Polypill for Acute Coronary Syndrome

(POLY-ACS Trial)

Overseen By Ambarish Pandey, MD, MSCS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Statins, Aspirin, Clopidogrel, Prasugrel

Must not be taking: Anticoagulants

Disqualifiers: Renal failure, Cardiac support, Pregnancy, 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: 1

Duration: 1 month

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a once-daily "polypill" for individuals who have experienced acute coronary syndrome (ACS) and received a drug-eluting stent (a small tube placed in the heart's arteries). The polypill combines three medications typically taken separately: a statin to lower cholesterol, aspirin to reduce blood clots, and another blood-thinning drug. The researchers aim to determine if this single pill can improve patient adherence to treatment plans and enhance health outcomes. Individuals who have had ACS and a stent placed may be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, if you have a contraindication (reason not to take) to any component of the polypill, you may not be eligible to participate.

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

Research shows that the polypill approach, which combines several medications into one pill, is generally well-tolerated by patients with heart conditions. Previous studies on using a polypill for heart diseases have shown promising safety results. These studies indicate that combining medications like rosuvastatin (which lowers cholesterol), aspirin (which thins the blood), and either clopidogrel or prasugrel (both prevent blood clots) helps people take their medicine more regularly without increasing the risk of serious side effects.

While specific data on side effects for this exact combination in patients with acute coronary syndrome is limited, each component of the polypill is already widely used and approved for treating heart conditions. This suggests that the polypill is likely safe for most patients. However, as with any medication, some risks may still exist, such as muscle pain from rosuvastatin or bleeding from aspirin and the other drugs. Overall, the polypill aims to simplify medication regimens and potentially enhance safety by reducing the number of separate pills needed each day. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for acute coronary syndrome?

Researchers are excited about the polypill for acute coronary syndrome because it combines three essential medications—rosuvastatin, aspirin, and either prasugrel or clopidogrel—into a single, fixed-dose pill. This is different from the standard of care, where patients typically take these medications separately. The polypill simplifies the treatment regimen, potentially improving medication adherence and making it easier for patients to take their medications consistently. By reducing the pill burden, the polypill might enhance the effectiveness of treatment and improve outcomes for those recovering from a heart attack.

What evidence suggests that this trial's treatments could be effective for acute coronary syndrome?

Research has shown that the polypill, which combines several heart medications into one daily pill, could benefit people with acute coronary syndrome (ACS). In this trial, participants in the polypill group will receive a fixed-dose combination that includes rosuvastatin, aspirin, and either prasugrel or clopidogrel. Studies have found that not taking medications as prescribed links to worse heart disease outcomes. The polypill can help by simplifying adherence to treatment plans. One study found that about 84.2% of people believe a polypill could improve heart disease outcomes at the same or lower cost. Overall, the polypill aims to simplify treatment and help patients manage their condition more effectively. ^{1 3 6 7 8}

Who Is on the Research Team?

Ambarish Pandey, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with acute coronary syndrome who've had a stent placed. They must have normal kidney function and no history of bypass surgery, severe heart failure, or need for blood thinners. They can't be allergic to the polypill components (statin, aspirin, clopidogrel/prasugrel) and should not have health issues limiting their life expectancy within a month.

Inclusion Criteria

I had a stent placed in my heart's artery using a minimally invasive procedure.

Exclusion Criteria

You have had a bad reaction to aspirin, prasugrel, or rosuvastatin in the past.

Pregnancy

Your kidney function, measured by a test called estimated glomerular filtration rate, is very low.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a fixed-dose polypill consisting of rosuvastatin, aspirin, and either clopidogrel or prasugrel daily

1 month

Monthly visits for medication adherence assessment

Follow-up

Participants are monitored for adherence to medication and safety after treatment

1 month

1 visit (in-person) for lab draw and adherence assessment

What Are the Treatments Tested in This Trial?

Interventions

• Control treatment
• Polypill

Trial Overview The study compares usual care with a 'polypill' strategy post-stent placement in patients with acute coronary syndromes. The polypill includes rosuvastatin (for cholesterol), aspirin, and clopidogrel/prasugrel (blood thinners). It's designed to improve medication adherence and outcomes.

How Is the Trial Designed?

Group I: Polypill Experimental Treatment 1 Intervention

Patients will be randomized to receiving a fixed-dose polypill in addition to other guideline-directed medical therapies prescribed by their physician. Polypill formulations will include rosuvastatin 40 mg, aspirin 81 mg, and prasugrel 10 mg daily or rosuvastatin 40 mg, aspirin 81 mg, and clopidogrel 75 mg.

Group II: Usual Care (individual medications prescribed by primary cardiologist) Active Control 1 Intervention

Patients will receive usual post-ACS care and medications prescribed by their provider. All of the individual components will be available at low- or no-cost to participants as individual pill formulations.

Control treatment is already approved in European Union for the following indications:

Approved in European Union as Trinomia for:

• Secondary prevention of cardiovascular events in patients who have experienced a myocardial infarction

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Acetylsalicylic acid (aspirin) is the standard treatment for unstable angina pectoris, effectively reducing the risk of death and myocardial infarction by 50% within the first six months.

Combination therapies, such as using GP IIb/IIIa-antagonists with aspirin and a reduced dose of heparin, significantly enhance clinical outcomes while minimizing bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current aspects of thrombolytic therapy in unstable angina pectoris]. Voss, R., Tillmanns, H.[2019]

Calcium channel blockers, specifically third-generation dihydropyridine types, are safe for use in patients with heart failure, despite not significantly reducing mortality rates.

Standard heart failure therapy primarily includes angiotensin-converting enzyme inhibitors and beta-blockers, with calcium channel blockers not showing a specific role in improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for calcium channel blockers in congestive heart failure? Miller, AB.[2019]

The 2021 European Society of Cardiology guidelines emphasize the importance of early treatment with all four key drug classes for heart failure with reduced ejection fraction (HFrEF), which include ACE inhibitors, ARNI, beta-blockers, MRAs, and SGLT2 inhibitors.

This article serves as a practical guide for physicians to ensure safe and effective management of HFrEF, highlighting the need for comprehensive treatment strategies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. Soltani, S., Böhm, M., Frey, N., et al.[2022]

Early hospitalization and treatment are crucial for patients with acute coronary syndrome, involving a combination of medications like oxygen, analgesics, nitrates, beta blockers, and anticoagulants to stabilize their condition.

If initial treatments do not stabilize the patient, advanced therapies such as glycoprotein-IIb/IIIa receptor antagonists and coronary angiography may be necessary to manage severe cases effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current therapeutic strategies in acute coronary syndrome. New and established drug and interventional therapy]. Roth, M.[2010]

Heart failure with reduced ejection fraction (HFrEF) remains a serious condition with high mortality and hospitalization rates, highlighting the urgent need for effective pharmacological treatments.

Recent innovations in drug therapies for HFrEF are changing the treatment landscape, with ongoing studies focusing on both newly approved medications and experimental approaches to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovations in medical therapy of heart failure with reduced ejection fraction. Mercurio, V., Ambrosio, G., Correale, M., et al.[2023]

Newer slow-release and long-acting calcium antagonists, like nisoldipine and amlodipine, show promise in improving heart function and reducing mortality in patients with ventricular dysfunction, especially after acute myocardial infarction.

While some calcium antagonists have been associated with worsening heart failure, amlodipine demonstrated a significant 45% decrease in mortality in non-ischemic heart failure patients, although the exact mechanism for this benefit remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium antagonists in patients with left ventricular dysfunction: back on the bridge? Lewis, BS.[2019]

The polypill, which combines acetylsalicylic acid, ramipril, and either simvastatin or atorvastatin, has been shown to improve medication adherence in patients with ischemic heart disease, potentially leading to better control of cardiovascular risk factors.

In a clinical trial (FOCUS study), patients taking the polypill demonstrated higher adherence rates compared to those on separate medications, which may contribute to reduced blood pressure and LDL cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving cardiovascular protection: focus on a cardiovascular polypill. Barrios, V., Escobar, C.[2018]

In a study of 110 patients with heart failure and reduced ejection fraction (HFrEF), the inclusion of clinical pharmacists in the healthcare team significantly increased the percentage of patients reaching target doses of key medications, such as ACE inhibitors and beta blockers, from 0% to 77.4% and from 8.6% to 66.1%, respectively.

The up-titration of these medications led to notable improvements in clinical outcomes, including better ejection fraction and enhanced scores on the New York Heart Association (NYHA) scale, demonstrating the effectiveness of pharmacist interventions in managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacist's Intervention to Improve Medication Titration for Heart Failure: First Experience from Sudan. Ahmed, KO., Taj Eldin, I., Yousif, M., et al.[2022]

From 2013 to 2019, there was only a slight increase in the use of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), with β-blocker use rising from 64.2% to 72.0%, indicating a need for improved adherence to treatment guidelines.

Despite minimal changes in therapy rates, risk-adjusted mortality among patients with recent-onset HFrEF decreased from 19.9% to 18.4% over the same period, suggesting that while treatment uptake is low, there may still be improvements in patient outcomes that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Quality of Care for US Veterans With Recent-Onset Heart Failure With Reduced Ejection Fraction. Sandhu, AT., Kohsaka, S., Turakhia, MP., et al.[2022]

Beta-blockers, antialdosterone agents, and combined ARB/neprilysin inhibitors are effective in preventing sudden cardiac death (SCD) and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), based on a review of 41 systematic reviews.

Angiotensin-converting enzyme inhibitors (ACE-i) significantly reduce all-cause mortality but do not prevent SCD, indicating that alternative strategies may be needed for patients at high risk of SCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of drug interventions to prevent sudden cardiac death in patients with heart failure and reduced ejection fraction: an overview of systematic reviews. Al-Gobari, M., Al-Aqeel, S., Gueyffier, F., et al.[2021]

Polypills, which combine multiple generic drugs to target various cardiovascular risk factors, have shown consistent benefits in reducing both risk factors and major cardiovascular events based on data from randomized controlled trials.

Despite their effectiveness, polypills are not widely available, particularly in Europe, and there is a need for regulatory agencies to simplify the approval process to increase the number of polypills on the market, allowing more patients to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[When will we treat patients with a polypill shortly after myocardial infarction?] Lafeber, M., Peeters, L., Versmissen, J.[2023]

A qualitative study involving 17 patients revealed that many were skeptical about prescribing a polypill for cardiovascular disease prevention based solely on age, fearing unnecessary side effects despite acknowledging its potential benefits.

Patients were more open to the idea of a polypill for high-risk individuals or secondary prevention, but emphasized the need for ongoing monitoring of blood pressure and cholesterol levels, highlighting the importance of patient education in any broad implementation strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' views about taking a polypill to manage cardiovascular risk: a qualitative study in primary care. Virdee, SK., Greenfield, SM., Fletcher, K., et al.[2022]

Polypill therapy significantly reduced the risk of major adverse cardiac and cerebrovascular events (MACCE) in a study of 25,389 patients, showing a risk ratio of 0.78, indicating a 22% lower risk compared to control groups.

The polypill was also associated with improved adherence to treatment and did not increase the incidence of serious adverse events, making it a safe and effective option for both primary and secondary cardiovascular disease prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis on the Clinical Outcomes With Polypills for Cardiovascular Disease Prevention. Sedhom, R., Hamed, M., Tan, W., et al.[2023]

Polypills, which combine multiple medications to target various cardiovascular risk factors, could improve adherence to treatment and reduce the overall burden of taking multiple pills for patients at high cardiovascular risk.

The review highlights the need for discussions with regulatory bodies to ensure that the benefits of polypills are recognized, balancing safety concerns with the potential for significant public health improvements in managing cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits, challenges, and registerability of the polypill. Sleight, P., Pouleur, H., Zannad, F.[2013]

Many drug trials aimed at preventing restenosis have shown little to no clear benefit, particularly for antiplatelet and antithrombotic medications, indicating a need for more effective treatments.

While no single drug has proven conclusively effective, some antiproliferative agents and other drug classes show promise, suggesting that a combination of pharmacological and non-pharmacological strategies may help reduce restenosis rates in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological approaches for the prevention of restenosis after percutaneous coronary intervention. Lefkovits, J., Topol, EJ.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07032389

NCT07032389 | A Polypill for Acute Coronary Syndrome Given the significant pill burden for post-ACS patients, a polypill approach for patients in the subacute period following PCI may have substantial advantages.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12183251/

Efficacy of different polypill combinations for primary and ... Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J. (2008) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12466114/

The Polypill (Acetyl Salicylic Acid, Atorvastatin, and ... They (84.2%) also suggested that a polypill-based treatment might enhance coronary heart disease (CHD) outcomes at an equal or lower cost, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05514938

NCT05514938 | Polypill in Acute Coronary Syndrome Roughly 1/3 of ischemic heart disease is related to dyslipidemia, and statins are the mainstay of treatment. However, roughly 25-50% of patients discontinue ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2208275

Polypill Strategy in Secondary Cardiovascular Prevention The problem of adherence to therapy in patients with coronary heart disease ... outcomes, Heart Failure Reviews, (2025).https://doi.org/10.1007 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11950958/

rationale and protocol for the COMBO-HF-X pilot crossover ... Delivering guideline-directed medical therapy for heart failure with reduced ejection fraction as an over-encapsulated polypill.

7. ahajournals.org ahajournals.org/doi/10.1161/CIRCOUTCOMES.124.011121

Stakeholder Perspectives on a Heart Failure With Reduced ... ... heart failure with reduced ejection fraction (HFrEF) lead to worse patient outcomes. ... cardiovascular disease despite robust clinical trial ...

8. link.springer.com link.springer.com/article/10.1007/s10741-025-10559-2

Polypill in heart failure: a pathway to simplified treatment ... Polypill in heart failure: a pathway to simplified treatment and improved adherence and outcomes ... acute and chronic heart failure. Eur ...