolism subtype on TOAST had substantial reduction in the primary outcomes with statin treatment.
Adverse Events	Not disclosed beyond outcome measures
Study Author Conclusions	In this study, early statin treatment reduced the risk of 3‐month composite stroke, MI, and all‐cause death but did not alter the risk of stroke recurrence in patients with first‐ever ischemic stroke with baseline LDL‐C levels <70 mg/dL. Further study to confirm the results would be warranted for patients with acute ischemic stroke.
InpharmD Researcher Critique	While the study included all forms of acute stroke, roughly 40% of all patients suffered from cardioembolism. A subanalysis of this specific patient population was not performed. Due to the retrospective design and lack of randomization, bias is inevitable and confounding stroke risks may have occurred. Although this was a large study, it was limited to hospitals in South Korea with data collection spanning many years when treatment standards may have changed.

References:
[1] [1] Kim JT, Lee JS, Kim BJ, et al. Statin Treatment in Patients With Stroke With Low-Density Lipoprotein Cholesterol Levels Below 70 mg/dL. J Am Heart Assoc. 2023;12(18):e030738. doi:10.1161/JAHA.123.030738

Statin Therapy in Acute Cardioembolic Stroke with No Guidance-Based Indication
Design	Retrospective, observational study N= 6,124
Objective	To determine whether the statin therapy is beneficial in preventing major vascular events in this population
Study Groups	Statin nonuser (n= 1,025) Statin user (n= 1,863)
Inclusion Criteria	Presence of acute ischemic stroke or transient ischemic attack, hospitalized within 7 days of symptom onset
Exclusion Criteria	Patients with an established indication for statin therapy based on 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guidelines
Methods	Patient data were collected from a prospective, multicenter Korean database of stroke patients for analysis.
Duration	Data collection: April 2008 to March 2015
Outcome Measures	Primary: Major vascular event rate at 1 year (stroke recurrence, myocardial infarction, vascular death) Secondary: Subgroup analysis estimating hazard ratio of statin therapy of major vascular events
Baseline Characteristics		Statin nonuser (n= 1,025)	Statin user (n= 1,863)
	Age, years	75.2	75.4
	Male	45.8%	44.0%
	Vascular risk factors History of stroke or TIA Hypertension Diabetes mellitus Dyslipidemia Current smoker	27.2% 69.1% 26.1% 14.9% 11.1%	26.0% 69.6% 24.7% 30.6% 11.5%
	Risk category for cardioembolism Medium risk High risk without atrial fibrillation Atrial fibrillation	4.3% 3.9% 91.7%	9.3% 4.0% 86.7%
	Prestroke statin use	11.8%	19.7%
	LDL-C, mg/dL (interquartile range [IQR])	87.3 (85.3 to 89.2)	96.8 (95.2 to 98.4)
Results	Endpoint	Statin nonuser (n= 1,025)	Statin user (n= 1,863)	p-value
	Major vascular events (95% CI) Stroke recurrence Vascular death All-cause death	20.5% (17.1% to 23.9%) 6.5% (4.2% to 8.9%) 16.5% (13.4% to 19.6%) 35.8% (31.8% to 39.7%)	9.3% (7.8% to 10.8%) 5.1% (4.0% to 6.3%) 5.6% (4.4% to 6.8%) 24.0% (21.8% to 26.1%)	< 0.001 0.301 < 0.001 < 0.001
		HR (95% CI)	p-value
	Statin intensity No statin Low-to-moderate High	Reference 0.37 (0.29 to 0.47) 0.41 (0.30 to 0.56)	-- < 0.001 < 0.001
Adverse Events	N/A
Study Author Conclusions	Starting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin.
InpharmD Researcher Critique	There was limited information on long-term adherence to statin therapy post-discharge and whether physicians continued prescribing statins. Some non-users may have started statins later. Due to the retrospective nature of the study, unmeasured confounding and selection bias cannot be ruled out.

References:
[1] Park HK, Lee JS, Hong KS, et al. Statin therapy in acute cardioembolic stroke with no guidance-based indication. Neurology. 2020;94(19):e1984-e1995. doi:10.1212/WNL.0000000000009397