Simvastatin protects donor hearts against ischemic damage
A single dose of the lipid-lowerer simvastatin, delivered to an organ donor pre-heart transplant, could decrease postoperative troponin levels in transplant recipients and protect the donor heart against perioperative myocardial ischemic damage.
That’s according to a study authored by Antti I. Nykanen, MD, PhD, and colleagues and published this summer in Circulation. Nykanen and his team at the University of Helsinki and Helsinki University Hospital in Finland investigated the utility of simvastatin, a CV drug marketed under the brand name Zocor, in protecting donor hearts by inhibiting allograft ischemia-reperfusion injury.
The authors said the results of heart transplantation have improved greatly in recent years, but a handful of confounders still complicate recipients’ short- and long-term odds of survival. Events early on in the transplant process—like brain death that activates early immune responses and causes transplant ischemia-reperfusion injury—could be key determinants of procedural success.
“Current immunosuppressive drugs do not prevent ischemia-reperfusion injury or cardiac allograft vasculopathy,” Nykanen et al. wrote in their report. “Therefore, treatment strategies that limit early injury and immune activation may have beneficial effects, especially today, when older and marginal, nonoptimal donors are accepted for heart transplantation.”
The team randomized their 84 multiorgan donors to receive either 80 mg of simvastatin prior to transplantation or no simvastatin at all. In patients who did receive the drug, simvastatin was delivered via nasogastric tube after declaration of brain death and upon a person’s acceptance as a cardiac donor.
Nykanen and colleagues reported that treatment with simvastatin “significantly” reduced heart recipients’ plasma levels of both troponin T and troponin I—by 34% and 40% at six hours after reperfusion, respectively. Recipients’ levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) also fell 36% at one week, and the number of rejection treatments with hemodynamic compromise was reduced 53% within the first 30 days of surgery.
The authors said donor simvastatin treatment didn’t affect donor lipid levels, but it was linked to a decrease in recipient post-op plasma levels of CXCL10 (C-X-C motif chemokine 10), interleukin-1a, placental growth factor and platelet-derived growth factor-BB. Postoperative hemodynamics, biopsy-proven acute rejection and mortality were similar between groups, and no adverse effects were observed in transplant recipients who received noncardiac solid organ transplants from simvastatin-treated donors.
“The study provides important new information,” Josef Stehlik, MD, MPH, and Line Kemeyou, MD, wrote in a related editorial. “It extends findings that showed benefit of donor statin administration in an experimental model to clinical transplantation. These findings are far from definitive; however, the study provides safety and feasibility data for larger-scale testing of this intervention in the multiorgan donor.
“Importantly, the study results also raise the question of whether additional benefit could be derived from earlier use of statins in the transplant recipient, perhaps when initiated even before the transplant and continued in the immediate post-transplant period.”
Stehlik and Kemeyou did note some limitations in Nykanen et al.’s work, including the fact that there was significant imbalance in the baseline characteristics of donors in the two groups. Still, they said, the team should be lauded for “successfully conducting a RCT in the exceptionally challenging circumstances of multiorgan donation.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.