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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, rivaroxaban (an anticoagulant) and atorvastatin (a cholesterol-lowering drug), to determine if they can lower the risk of heart attacks in individuals who have suffered heart damage after major surgery. The trial aims to assess the feasibility of recruiting enough participants and to optimize the design of a larger future study. Suitable candidates have recently undergone major surgery, are experiencing heart injury afterward, and can provide consent. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

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.

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

Studies have shown that rivaroxaban is generally safe and carries a lower risk of fatal bleeding compared to some other blood thinners. However, taking it with another blood thinner like aspirin can increase the risk of serious bleeding. Atorvastatin, a well-known cholesterol-lowering medication, is usually well-tolerated, with most side effects being mild, such as muscle pain or digestive issues.

The trial is in an early stage, so specific safety information for this combination of treatments is limited. However, both medications have approval for other uses, indicating they are generally safe when used as directed. Participants should consult their doctor about potential risks before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining rivaroxaban and atorvastatin for heart attack risk because this duo targets blood clots and cholesterol simultaneously, a unique approach compared to standard treatments. While typical care might involve drugs that separately manage blood pressure, blood thinning, or cholesterol, this combination has rivaroxaban, a blood thinner, working alongside atorvastatin, a cholesterol-lowering statin. This dual-action may offer enhanced protection against heart attacks by addressing two major risk factors at once.

What evidence suggests that this trial's treatments could be effective for reducing heart attack risk?

Research has shown that taking a low dose of rivaroxaban with aspirin can significantly lower the risk of heart attacks, strokes, and other major heart-related issues. One study found that this combination is more effective at reducing heart problems than aspirin alone. Additionally, rivaroxaban has been linked to a 16% lower risk of death from heart attacks in some cases. In this trial, participants in one arm will receive a combination of rivaroxaban and atorvastatin to evaluate its potential to further reduce heart attack risks. However, the effectiveness of this combination for reducing heart attack risk after non-heart-related surgery is still under investigation. ^{1 2 3 6 7}

Who Is on the Research Team?

Nathaniel R. Smilowitz, MD, MS

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/early-phase-1-myocardial-injury-after-noncardiac-surgery-5-2025-b5058

Rivaroxaban + Atorvastatin for 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11012887/

Efficacy and Safety of Combination Therapy with Low-Dose ... These studies showed that low-dose rivaroxaban 2.5 mg bid (LDR) plus ASA reduced the rate of cardiovascular events compared to the antiplatelet ...

3. bjgp.org bjgp.org/content/75/756/e466

Potential interactions between direct oral anticoagulants ... Effectiveness outcomes included ischaemic stroke, myocardial infarction (MI), VTE, cardiovascular mortality, and all-cause mortality during the follow-up ( ...

4. academic.oup.com academic.oup.com/pmj/advance-article/doi/10.1093/postmj/qgaf163/8267895?searchresult=1

Association between rivaroxaban and the prognosis of ... No significant association was observed between rivaroxaban and clinical outcomes in patients with AMI and new-onset AF. Given the small sample ...

5. clinicaladvisor.com clinicaladvisor.com/news/xarelto-reduces-heart-attack-mortality/

Xarelto reduces heart attack mortality Overall, the rivaroxaban group had a 16% reduced risk for death (HR: 0.84; 95% CI: 0.74 to 0.96; P=0.008), but analysis revealed that the 5 mg ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1538783624005798

Rivaroxaban, in combination with low-dose aspirin, is ... Rivaroxaban, in combination with low-dose aspirin, is associated with a reduction in proinflammatory and prothrombotic circulating vesicle signatures.

7. ashpublications.org ashpublications.org/hematology/article/2020/1/642/474351/Combining-antiplatelet-and-anticoagulant-therapy

Combining antiplatelet and anticoagulant therapy in ... Although each helps reduce thrombotic risk, their combined use significantly increases the risk of major bleeding events, which can be life threatening.