Atorvastatin + CPAP for Sleep Apnea

Overseen By Sanja Jelic, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Columbia University

Must not be taking: All medications

Disqualifiers: Coronary artery disease, heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

110 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants do not regularly use any medications, so you would need to stop taking your current medications to join.

What data supports the effectiveness of the treatment Atorvastatin + CPAP for Sleep Apnea?

Research shows that CPAP therapy can improve cholesterol levels in patients with sleep apnea, which may help reduce the risk of heart-related issues. Additionally, studies suggest that people who are consistent with taking lipid-lowering drugs like atorvastatin are also more likely to adhere to CPAP therapy, potentially enhancing overall treatment effectiveness. ^{1 2 3 4 5}

Is the combination of Atorvastatin and CPAP therapy safe for humans?

Atorvastatin, also known as Lipitor, is generally considered safe and well-tolerated, with common side effects being mild and related to the digestive system. However, it can cause serious side effects like muscle damage and liver issues, especially when combined with certain other medications. There is no specific safety data available for the combination of Atorvastatin and CPAP therapy. ^{6 7 8 9 10}

How does the drug Atorvastatin differ from other treatments for sleep apnea?

Atorvastatin, commonly used to lower cholesterol, is being studied in combination with CPAP (a machine that helps keep airways open) for sleep apnea, which is unique because it targets inflammation and cholesterol levels, potentially addressing underlying cardiovascular risks associated with sleep apnea. ^{6 10 11 12 13}

What is the purpose of this trial?

This double-blind placebo-controlled parallel group randomized study design will be used to test whether 4 weeks of atorvastatin 10 mg daily reduces levels of inflammatory markers in OSA patients treated with CPAP (standard of care). The purpose of this study is to investigate: 1) whether statins reduce endothelial inflammation and pro-thrombotic conditions in OSA, including in patients adherent to CPAP (Aim 1); and 2) whether statins reduce endothelial inflammation and pro-thrombotic conditions by improving endothelial cholesterol metabolism and trafficking in OSA (Aim 2).

Research Team

Sanja Jelic, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults over 18 newly diagnosed with obstructive sleep apnea (OSA), characterized by frequent interruptions in breathing during sleep. Participants should not have used CPAP therapy before and must not be on regular medications or have a history of serious heart, lung, kidney diseases, diabetes, cancer, muscle issues or smoking recently.

Inclusion Criteria

I have been newly diagnosed with sleep apnea and have not used CPAP.

Exclusion Criteria

I have a history of heart, lung, kidney, rheumatic diseases, diabetes, cancer, muscle issues or I've smoked in the last 5 years.

I regularly take medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin 10 mg daily or placebo for 4 weeks to test its effects on endothelial dysfunction in OSA patients treated with CPAP

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atorvastatin
• Continuous Positive Airway Pressure Therapy
• Placebo

Trial Overview The study tests if taking Atorvastatin (a cholesterol-lowering medication) for four weeks reduces inflammation related to OSA in patients also using CPAP therapy. It's a randomized trial where some get the real medicine while others get a placebo without knowing which one they're receiving.

Participant Groups

Group I: Treatment Active Control 2 Interventions

OSA patients who adhered or did not adhere with CPAP who are randomized to receive atorvastatin 10 mg daily.

Group II: Control Placebo Group 2 Interventions

OSA patients who adhered or did not adhere with CPAP who are randomized to receive placebo daily.

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

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a study of 117 patients on lipid-lowering therapy who started CPAP for obstructive sleep apnea, those with good medication adherence (≥80%) were 1.8 times more likely to use CPAP for at least 4 hours a day compared to those with low adherence.

The association between medication adherence and CPAP use was influenced by marital status, indicating that social factors may also play a role in adherence to both medications and CPAP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to sleep apnea therapy and use of lipid-lowering drugs: a study of the healthy-user effect. Platt, AB., Kuna, ST., Field, SH., et al.[2022]

An 8-year therapy with autoadjusting positive airway pressure (APAP) significantly reduced daytime sleepiness in patients with moderate to severe obstructive sleep apnea (OSA), indicating improved overall sleep quality.

However, the long-term APAP treatment did not lead to significant changes in fasting lipid levels, suggesting that while it benefits sleep apnea symptoms, it may not directly affect cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid profile after long-term APAP in OSA patients. Rebelo, S., Drummond, M., Marques, JA.[2018]

In a study involving 24 men with high cholesterol, lovastatin showed a potential improvement in sleep quality by reducing the number of awakenings compared to placebo, although it did not significantly differ in other sleep parameters.

Pravastatin, on the other hand, was associated with a decline in sleep quality compared to lovastatin, affecting sleep efficiency and increasing wake time, suggesting that lovastatin may be a better option for sleep-related side effects in patients taking statins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia. Partinen, M., Pihl, S., Strandberg, T., et al.[2019]

CPAP treatment for obstructive sleep apnea (OSA) significantly improves cholesterol levels by decreasing total cholesterol and low-density lipoprotein (LDL) while increasing high-density lipoprotein (HDL), based on a meta-regression analysis of 29 studies involving 1,958 subjects.

The analysis showed that while total cholesterol and LDL levels decreased significantly, triglyceride (TG) levels did not show a significant change, indicating that CPAP may specifically target certain aspects of dyslipidemia in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of CPAP treatment for obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis. Nadeem, R., Singh, M., Nida, M., et al.[2022]

Long-term CPAP treatment significantly reduces total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in patients with severe obstructive sleep apnea (OSA), with improvements observed as early as 2 months and sustained over 5 years.

The reduction in TC and LDL-C was more pronounced in younger patients and those with higher body mass index (BMI), while CPAP therapy did not significantly affect triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 5-year continuous positive airway pressure treatment on the lipid profile of patients with obstructive sleep apnea: A pilot study. Simon, B., Gabor, B., Barta, I., et al.[2020]

Atorvastatin is a highly effective statin that significantly lowers LDL and total cholesterol levels, and it is the first statin proven to reduce triglycerides in patients with high triglyceride levels.

In addition to its cholesterol-lowering effects, atorvastatin has beneficial non-lipid effects, such as improving blood vessel function and reducing inflammation, although clinical trial evidence is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin. Wierzbicki, AS.[2019]

Atorvastatin effectively lowers elevated levels of LDL cholesterol and triglycerides in patients with various dyslipidemic disorders, showing tailored efficacy based on the specific lipid abnormalities present in each patient group.

The drug was well-tolerated among 231 patients in the study, with a safety profile comparable to other medications in the same class, indicating it is a safe option for managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A brief review paper of the efficacy and safety of atorvastatin in early clinical trials. Bakker-Arkema, RG., Best, J., Fayyad, R., et al.[2019]

Atorvastatin, while effective in lowering LDL cholesterol and preventing cardiovascular diseases, can lead to serious side effects such as rhabdomyolysis and acute kidney injury, particularly when used with warfarin due to shared metabolic pathways.

A case study of a 66-year-old man highlighted the risks of renal complications and muscle damage from the combination of atorvastatin and warfarin, emphasizing the need for careful monitoring of drug interactions in patients with cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhabdomyolysis due to warfarin and atorvastatin combination therapy in a patient with ischemic heart disease: (A drug interaction). Soliemanabad, SK., Rasouli, K., Zakariaei, Z., et al.[2022]

Atorvastatin, administered at 40 mg daily for 15 days to 16 normolipidemic subjects, resulted in significant reductions in cholesterol levels, including a 48% decrease in LDL cholesterol, demonstrating its efficacy as a lipid-lowering agent.

The study found that atorvastatin was well tolerated and that its lipid-lowering effects were similar regardless of whether it was taken in the morning or evening, which contrasts with other similar medications that are more effective when taken at night.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening. Cilla, DD., Gibson, DM., Whitfield, LR., et al.[2019]

Atorvastatin effectively lowers LDL cholesterol levels by 41% to 61%, depending on the dosage, through its mechanism of inhibiting HMG Co-A reductase, which increases LDL receptors in the liver.

The safety profile of atorvastatin is favorable, with only transient gastrointestinal side effects and rare changes in liver tests or muscle enzymes, making it a viable option for treating various forms of hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atorvastatin (Lipitor)]. Carpentier, Y., Ducobu, J., Sternon, J.[2018]

Atorvastatin is a highly effective statin that significantly reduces low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels in patients with high cholesterol, achieving better results than other statins.

While atorvastatin is generally safe, it can cause mild side effects like gastrointestinal issues and muscle pain, and it may require monitoring for liver enzyme levels, especially due to its metabolism through the CYP3A4 pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor. Malinowski, JM.[2022]

Atorvastatin effectively lowers total cholesterol, LDL-cholesterol, and triglycerides while increasing HDL-cholesterol, making it more effective than other statins in patients with coronary heart disease (CHD).

It is well tolerated with mild and transient side effects, and long-term studies are ongoing to assess its impact on serious cardiac events and mortality, confirming its role as a first-line treatment for various patients at risk for CHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. Malhotra, HS., Goa, KL.[2018]

In a multicenter trial involving 47 patients, atorvastatin significantly reduced levels of harmful lipoproteins and triglycerides after 12 weeks at both 10 mg and 20 mg doses, indicating its efficacy in managing cholesterol and triglyceride levels.

Atorvastatin not only lowered bad cholesterol (LDL-C) and triglycerides but also increased good cholesterol (HDL-C), making it a promising treatment option for patients with different types of lipid disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels. Alaupovic, P., Heinonen, T., Shurzinske, L., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adherence to sleep apnea therapy and use of lipid-lowering drugs: a study of the healthy-user effect. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Lipid profile after long-term APAP in OSA patients. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of CPAP treatment for obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effect of 5-year continuous positive airway pressure treatment on the lipid profile of patients with obstructive sleep apnea: A pilot study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Atorvastatin. [2019]

7. Ireland pubmed.ncbi.nlm.nih.gov

A brief review paper of the efficacy and safety of atorvastatin in early clinical trials. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Rhabdomyolysis due to warfarin and atorvastatin combination therapy in a patient with ischemic heart disease: (A drug interaction). [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening. [2019]

10. Belgium pubmed.ncbi.nlm.nih.gov

[Atorvastatin (Lipitor)]. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. [2018]

13. Ireland pubmed.ncbi.nlm.nih.gov

Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels. [2019]