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

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Acute coronary syndromes (ACS) represent a major contributor to mortality, morbidity, and healthcare costs. Effective therapies are widely available; however, adherence is low. This contributes to worse patient outcomes and increased risk of morbidity and mortality. The once-daily polypill leverages a population-based strategy that has previously demonstrated efficacy in improving adherence and access to therapy in low-resource settings, making it an innovative approach for improving post-ACS care. This study aims to investigate the utility of a polypill-based strategy for patients with ACS with drug eluting stent (DES) placement. The polypill will consist of a high-intensity statin (rosuvastatin 40 mg daily), aspirin 81 mg daily, and either clopidogrel 75 mg or prasugrel 10 mg daily.

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.

What data supports the effectiveness of the Polypill drug for Acute Coronary Syndrome?

The research highlights that medications improving outcomes in heart failure with reduced ejection fraction (HFrEF) are often underused, and the involvement of clinical pharmacists can optimize these treatments. This suggests that a comprehensive approach, like the Polypill, which combines multiple medications, could be effective in managing complex heart conditions by ensuring patients receive all necessary drugs at appropriate doses. ^{1 2 3 4 5}

Is the polypill safe for humans?

Research shows that the polypill is generally safe for humans, as studies found no increase in serious adverse events compared to other treatments. It also helps improve medication adherence, which can lead to better health outcomes. ^{6 7 8 9 10}

What makes the Polypill drug unique for treating acute coronary syndrome?

The Polypill is unique because it combines multiple medications into a single pill, which can simplify treatment by reducing the number of pills a patient needs to take. This can improve adherence to the treatment plan, potentially leading to better outcomes for patients with acute coronary syndrome. ^{11 12 13 14 15}

Research Team

Ambarish Pandey, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Clinical Pharmacist's Intervention to Improve Medication Titration for Heart Failure: First Experience from Sudan. [2022]

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

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. [2022]

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

Innovations in medical therapy of heart failure with reduced ejection fraction. [2023]

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

Evaluation of Quality of Care for US Veterans With Recent-Onset Heart Failure With Reduced Ejection Fraction. [2022]

5. England 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. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

[When will we treat patients with a polypill shortly after myocardial infarction?] [2023]

7. England pubmed.ncbi.nlm.nih.gov

Patients' views about taking a polypill to manage cardiovascular risk: a qualitative study in primary care. [2022]

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

Improving cardiovascular protection: focus on a cardiovascular polypill. [2018]

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

Meta-Analysis on the Clinical Outcomes With Polypills for Cardiovascular Disease Prevention. [2023]

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

Benefits, challenges, and registerability of the polypill. [2013]

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

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

12. Germany pubmed.ncbi.nlm.nih.gov

[Current aspects of thrombolytic therapy in unstable angina pectoris]. [2019]

13. Germany pubmed.ncbi.nlm.nih.gov

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

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

Pharmacological approaches for the prevention of restenosis after percutaneous coronary intervention. [2021]

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

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