Clinical trial NCT05251129: Statin InTensity to Prevent Coronary Artery Vasculopathy After Heart Transplantation
Official title: Statin InTensity to Prevent Coronary Artery Vasculopathy After Heart Transplantation - SToP-CAV
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Vasculopathy
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2022-02-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, randomized controlled trial
Primary purpose: PREVENTION

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Myocardial Flow Reserve
timeFrame: 2 year
Secondary outcomes:
measure: Coronary Vascular Resistance
timeFrame: 2 year
measure: Change in Global Longitudinal Strain
timeFrame: baseline, 1 year and 2 year
measure: Blood level of Low Density Lipoprotein
timeFrame: baseline, 6, 12, 18, 24 months
measure: Blood level of High Sensitivity C-Reactive Protein
timeFrame: baseline, 6, 12, 18, 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Montefiore Medical Center
name: Omar Saeed, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: