Impact of Statin Use After Heart Transplantation

Abstract

Background— Although various studies revealed the beneficial effects of statins in post–cardiac transplant patients, these were relatively small and low-powered studies. We performed a meta-analysis of published studies to evaluate the role of statins in post–cardiac transplant patients, specifically examining the effects on hemodynamically significant/fatal graft rejection, coronary vasculopathy, terminal cancer, and overall survival. Methods and Results— We searched PubMed, Cochran CENTRAL, and Web of Science databases using the search terms “cardiac transplant” or “heart transplant,” and “statin” for a literature search. A random-effects model with Mantel–Haenszel method was used to pool the data. We identified 10 studies, 4 randomized controlled trials, and 6 nonrandomized studies, which compared outcomes in heart transplant recipients undergoing statin therapy to statin-naive patients. A pooled analysis of 9 studies reporting mortality revealed that the use of statins was associated with significant reduction in all-cause mortality (odds ratio, 0.26; 95% confidence interval, 0.20–0.35; P <0.0001). Statins also decreased the odds of hemodynamically significant/fatal rejection (odds ratio, 0.37; 95% confidence interval, 0.21–0.65; P =0.0005), incidence of coronary vasculopathy (odds ratio, 0.33; 95% confidence interval, 0.16–0.68; P =0.003), and terminal cancer (odds ratio, 0.30; 95% confidence interval, 0.15–0.63; P =0.002). Conclusions— The evidence from a pooled analysis suggests that statins improve survival in heart transplant recipients. Statins may prevent fatal rejection episodes, decrease terminal cancer risk, and reduce the incidence of coronary vasculopathy. Additional prospective studies are needed to further investigate and explain this association.

Cardiac allograft vasculopathy: Insights on pathogenesis and therapy

“…Routine use of statins is recommended for all HT recipients. In addition to lowering serum cholesterol, statins have been shown to lower the incidence of CAV, reduce hemodynamically significant rejection episodes and improve survival . The major randomized controlled trials on statins post‐HT are summarized inTable .…”

“…Statins inhibit 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) and have pleiotropic properties that are independent of its lipid‐lowering effects . These immunomodulatory effects include suppression of natural killer cell cytotoxicity and improvement in coronary endothelial function . The timing of statin therapy is important with early initiation in the immediate postoperative period resulting in less development of CAV …”

“…In addition to lowering serum cholesterol, statins have been shown to lower the incidence of CAV, reduce hemodynamically significant rejection episodes and improve survival. 37 The major randomized controlled trials on statins post-HT are summarized inTable 4. [38][39][40][41][42][43] Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)…”

“…44 These immunomodulatory effects include suppression of natural killer cell cytotoxicity and improvement in coronary endothelial function. 37,45 The timing of statin therapy is important with early initiation in the immediate postoperative period resulting in less development of CAV. 43…”

New developments for the detection and treatment of cardiac vasculopathy

“…8 Subsequent studies have found similar benefits with other statins 74–77 and a meta-analysis of nine studies found statins decreased the odds of death by 76%, CAV by 67%, hemodynamically significant/fatal rejection by 63%, and terminal cancer by 70%. 78 …”