Rivaroxaban + Atorvastatin for Heart Attack Risk

Overseen By Nathaniel Smilowitz

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: NYU Langone Health

Must be taking: Direct oral anticoagulants, High-intensity statins

Must not be taking: Moderate statins, High-intensity statins

Disqualifiers: Hemorrhagic disorder, End stage kidney disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this pilot study is to assess enrollment feasibility of a randomized trial of direct oral anticoagulant and high-intensity statin therapy versus usual care in patients with Myocardial Injury after Noncardiac Surgery (MINS). The primary aims of this study are to assess feasibility, study drug adherence, and optimize study design (entry criteria, study endpoints, sample size calculation, site selection) and recruitment strategies for the future multicenter randomized clinical trial studying biomarker-based care in post-operative patients at elevated cardiovascular (CV) risk.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are already on a moderate or high-intensity statin, you cannot participate. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of Rivaroxaban and Atorvastatin for reducing heart attack risk?

Research shows that combining low-dose Rivaroxaban with aspirin significantly reduces the risk of heart attacks, strokes, and other major cardiovascular events in patients with stable coronary artery disease. Although Atorvastatin is not directly mentioned in the studies, it is commonly used to lower cholesterol and reduce heart attack risk, suggesting that combining it with Rivaroxaban could be beneficial. ^{1 2 3 4 5}

Is the combination of Rivaroxaban and Atorvastatin safe for humans?

Rivaroxaban has been shown to have a generally favorable safety profile, with a lower risk of fatal bleeding compared to some other blood thinners, although it may increase the risk of certain events in high-risk patients with specific conditions. Atorvastatin is widely used and generally considered safe, but combining it with Rivaroxaban for heart attack risk specifically hasn't been extensively studied, so it's important to consult with a healthcare provider. ^{6 7 8 9 10}

How does the drug combination of Rivaroxaban and Atorvastatin for heart attack risk differ from other treatments?

The combination of Rivaroxaban and Atorvastatin is unique because it combines a blood thinner (Rivaroxaban) with a cholesterol-lowering drug (Atorvastatin) to potentially reduce heart attack risk. This dual approach targets both blood clot prevention and cholesterol management, which is different from treatments that focus on only one of these aspects. ^{6 7 10 11 12}

Research Team

Nathaniel R. Smilowitz, MD, MS

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for patients who have experienced a heart attack after surgery not related to the heart (MINS). It's testing if using Rivaroxaban, an anticoagulant, and Atorvastatin, a statin, can help manage cardiovascular risk better than usual care. Participants must meet certain health criteria to join.

Inclusion Criteria

Ability to provide informed consent

I am 45 years old or older.

I had major surgery not related to the heart and stayed in the hospital overnight within the last 14 days.

Exclusion Criteria

Expected survival <6 months

I have a bleeding disorder.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rivaroxaban 2.5mg twice daily and atorvastatin 80mg daily for 6 months

6 months

Monthly visits for pill count and adherence assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including completion of QOL questionnaires

2 months

2-month and 6-month follow-up visits

Treatment Details

Interventions

• Atorvastatin
• Rivaroxaban

Trial Overview The study compares two approaches: one group will receive Rivaroxaban and high-intensity Atorvastatin therapy while another follows standard post-operative care. The aim is to see if this treatment improves outcomes in those at high CV risk after noncardiac surgery.

Participant Groups

Group I: Rivaroxaban + Atorvastatin Experimental Treatment 2 Interventions

Participants assigned to this arm will receive rivaroxaban 2.5mg twice daily + atorvastatin 80mg daily for 6 months.

Group II: Usual Care Active Control 1 Intervention

Participants assigned to usual care will continue all clinically indicated therapies as prescribed by their treating physicians.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a trial involving 27,395 patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban and aspirin reduced the risk of cardiovascular death, stroke, or heart attack by 24% and decreased overall mortality by 18%.

Rivaroxaban alone did not provide additional benefits compared to aspirin, but the combination therapy also significantly lowered the risk of major limb events, such as amputations, in patients with peripheral artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose rivaroxaban plus aspirin for the prevention of cardiovascular events: an evaluation of COMPASS. Bhagirath, VC., Eikelboom, JW., Anand, SS.[2019]

In a review of five randomized controlled trials involving 26,110 patients, low dose rivaroxaban (2.5 mg twice daily) did not significantly reduce cardiovascular or all-cause mortality in patients with coronary heart disease.

However, it was effective in reducing the risk of myocardial infarction (MI) and stroke, but this benefit came with an increased risk of major bleeding events, highlighting a critical risk-benefit trade-off.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low dose rivaroxaban in patients with coronary heart disease: a systematic review and meta-analysis. Khan, SU., Khan, MZ., Asad, ZUA., et al.[2021]

In a study involving 120 high-risk patients with thrombotic antiphospholipid syndrome, rivaroxaban was found to be associated with a higher rate of thromboembolic events compared to warfarin, with 12% of patients on rivaroxaban experiencing events like ischemic strokes and myocardial infarctions.

The trial, which had a mean follow-up of 569 days, was terminated early due to the increased risk associated with rivaroxaban, indicating that it does not provide a safety or efficacy advantage over warfarin in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Pengo, V., Denas, G., Zoppellaro, G., et al.[2021]

Rivaroxaban, a new oral anticoagulant, shows a favorable safety profile compared to vitamin K antagonists, with no increased risk of major or clinically relevant nonmajor bleeding in a meta-analysis of 23,063 patients across five trials.

Importantly, rivaroxaban is associated with a significant reduction in fatal bleeding events and does not increase the risk of all-cause mortality, suggesting it may be a safer alternative for patients requiring anticoagulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of rivaroxaban and bleeding risk. Wasserlauf, G., Grandi, SM., Filion, KB., et al.[2015]

A large observational study (XANTUS) involving 6784 patients with non-valvular atrial fibrillation confirmed that rivaroxaban is both effective and safe for preventing strokes and other thromboembolic complications in a real-world clinical setting.

Rivaroxaban was associated with a lower risk of fatal intracranial and gastrointestinal bleeding compared to other treatments, highlighting its safety profile in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rivaroxaban at Non-Valvular Atrial Fibrillation: a Prospective Study and Clinical Practice]. Fonyakin, AV.[2019]

Rivaroxaban 2.5 mg twice daily, when combined with aspirin or aspirin plus clopidogrel/ticlopidine, significantly reduced the risk of death from cardiovascular causes, myocardial infarction, or stroke in patients with recent acute coronary syndrome, based on the ATLAS ACS 2-TIMI 51 trial involving a median treatment duration of 13.1 months.

While rivaroxaban showed efficacy in reducing cardiovascular events, it also increased the risk of major bleeding and intracranial hemorrhage compared to placebo, although there was no increase in fatal bleeding, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivaroxaban: a review of its use in acute coronary syndromes. Plosker, GL.[2021]

Rivaroxaban combined with aspirin is more effective in preventing recurrent cardiovascular events than aspirin alone, with an incremental cost-effectiveness ratio (ICER) of €16,522 per quality-adjusted life-year (QALY) gained, based on a lifetime analysis of patients with coronary artery disease (CAD) or peripheral artery disease (PAD).

The cost-effectiveness of the combination therapy was consistent across subgroups, showing ICERs of €8003 for PAD and €18,599 for CAD, indicating that this treatment strategy is economically viable for improving cardiovascular outcomes in these patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in Patients with Coronary and Peripheral Artery Diseases in Italy. Ferrara, P., Cortesi, PA., Di Laura, D., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Low-dose rivaroxaban plus aspirin for the prevention of cardiovascular events: an evaluation of COMPASS. [2019]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Treatment of Patients with Stable Manifestations of Atherosclerotic Vascular Disease: New Possibilities (Conclusion of the Council of Experts from November 16, 2018, Rostov-on-Don)]. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low dose rivaroxaban in patients with coronary heart disease: a systematic review and meta-analysis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Long-Term Treatment with the Combination of Rivaroxaban and Aspirin in Patients with Chronic Coronary or Peripheral Artery Disease: Outcomes During the Open Label Extension of the COMPASS trial. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

[ANMCO Position paper: Evidence and practical indications for the use of low-dose rivaroxaban in stable coronary artery disease and peripheral artery disease]. [2022]

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

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. [2021]

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

Meta-analysis of rivaroxaban and bleeding risk. [2015]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Rivaroxaban at Non-Valvular Atrial Fibrillation: a Prospective Study and Clinical Practice]. [2019]

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

Antithrombotic Therapy for Atrial Fibrillation and Coronary Artery Disease in Patients With Prior Atherothrombotic Disease: A Post Hoc Analysis of the AFIRE Trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Rivaroxaban and risk of myocardial infarction: insights from a meta-analysis and trial sequential analysis of randomized clinical trials. [2015]

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

Rivaroxaban: a review of its use in acute coronary syndromes. [2021]

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

Cost-Effectiveness Analysis of Rivaroxaban Plus Aspirin Compared with Aspirin Alone in Patients with Coronary and Peripheral Artery Diseases in Italy. [2022]