Statin InTensity to Prevent Coronary Artery Vasculopathy After Heart Transplantation (SToP-CAV)

Statin InTensity to Prevent Coronary Artery Vasculopathy After Heart Transplantation - SToP-CAV

The investigator's propose to conduct an open-label randomized controlled trial to determine if higher intensity statin (HS) can reduce CAV in comparison to lower intensity statin (LS) after HT. All consecutive patients that meet eligibility criteria will be approached for participation. After heart transplantation, participants (n=70) will be randomized in a 1:1 manner to either HS or LS. Study participation will be for 2 years from the time of randomization. Study outcomes will be compared by research staff blinded to statin group assignment.

Study Overview

• Status: Withdrawn
• Conditions: Vasculopathy
• Intervention / Treatment: Drug: Atorvastatin 80 Mg Oral Tablet; Drug: Pravastatin 40 Mg Oral Tablet

Detailed Description

Outcomes after heart transplantation (HT) are limited by development of coronary allograft vasculopathy (CAV). CAV comprises of macro- and microvascular coronary disease and is the third leading cause of graft dysfunction and late mortality following HT. The pathophysiology of CAV is multifactorial and major pathways that are implicated include inflammation and dyslipidemia. These pathways are inhibited by statins which serve as the mainstay of CAV prevention.

The International Society of Heart and Lung Transplantation (ISHLT) guidelines recommend administration of low intensity statins (LS) due to a potential drug-drug interaction (DDI) with calcineurin inhibition (CNI) therapy. This DDI is related to concurrent use of an older generation CNI, cyclosporin A (CsA). CsA inhibits intestinal P-glycoprotein to reduce the efflux of statin into the gastrointestinal tract, thereby increasing statin levels in the blood and risk of myopathy. However, the current generation of CNI being utilized in most patients, Tacrolimus, does not inhibit P glycoprotein and may not impact statin levels after HT.

Despite use of LS, the residual risk of CAV development is elevated with nearly half of the patients having angiographic detection 5 years after HT. However, angiography is limited by its inability to detect microvascular disease and invasiveness. Early CAV is also detectable by non-invasive imaging with cardiac positron emission tomography (cPET) through measurement of myocardial flow reserve (MFR). MFR assesses total burden of macro- and microvascular disease and is well correlated with invasive measures of CAV and prognosis.

The protective and inhibitory effects of statins are proportional to their intensity with higher intensity statins (HS) leading to a greater reduction in low density lipoprotein (LDL) and inflammatory markers such as C-reactive protein (CRP) in comparison to LS. Despite these potentially beneficial effects of HS, LS remains the agent of choice for primary prevention of CAV after HT in the absence of a randomized controlled trial (RCT).

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Waitlisted for Heart Transplantation
• Capacity to provide informed consent

Exclusion Criteria:

• History of statin allergy or intolerance
• Hepatic dysfunction
• Redo Heart Transplant
• Awaiting combined heart and liver transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Higher Intensity Statin; Atorvastatin 80 milligram (mg) oral tablet	Drug: Atorvastatin 80 Mg Oral Tablet; Higher intensity statin; Other Names: Lipitor
Active Comparator: Lower Intensity Statin; Pravastatin 40 mg oral tablet	Drug: Pravastatin 40 Mg Oral Tablet; Lower intensity statin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Flow Reserve	Myocardial Flow Reserve measured by cardiac positron emission tomography	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Vascular Resistance	Coronary Vascular Resistance measured by cardiac positron emission tomography	2 year
Change in Global Longitudinal Strain	Change in Global Longitudinal Strain measured by echocardiography	baseline, 1 year and 2 year
Blood level of Low Density Lipoprotein	Blood level of Low Density Lipoprotein	baseline, 6, 12, 18, 24 months
Blood level of High Sensitivity C-Reactive Protein	Blood level of High Sensitivity C-Reactive Protein	baseline, 6, 12, 18, 24 months

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Omar Saeed, MD, MS, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: December 17, 2021
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (Actual): February 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Pravastatin
• Other Study ID Numbers: 2021-13700

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No