Ignite Creation Date:
2024-05-06 @ 6:00 PM
Last Modification Date:
2024-10-26 @ 2:40 PM
Study NCT ID:
NCT05514938
Status:
RECRUITING
Last Update Posted:
2024-05-30
First Post:
2022-08-22
Brief Title:
Polypill in Acute Coronary Syndrome
Sponsor:
University of Texas Southwestern Medical Center
Organization:
University of Texas Southwestern Medical Center
Study Overview
Official Title:
Polypill Strategy for Evidence-Based Management of Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention in an Underserved Patient Population
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
POLY-ACS
Brief Summary:
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
Detailed Description:
Acute coronary syndromes ACS represent a large contributor to patient morbidity and mortality and healthcare costs Patients with suspected ACS are referred for diagnostic coronary angiography and if obstructive coronary disease is found percutaneous coronary intervention PCI with a drug-eluding stent DES has been proven to reduce mortality and reduce recurrent myocardial infarction Medical therapy for ACS involves treatment with a statin and dual antiplatelet drug therapy with aspirin and P2Y12 inhibition
Dual antiplatelet therapy DAPT is a vital aspect of post-PCI care and ensures stent patency Aspirin blocks metabolism of arachidonic acid and production of thromboxane A2 through irreversible inhibition of cyclooxygenase 1 Prasugrel and clopidogrel are irreversible inhibitors of the platelet P2Y12 ADP receptors while ticagrelor is a reversible inhibitor of the platelet P2Y12 ADP receptor Current guidelines recommend dual antiplatelet therapy for at least 1 month and ideally up to 1 year for patients treated medically and at least 1 year for patients treated with DES after hospitalization for ACS
Additionally lipid lowering therapy is a cornerstone of post-ACS care Multiple studies have demonstrated a direct correlation between low-density lipoprotein cholesterol LDL-C levels and ASCVD risk Statins 3-hydroxy-3-methylgultaryl-coenzyme A reductase inhibitors are first-line therapies used to achieve LDL-C reductions High-intensity statins such as atorvastatin 40 mg or 80 mg or rosuvastatin 20 mg or 40 mg can lower LDL-C by 50 and patients with history of ACS have greater benefit from high-intensity statins versus low-intensity statins Importantly administration of a high-intensity statin is a Class 1 recommendation from the AHAACC Non-ST-Elevation ACS guidelines and the ST-Elevation ACS guidelines
The combination of prompt diagnosis of ACS management with coronary angiography with possible DES placement and medical therapy including DAPT has led to improvements in ACS mortality However nonadherence to cardiovascular medications is common Data from the US Veterans Affairs hospitals show that nearly 30 of patients did not refill clopidogrel after index hospitalization for ACS In a study of the PREMIER registry one in seven patients stopped taking clopidogrel therapy after 1 month and those who stopped had ninefold elevated risk of death within 1 year Poor adherence to antiplatelet therapy with either aspirin or P2Y12 inhibitors can lead to in-stent thrombosis a particularly morbid occurrence characterized by high patient morbidity and mortality Early stoppage of dual antiplatelet therapy increases risk of stent thrombosis 90-fold
Nonadherence to statins is also well documented Roughly 13 of ischemic heart disease is related to dyslipidemia and statins are the mainstay of treatment However roughly 25-50 of patients discontinue their statin therapy within the first year after treatment initiation Lipid reduction is a proven strategy to prevent further cardiovascular events however medication nonadherence is a significant barrier
The polypill is a potential strategy for increasing utilization of proven ACS therapies The polypill refers to a fixed-dose combination of once-daily medication with proven benefits The feasibility of a polypill-based strategy has been demonstrated for the primary prevention of cardiovascular events Among patients with hypertension at a federally qualified community health center the polypill led to a reduction in systolic blood pressure -7 mm Hg 95 CI -2 to -12 p0003 and low-density lipoprotein cholesterol -11 mgdl 95 CI -5 to -18 p00003 Multi-drug combinations have additionally been employed in the Indian Polycap Study HOPE-3 trial UMPIRE trial and most recently in the PolyIran study which demonstrated high rates of adherence and low rates of adverse events13-16 In PolyIran the largest of these studies more than 6500 healthy individuals were enrolled and randomized to treatment with a polypill containing low doses of a thiazide diuretic aspirin statin and ACEARB versus no pharmacologic intervention for primary prevention of cardiovascular disease Among those receiving the polypill a 34 risk reduction in major cardiovascular events was observed compared to standard treatment In the smaller UMPIRE trial moreover adherence among participants receiving a polypill formulation was more than three-fold higher than in those receiving usual care Few studies have enrolled disadvantaged US populations to date and no study to our knowledge has evaluated a polypill strategy for treatment of heart failure where pill burden and adherence continue to present obstacles to improving care
No randomized trial has evaluated a polypill strategy for the treatment of ACS Given the significant pill burden and challenges with adherence a polypill strategy may have substantial advantages Thus we have planned a single-center open-label pragmatic pilot study of a polypill-based strategy for the treatment of ACS The polypill will consist of a high-intensity statin rosuvastatin 40 mg daily aspirin 81 mg daily and clopidogrel 75 mg or prasugrel 10 mg daily The rationale for the trial is summarized as follows
Acute coronary syndromes 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
Dual antiplatelet therapy DAPT is a vital aspect of post-PCI care and ensures stent patency Aspirin blocks metabolism of arachidonic acid and production of thromboxane A2 through irreversible inhibition of cyclooxygenase 1 Prasugrel and clopidogrel are irreversible inhibitors of the platelet P2Y12 ADP receptors while ticagrelor is a reversible inhibitor of the platelet P2Y12 ADP receptor Current guidelines recommend dual antiplatelet therapy for at least 1 month and ideally up to 1 year for patients treated medically and at least 1 year for patients treated with DES after hospitalization for ACS
Additionally lipid lowering therapy is a cornerstone of post-ACS care Multiple studies have demonstrated a direct correlation between low-density lipoprotein cholesterol LDL-C levels and ASCVD risk Statins 3-hydroxy-3-methylgultaryl-coenzyme A reductase inhibitors are first-line therapies used to achieve LDL-C reductions High-intensity statins such as atorvastatin 40 mg or 80 mg or rosuvastatin 20 mg or 40 mg can lower LDL-C by 50 and patients with history of ACS have greater benefit from high-intensity statins versus low-intensity statins Importantly administration of a high-intensity statin is a Class 1 recommendation from the AHAACC Non-ST-Elevation ACS guidelines and the ST-Elevation ACS guidelines
The combination of prompt diagnosis of ACS management with coronary angiography with possible DES placement and medical therapy including DAPT has led to improvements in ACS mortality However nonadherence to cardiovascular medications is common Data from the US Veterans Affairs hospitals show that nearly 30 of patients did not refill clopidogrel after index hospitalization for ACS In a study of the PREMIER registry one in seven patients stopped taking clopidogrel therapy after 1 month and those who stopped had ninefold elevated risk of death within 1 year Poor adherence to antiplatelet therapy with either aspirin or P2Y12 inhibitors can lead to in-stent thrombosis a particularly morbid occurrence characterized by high patient morbidity and mortality Early stoppage of dual antiplatelet therapy increases risk of stent thrombosis 90-fold
Nonadherence to statins is also well documented Roughly 13 of ischemic heart disease is related to dyslipidemia and statins are the mainstay of treatment However roughly 25-50 of patients discontinue their statin therapy within the first year after treatment initiation Lipid reduction is a proven strategy to prevent further cardiovascular events however medication nonadherence is a significant barrier
The polypill is a potential strategy for increasing utilization of proven ACS therapies The polypill refers to a fixed-dose combination of once-daily medication with proven benefits The feasibility of a polypill-based strategy has been demonstrated for the primary prevention of cardiovascular events Among patients with hypertension at a federally qualified community health center the polypill led to a reduction in systolic blood pressure -7 mm Hg 95 CI -2 to -12 p0003 and low-density lipoprotein cholesterol -11 mgdl 95 CI -5 to -18 p00003 Multi-drug combinations have additionally been employed in the Indian Polycap Study HOPE-3 trial UMPIRE trial and most recently in the PolyIran study which demonstrated high rates of adherence and low rates of adverse events13-16 In PolyIran the largest of these studies more than 6500 healthy individuals were enrolled and randomized to treatment with a polypill containing low doses of a thiazide diuretic aspirin statin and ACEARB versus no pharmacologic intervention for primary prevention of cardiovascular disease Among those receiving the polypill a 34 risk reduction in major cardiovascular events was observed compared to standard treatment In the smaller UMPIRE trial moreover adherence among participants receiving a polypill formulation was more than three-fold higher than in those receiving usual care Few studies have enrolled disadvantaged US populations to date and no study to our knowledge has evaluated a polypill strategy for treatment of heart failure where pill burden and adherence continue to present obstacles to improving care
No randomized trial has evaluated a polypill strategy for the treatment of ACS Given the significant pill burden and challenges with adherence a polypill strategy may have substantial advantages Thus we have planned a single-center open-label pragmatic pilot study of a polypill-based strategy for the treatment of ACS The polypill will consist of a high-intensity statin rosuvastatin 40 mg daily aspirin 81 mg daily and clopidogrel 75 mg or prasugrel 10 mg daily The rationale for the trial is summarized as follows
Acute coronary syndromes 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None