Rosuvastatin for Statin Adverse Reaction Syndrome

Overseen By Gretchen Program Director, RDN, CDCES

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Minneapolis Heart Institute Foundation

Must be taking: Lipid-lowering agents

Disqualifiers: Pregnancy, Severe reactions, others

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

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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if individuals who have had adverse reactions to statins can better tolerate rosuvastatin, a type of statin. Researchers will use a method where participants receive both the actual drug and a placebo (a pill with no active medicine) at different times to compare effects. It is ideal for those who had to discontinue at least two different statins due to side effects and have been off statins for at least 30 days. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to understand how rosuvastatin benefits more patients.

Do I need to stop my current medications to join the trial?

You can continue taking other lipid-lowering medications like ezetimibe and PSCK9 inhibitors if you've been on them for at least a month and are tolerating them well. However, you must have stopped using any statin at least 30 days before joining the trial.

What is the safety track record for rosuvastatin?

Research has shown that rosuvastatin is generally well-tolerated by patients. In a study involving 12,400 patients over several years, rosuvastatin demonstrated a safety profile similar to other statins. Serious muscle injury, such as rhabdomyolysis (a severe muscle breakdown), occurs in less than 0.1% of cases. Serious liver issues are even rarer, occurring in about 0.001% of patients.

However, some people do experience side effects. Studies indicate that 5-30% of individuals might not tolerate statins well, experiencing reactions like muscle pain or weakness. This trial aims to assist those who have had problems with statins before, potentially making rosuvastatin easier to tolerate for them. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Rosuvastatin is unique because it offers a potential solution for patients who experience adverse reactions to other statins, which are commonly used to lower cholesterol and reduce the risk of heart disease. Most statins can cause side effects like muscle pain, but researchers are excited about rosuvastatin because it may have a lower risk of these issues while still effectively managing cholesterol levels. This means it could provide a better quality of life for patients who need cholesterol management but struggle with side effects from current options.

What is the effectiveness track record for rosuvastatin in patients with prior statin intolerance?

Research has shown that rosuvastatin can work well for people who have had problems with other statins. One study found that patients who had issues with other statins experienced a 29% drop in LDL (bad cholesterol) levels when taking rosuvastatin. Another review reported that rosuvastatin lowered LDL cholesterol by 21.7% and reduced inflammation markers by 22.2% over six months. Overall, rosuvastatin has a safety profile similar to other statins, indicating it is generally safe with a comparable chance of side effects. In this trial, participants will receive rosuvastatin in one part of the study and a placebo in the other, allowing researchers to compare the effects directly. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

The DESIFOR-EXPAND trial is for adults over 21 who've had to stop taking at least two different statins due to side effects. They can still be on other cholesterol-lowering meds if they've been stable on them for a month. It's not for those with severe past reactions, women who are pregnant or nursing, or anyone not suited for rosuvastatin.

Inclusion Criteria

I stopped taking statin medication over 30 days ago.

I am 21 or older and had to stop taking at least 2 statins due to side effects.

Exclusion Criteria

Individuals who experienced severe reactions in the past, including rhabdomyolysis, severe myositis, anaphylaxis

I am not prescribed rosuvastatin 20 mg for any health condition.

I am not pregnant, nursing, or trying to get pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blinded N-of-1 Trial

Participants undergo a double-blinded, randomized trial to assess statin intolerance using placebo and rosuvastatin

6 months

Regular visits for monitoring and assessment

Unblinded Treatment

Participants receive 3 months of unblinded rosuvastatin to assess tolerance

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rosuvastatin

Trial Overview This study tests whether patients with previous statin intolerance can tolerate an unblinded dose of Rosuvastatin (Crestor) compared to a placebo. The goal is to see if the n-of-1 trial design helps in managing and understanding individual responses to the drug.

How Is the Trial Designed?

Group I: Placebo taken first, drug taken second Experimental Treatment 2 Interventions

The placebo is assigned to the patient first, with the medication taken in the second part of participation.

Group II: Drug taken first, then placebo taken second Experimental Treatment 2 Interventions

The placebo is assigned to the patient first, with the medication taken in the second part of participation.

Who Is Running the Clinical Trial?

Minneapolis Heart Institute Foundation

Lead Sponsor

Trials

32

Recruited

15,700+

Published Research Related to This Trial

In a study involving 12,400 patients over 12,212 patient-years, rosuvastatin was found to have a safety profile similar to other statins, with adverse events occurring in 57.4% of patients, comparable to 56.8% in the placebo group.

Serious side effects like myopathy and significant liver or muscle enzyme elevations were very rare (less than 0.03% for myopathy), indicating that rosuvastatin is well tolerated among patients with dyslipidemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of rosuvastatin. Shepherd, J., Hunninghake, DB., Stein, EA., et al.[2015]

Rosuvastatin is more effective than other statins like atorvastatin, simvastatin, and pravastatin in significantly lowering LDL cholesterol and total cholesterol levels, as well as triglycerides.

Due to its unique chemical properties, rosuvastatin has a lower risk of muscle toxicity and fewer drug interactions, making it a safer option for patients compared to other statins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of rosuvastatin: a critical risk benefit appraisal and comparison with other antihyperlipidemics. Calza, L.[2021]

Rosuvastatin is a potent statin that significantly reduces LDL cholesterol by 52-63% at doses of 10-40 mg, outperforming other statins like atorvastatin and simvastatin in lowering LDL levels.

It is well tolerated and has a safety profile similar to other statins, making it a suitable option for patients with dyslipidemia, including those with hypertriglyceridemia or diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin--a highly effective new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor: review of clinical trial data at 10-40 mg doses in dyslipidemic patients. Schuster, H.[2017]

Rosuvastatin is the most effective statin for lowering low-density lipoprotein (LDL) cholesterol and has been shown to reduce the risk of cardiovascular events and stabilize atherosclerosis based on prospective, randomized studies.

The review highlights a gap in understanding the efficacy of rosuvastatin in specific patient subpopulations, such as those with chronic kidney disease, women, and various ethnic groups, indicating a need for further research in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the benefits and risks of rosuvastatin therapy. Toth, PP.[2015]

Rosuvastatin is more effective than other statins like atorvastatin and simvastatin in lowering LDL cholesterol levels due to its higher affinity for the enzyme it inhibits, making it a strong option for patients needing significant LDL reduction.

While rosuvastatin can help patients reach LDL goals more quickly and with fewer side effects, it should be used cautiously due to a lack of long-term cardiovascular outcome data compared to other statins, and is recommended primarily for those who cannot tolerate other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin for the treatment of hypercholesterolemia. Culhane, NS., Lettieri, SL., Skae, JR.[2019]

In a large study involving 16,876 patients over 25,670 patient-years, rosuvastatin was found to have a safety profile similar to other statins, with low rates of serious adverse events like myopathy and liver enzyme elevations.

Rosuvastatin was well tolerated across various doses (5-40 mg), and no deaths were attributed to the drug, indicating it is a safe option for treating dyslipidemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of rosuvastatin: update on 16,876 rosuvastatin-treated patients in a multinational clinical trial program. Shepherd, J., Vidt, DG., Miller, E., et al.[2015]

Rosuvastatin, the newest statin approved in the USA, has been shown to have a safety profile similar to other statins, with a low frequency of serious adverse events based on a comprehensive assessment involving over 50,000 patients.

AstraZeneca's ongoing pharmacoepidemiology program includes multiple studies designed to evaluate patient characteristics and safety, ensuring continuous monitoring of rosuvastatin's benefit-risk profile beyond initial clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin safety: a comprehensive, international pharmacoepidemiology programme. Johansson, S., Ming, EE., Wallander, MA., et al.[2016]

Rosuvastatin, the first statin approved after cerivastatin's withdrawal, has a safety profile comparable to other statins at doses up to 40 mg, based on the largest pre-approval database for statins involving extensive clinical trials.

While higher doses (80 mg) of rosuvastatin show increased risks of myopathy and rhabdomyolysis, the incidence rates at lower doses are similar to those of other statins, indicating that careful dose management is crucial for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin safety: lessons from the FDA review and post-approval surveillance. Davidson, MH.[2019]

A study involving over 10,000 veterans found that high-intensity atorvastatin therapy is associated with a higher incidence of adverse drug reactions (ADRs) compared to rosuvastatin, with ADR rates of 4.59% for atorvastatin versus 2.91% for rosuvastatin.

Specific ADRs such as abnormal liver transaminases and muscle symptoms were significantly more common in patients taking atorvastatin, indicating that while both medications are effective, atorvastatin may pose a greater risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of High-Intensity Statins in the Veteran Population: Atorvastatin 40 to 80 mg Compared With Rosuvastatin 20 to 40 mg. Stein, B., Ward, T., Hale, G., et al.[2020]

A novel data-mining approach using relative risk (RR) successfully identified 25 adverse drug reaction (ADR) signals for rosuvastatin among 96,236 elderly outpatients, indicating its potential effectiveness in safety surveillance.

Out of 13 known adverse events exclusive to rosuvastatin, 8 were detected as signals, demonstrating a positive predictive value of 32%, which supports the method's reliability in detecting specific safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signal detection of rosuvastatin compared to other statins: data-mining study using national health insurance claims database. Choi, NK., Chang, Y., Choi, YK., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9757867/

Prevalence of statin intolerance: a meta-analysis - PMC Statin intolerance is associated with suboptimal lipid-lowering therapy and a high risk of first and recurrent CVD events.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1933287411005976

Efficacy and tolerability of once-weekly rosuvastatin in ... One case report identified a mean LDL reduction of 29% in eight patients with previously documented statin adverse events (75% myalgias) who were placed on once ...

3. journal-of-cardiology.com journal-of-cardiology.com/article/S0914-5087(24)00045-5/fulltext

Comprehensive review of statin-intolerance and the ... LDL-C was reduced by 21.7 % and hsCRP was reduced by 22.2 % by the end of 6 months. MACE was lowered by 13 % over a 40.6-month (median) follow- ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCRESAHA.118.312782

Statin Toxicity | Circulation Research More recent data from the FOURIER outcomes study suggests that LDL-c levels can be reduced to <1.03 mmol/L (<40 mg/dL) with statins and PCSK9 ( ...

5. withpower.com withpower.com/trial/rosuvastatin-for-statin-adverse-reaction-syndrome-1554f

Rosuvastatin for Statin Adverse Reaction Syndrome In a study involving 12,400 patients over 12,212 patient-years, rosuvastatin was found to have a safety profile similar to other statins, with adverse events ...

6. ahajournals.org ahajournals.org/doi/10.1161/atv.0000000000000073

Statin Safety and Associated Adverse Events: A Scientific ... The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2090123224005988

Advances in statin adverse reactions and the potential ... Although statins are generally well tolerated, studies have reported that 5–30 % of patients are intolerant to statins [48], [49], which can lead to reduced ...

8. ccjm.org ccjm.org/content/88/7/381

Statin intolerance and new lipid-lowering treatments Statin-intolerant patients who have their medication down-titrated or discontinued are at increased risk of future cardiovascular events. A ...