Universal Time: 08:55  |  Local Time: 08:55 (0h GMT)
Select your timezone:
Room: E-Poster Hall

P-17.08 The evaluation of safety and efficacy of PCSK9 inhibitor in patients with cardiac allograft vasculopathy and hypercholesterolemia

Kensuke Kuroda, Japan

National Cerebral and Cardiovascular Center

Abstract

The evaluation of safety and efficacy of PCSK9 inhibitor in patients with cardiac allograft vasculopathy and hypercholesterolemia

Kensuke Kuroda1, Keiichiro Iwasaki1, Seiko Nakajima1, Takuya Watanabe1, Osamu Seguchi1, Masanobu Yanase1, Satsuki Fukushima2, Tomoyuki Fujita2, Junjiro Kobayashi2, Norihide Fukushima1.

1Transplant medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; 2Cardiovascular surgery, National Cerebral and Cardiovascular Center, Osaka, Japan

Background: Heart transplantation (HTX) has been performed from more elderly donors and donors with coronary arterial disease because of chronic donor shortage in Japan than other developed counties. Although the survival rate of HTX are relatively better and normal coronary arterial disease is less in Japan than other countries, cardiac allograft vasculopathy (CAV) has been remaining an important issue. Everolimus is administered aggressively for patients with CAV, but which sometimes causes difficulty to manage dyslipidemia.
Recently, protein convertase subtilisin/kexin 9 inhibitor (PCSK9i) has become available in Japan for patients with dyslipidemia. The purpose of this study is to investigate the efficacy and safety of PCSK9i in cardiac recipients with CAV.
Method: Consecutive patients that underwent HTX between 1999 and 2018 were assessed. Since 2018, evolocumab was administered at 420 mg monthly for patients with refractory high low-density lipoprotein (LDL) cholesterol levels (>100 mg/dL) or high LDL cholesterol with statin-induced high serum creatin kinase (CK). We investigated prospectively lipid changes, progression of CAV, and side effects after evolocumab administration.
Results: 113 adult patients underwent HTX during the study periods, of whom six patients were treated with evolocumab. The median age was 53.5 years (5 males) and the median follow-up period was 11.8 months. Primary cardiac disease was 3 of dilated cardiomyopathy, 1 of ischemic cardiomyopathy, and 2 of cardiomyopathy secondary to muscular dystrophy (MD). Everolimus was used in 5 out of 6 patients to prevent progression of CAV or renal dysfunction. At 6 months, the levels of total cholesterol, triglyceride, LDL cholesterol, high-density lipoprotein cholesterol, mature PCSK9, as compared with the baseline levels, were 203 vs 116 mg/dL (p = 0.001), 184 vs 134 mg/dL (p = 0.331), 115 vs 34 mg/dL (p = 0.001), 56 vs 58 mg/dL (p = 0.171), 328 vs 2811 ng/mL (p <0.001), respectively. In 4 patients who could follow intravascular ultrasound, maximal intimal thickness (MIT) of right and left coronary artery were 0.93 vs 0.90 mm (p = 0.718), 1.13 vs 0.90 (p = 0.459), respectively. A patient with MD stopped evolocumab because of myalgia, but no further increase of CK was observed. There were no side effects in other patients.
Discussion: PCSK9i lowered LDL cholesterol levels in cardiac recipients who were resistant to conventional therapy. Although CAV found no significant change in this study, PCSK9i might improve CAV because some of the individual cases reduced MIT. Moreover, mTOR inhibitors have also been reported to increase not only serum cholesterol but also serum PCSK9. PCSK9i might be more effective in cardiac recipients using everolimus which is one of the mTOR inhibitors.
Conclusion: PCSK9i was able to safely lower LDL cholesterol without any severe adverse effects in cardiac recipients.

Comments

There are no comments yet...

WebApp Sponsor

© 2024 TTS 2020