Statins After Stroke

(SATURN Trial)

Overseen By Magdy Selim, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Beth Israel Deaconess Medical Center

Must be taking: Statins

Must not be taking: PCSK9 inhibitors

Disqualifiers: Recent myocardial infarction, Diabetes, Severe dementia, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 24 months

1456 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether individuals who have experienced a lobar intracerebral hemorrhage (ICH) should continue taking statins, a common cholesterol-lowering medication. Researchers aim to determine if continuing or stopping statins affects the risk of another ICH and whether genetics influence this decision. Additionally, the trial uses MRI scans to explore how statins impact small blood vessel disease in the brain. Suitable participants are those aged 50 or older who were taking statins when their ICH occurred. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment validation.

Will I have to stop taking my current medications?

The trial specifically looks at whether to continue or stop taking statin drugs after a stroke, so you may need to change your statin use. The protocol does not mention other medications, so it's unclear if you need to stop any other current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that statins, drugs used to lower cholesterol, are generally safe for most people. However, concerns exist about their use in individuals who have experienced an intracerebral hemorrhage (ICH), a type of stroke caused by brain bleeding. Some studies suggest that statins might increase the risk of another ICH, but the evidence remains unclear.

One study found that statins did not significantly increase the risk of ICH compared to a placebo. In simpler terms, people taking statins did not have a much higher chance of brain bleeding than those not taking them. Another study noted a slight increase in brain bleeding risk, but it wasn't enough to be very concerning.

While serious side effects from statins are rare, considering the potential risks and benefits is important, especially for those with a history of ICH. Prospective trial participants should discuss these findings with their doctor to understand their relevance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using statins after a stroke because it's a novel approach to a common issue. Typically, after an intracerebral hemorrhage (ICH), patients discontinue statins due to the risk of bleeding. However, statins are known for their ability to lower cholesterol and may offer protective benefits for the brain. This trial is exploring whether continuing statins after a stroke could prevent further strokes and improve recovery, providing potential benefits beyond the standard post-stroke care, which usually involves stopping these medications.

What evidence suggests that statins might be an effective treatment after a stroke?

Research has shown that statins, a type of medication, can aid recovery after a stroke caused by bleeding in the brain, known as an intracerebral hemorrhage (ICH). Studies have found that both low and high doses of statins improve recovery and daily functioning after an ICH. Importantly, research indicates that statins do not significantly increase the risk of another ICH. While some studies suggest a slight increase in bleeding risk, statins still offer benefits for overall survival and recovery. In this trial, one group of participants will continue taking the same statin agent and dose used at the time of ICH onset, while another group will discontinue their statin use. These findings suggest that continuing statin use after an ICH could benefit many patients. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals aged 50 or older who experienced a type of stroke called spontaneous lobar intracerebral hemorrhage (ICH), were taking statins at the time, and can decide within 7 days to continue or stop their statin medication. It's not for those with severe dementia, high ICH scores, recent heart issues, certain muscle/liver conditions, familial cholesterol problems, drug/alcohol dependency, other serious health issues or women who could become pregnant.

Inclusion Criteria

You have had a specific type of bleeding in your brain confirmed by a CT or MRI scan.

I agree to possibly restart or stop my statin medication as part of the study.

I am 50 years old or older.

Exclusion Criteria

I am taking PCSK9 inhibitors for my cholesterol.

Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, or other obvious reasons for noncompliance, such as unable to adhere to the protocol specified visits/assessments

My brain bleed might be due to another health issue like a tumor or injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Testing

Participants undergo baseline testing for APOE genotype and MRI for a subset

1 week

1 visit (in-person)

Treatment

Participants are randomized to either continue or discontinue statin therapy

24 months

Regular follow-up visits

Follow-up

Participants are monitored for recurrent symptomatic ICH or major adverse cerebro-/cardio-vascular events

24 months

Regular follow-up visits

MRI Study (optional)

A subset of participants undergoes a repeat MRI to evaluate effects on cerebral small vessel disease markers

End of follow-up period

What Are the Treatments Tested in This Trial?

Interventions

• Statins

Trial Overview The SATURN trial is testing whether patients with ICH should keep taking statins or stop them. It also looks into how an individual's APOE genotype might influence this decision. Part of the study includes MRI scans to see how these choices affect brain markers related to small vessel disease and risk of another ICH.

How Is the Trial Designed?

Group I: No-statin Active Control 1 Intervention

Subjects will discontinue the statin agent that they were taking at the time of ICH onset. No placebo will be prescribed for these subjects.

Group II: Statin Active Control 1 Intervention

The same statin agent and dose that subjects were using at the time of ICH onset.

Statins is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Statins for:

• Hypercholesterolemia
• Prevention of cardiovascular events
• Primary prevention of coronary heart disease

Approved in United States as Statins for:

• Hypercholesterolemia
• Prevention of cardiovascular events
• Primary prevention of coronary heart disease
• Secondary prevention of coronary heart disease

Approved in Canada as Statins for:

• Hypercholesterolemia
• Prevention of cardiovascular events
• Primary prevention of coronary heart disease

Approved in Japan as Statins for:

• Hypercholesterolemia
• Prevention of cardiovascular events

Approved in China as Statins for:

• Hypercholesterolemia
• Prevention of cardiovascular events

Approved in Switzerland as Statins for:

• Hypercholesterolemia
• Prevention of cardiovascular events

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Regions Hospital

Collaborator

Trials

3

Recruited

1,900+

UMass Memorial Health

Collaborator

Trials

4

Recruited

970+

St. Mary's Medical Center

Collaborator

Trials

4

Recruited

1,700+

NINDS Stroke Trials Network (StrokeNet)

Collaborator

Trials

2

Recruited

1,600+

Canadian Stroke Consortium (CSC)

Collaborator

Trials

4

Recruited

2,500+

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

MetroHealth Medical Center

Collaborator

Trials

125

Recruited

22,600+

Published Research Related to This Trial

Statins are beneficial for preventing ischemic stroke and should be started as soon as patients can safely take oral medication after passing a dysphagia screen, as they may improve outcomes and reduce mortality.

Current guidelines suggest initiating statin therapy before discharge for patients with stroke related to atherosclerosis or high cholesterol, with simvastatin and atorvastatin being effective options based on previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotective effects of statins: evidence from preclinical and clinical studies. Fisher, M., Moonis, M.[2021]

Statins, known for lowering cholesterol levels, have been shown to significantly reduce the risk of acute ischemic events like myocardial infarction and stroke, highlighting their importance in cardiovascular health.

Recent findings suggest that statins also have direct anti-atherosclerotic effects, improving outcomes in ischemic stroke by reducing carotid plaque vulnerability and enhancing neuroprotection, which may lead to new applications in preventing cardiovascular complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statins in the treatment of acute ischemic stroke. Montecucco, F., Quercioli, A., Mirabelli-Badenier, M., et al.[2019]

In a study of over 2 million patients aged 40 and older, 2.84% were found to be co-medicated with contraindicated drugs while taking CYP3A4-metabolized statins, with simvastatin users having the highest co-medication rate at 4.6%.

Most co-medications (85.3%) occurred when patients received prescriptions from different medical institutions, highlighting a need for better management systems to prevent potential adverse effects from these drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-medication of statins with contraindicated drugs. Yang, BR., Seong, JM., Choi, NK., et al.[2022]

Statins have been proven effective in improving lipid levels and significantly reducing the risk of atherosclerotic coronary artery disease (CAD), which leads to lower morbidity and mortality rates associated with CAD.

While statins are generally well tolerated, there are safety concerns regarding potential adverse effects on muscles, liver, kidneys, and the nervous system, with some risks being well-documented and others remaining speculative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin safety: an overview and assessment of the data--2005. Bays, H.[2022]

A systematic review of 13 randomized trials involving 20,438 participants found that HMG-CoA reductase inhibitors (statins) reduced the risk of stroke by 31%, indicating their efficacy in stroke prevention.

The analysis showed that there were significantly fewer strokes in the treatment group compared to the placebo group, reinforcing the potential of statins to prevent strokes, especially in middle-aged individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stroke, statins, and cholesterol. A meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. Blauw, GJ., Lagaay, AM., Smelt, AH., et al.[2019]

In a study of 143 patients with nonlacunar middle cerebral artery infarcts, those taking statins prior to their ischemic stroke tended to have smaller infarct volumes, suggesting a potential neuroprotective effect of statins.

Multivariable analysis indicated that statin use, along with patient age and recent transient ischemic attack, was independently associated with smaller infarct sizes, highlighting the importance of statins in stroke management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin use is independently associated with smaller infarct volume in nonlacunar MCA territory stroke. Shook, SJ., Gupta, R., Vora, NA., et al.[2006]

In a study of 83 patients with intracerebral hemorrhage (ICH), pre-ICH use of statins did not significantly affect functional independence rates or mortality after 90 days, with similar outcomes for both statin users and non-users.

Only 24% of the patients were using statins before their ICH, and the analysis showed no beneficial or harmful impact of statin use on recovery or survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes from intracerebral hemorrhage among patients pre-treated with statins. Romero, FR., Bertolini, Ede F., Veloso, VN., et al.[2019]

In a phase 1B study involving 33 patients, lovastatin was safely administered at doses up to 8 mg/kg/day within 24 hours after an acute ischemic stroke, with only mild and transient liver enzyme elevations observed.

The study suggests that lovastatin at higher doses than currently approved is feasible and indicates a maximum tolerated dose of 8 mg/kg/day, warranting further research to evaluate its efficacy in improving stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose lovastatin for acute ischemic stroke: results of the phase I dose escalation neuroprotection with statin therapy for acute recovery trial (NeuSTART). Elkind, MS., Sacco, RL., Macarthur, RB., et al.[2022]

Simvastatin is found to be twice as potent as lovastatin and pravastatin on a milligram-per-milligram basis, making it a strong option for lowering cholesterol levels.

Pravastatin is recommended as the preferred choice for patients requiring higher doses due to its lower incidence of myopathy, especially in posttransplant patients receiving cyclosporine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Hsu, I., Spinler, SA., Johnson, NE.[2018]

Rosuvastatin and pitavastatin are newer statins with improved safety profiles due to their minimal interaction with cytochrome P450 enzymes, which reduces the risk of drug-drug interactions.

The effectiveness and pharmacokinetics of these statins can still be influenced by drug transporters and genetic variations, indicating that individual responses to treatment may vary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetics and drug interactions of the two recently developed statins, rosuvastatin and pitavastatin. Hu, M., Tomlinson, B.[2022]

Statins, which are HMG-CoA reductase inhibitors, have been proven to significantly reduce the risk of vascular-related health issues, such as transient ischemic attacks and strokes, in a large patient population.

The findings highlight the need for further analysis and attention from neurologists regarding the clinical and cost implications of statin use in preventing vascular morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Statins (HMG-CoA reductase inhibitors), cholesterol and stroke]. Marta-Moreno, J., Echeandia, C., Oliveros-Cid, A., et al.[2013]

In a study of 534 hypercholesterolemic patients over 8 weeks, atorvastatin at doses of 10, 20, and 40 mg significantly reduced LDL cholesterol levels more effectively than equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin.

All statin medications, including atorvastatin, showed similar safety profiles with no serious side effects like persistent liver enzyme elevation or muscle inflammation, indicating they are well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Jones, P., Kafonek, S., Laurora, I., et al.[2022]

Patients who started statin therapy after experiencing a stroke had a higher likelihood of being discharged home compared to those who were already on statins before the stroke, with an odds ratio of 2.63.

Both groups of patients (those on statins before and after stroke) were more likely to be discharged home than patients who did not receive statin therapy, indicating a beneficial effect of statins on post-stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre and Post-stroke Use of Statins Improves Stroke Outcome. Moonis, M., Kumar, R., Henninger, N., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39997658/

Association of Statin Therapy with Functional Outcomes ... Conclusions: Both low- and high-intensity statin therapy are associated with improved functional outcomes in ICH and may offer a survival ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1052305725000023

LDL-cholesterol lowering agents (statins and PCSK9 ... The data showed that there was not a significant increased risk of intracerebral hemorrhage for all statins and PCSK-9 inhibitors compared with placebo.

3. ahajournals.org ahajournals.org/doi/10.1161/strokeaha.117.019322

Statin Treatment in Patients With Intracerebral Hemorrhage One randomized clinical trial reported an increased likelihood of early neurological deterioration and worse outcome in acute ischemic stroke ...

4. acc.org acc.org/Latest-in-Cardiology/Articles/2021/08/25/13/00/Fact-or-Fiction-Statins-Increase-the-Risk-of-Hemorrhagic-Stroke

Fact or Fiction: Statins Increase the Risk of Hemorrhagic ... The authors conclude that statins may modestly increase the risk of HS while PCSK9i do not. Furthermore, this risk is amplified in a dose-dependent manner.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21755120/

Outcomes from intracerebral hemorrhage among patients ... Results: Statins were used by 20 out of 83 patients (24%) before ICH onset. There was no effect from pre-ICH statin use on functional independence rates (28% ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4841406/

Management of intracerebral hemorrhage–use of statins - PMC This review evaluates the pharmacologic effects of statin therapy and describes how these effects translate to both risks and benefits in ICH.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3158138/

Should Statins be Avoided after Intracerebral Hemorrhage? Although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of intracerebral hemorrhage (ICH) associated with ...

8. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.107.508861?doi=10.1161/STROKEAHA.107.508861

Effect of Statins on Intracerebral Hemorrhage Outcome and ... Pre-ICH statin use was associated with a nonsignificant 19% increase in ICH volume on admission CT (95% CI −7% to +51%, P=0.16) in a linear regression model ...