Safety and Effectiveness of PCSK9 Inhibitors in Orthotopic Heart Transplant Patients

Background Statin medications are recommended in patients after heart transplantation, but are sometimes poorly tolerated in the setting of concomitant use of calcineurin inhibitors. Alternative agents are often considered including PCSK9 inhibitors (PCSK9i). We sought to investigate the effects of PCSK9i use after heart transplant. Methods We identified patients transplanted from 1999 to 2019 who were prescribed a PCSK9i at our institution after transplant. We compared lipid profiles at baseline and at least 4 weeks after starting PCSK9i. Results from coronary angiography with intravascular ultrasound (IVUS) were also compared in a subset of patients who had studies before and after starting PCSK9i. Results We identified 68 patients in this analysis with a median age of 61.9 (51.2 - 67.4) years and 78% male. The median time from transplant to starting PCSK9i was 5.5 (2.7 - 10) years, while the median time on PCSK9i was 1.4 (0.6 - 2.7) years with 78% still on treatment. Evolocumab was used in 74%, Alirocumab was used in 13%, and both agents were used in 13% of patients (all due to insurance preference). The most common reason for initiation was elevated LDL cholesterol with statin intolerance (45 of 68). 17 patients were on a high intensity statin, and 5 patients could only tolerate lower intensity statins. There were 29% of patients on Ezetimibe. Median LDL decreased from 125 (101 - 148) mg/dl to 53 (37 - 72) mg/dl after starting PCSK9i (p < 0.001), with over 70% of patients achieving LDL <70 mg/dl after treatment. There were also significant reductions of total cholesterol, HDL, non-HDL cholesterol, and triglycerides at follow-up compared to baseline (Figure). 6 patients stopped PCSK9i permanently due to cost, and 4 patients stopped due to perceived side effects including elevated creatine kinase, myalgia, arthralgia, headache, shortness of breath, and abdominal pain. Serial coronary angiography with IVUS was performed in 19 patients: intimal thickness did not significantly progress in these patients compared to prior values [median time on PCSK9i 1.4 years; median change 0.005 (-0.09 to 0.095) mm; p = 0.33]. Among 8 patients with a second follow-up IVUS study, the lack of IVUS progression of vasculopathy was durable [median time on PCSK9i 2.7 years; median change 0.05 (-0.08 to 0.21) mm; p = 0.42]. Conclusions Among heart transplant recipients, PCSK9i are effective in lowering LDL levels and stabilizing coronary intimal hyperplasia with minimal side effects. Further evaluation of PCSK9i impact on post-heart transplant outcomes is warranted. Statin medications are recommended in patients after heart transplantation, but are sometimes poorly tolerated in the setting of concomitant use of calcineurin inhibitors. Alternative agents are often considered including PCSK9 inhibitors (PCSK9i). We sought to investigate the effects of PCSK9i use after heart transplant. We identified patients transplanted from 1999 to 2019 who were prescribed a PCSK9i at our institution after transplant. We compared lipid profiles at baseline and at least 4 weeks after starting PCSK9i. Results from coronary angiography with intravascular ultrasound (IVUS) were also compared in a subset of patients who had studies before and after starting PCSK9i. We identified 68 patients in this analysis with a median age of 61.9 (51.2 - 67.4) years and 78% male. The median time from transplant to starting PCSK9i was 5.5 (2.7 - 10) years, while the median time on PCSK9i was 1.4 (0.6 - 2.7) years with 78% still on treatment. Evolocumab was used in 74%, Alirocumab was used in 13%, and both agents were used in 13% of patients (all due to insurance preference). The most common reason for initiation was elevated LDL cholesterol with statin intolerance (45 of 68). 17 patients were on a high intensity statin, and 5 patients could only tolerate lower intensity statins. There were 29% of patients on Ezetimibe. Median LDL decreased from 125 (101 - 148) mg/dl to 53 (37 - 72) mg/dl after starting PCSK9i (p < 0.001), with over 70% of patients achieving LDL <70 mg/dl after treatment. There were also significant reductions of total cholesterol, HDL, non-HDL cholesterol, and triglycerides at follow-up compared to baseline (Figure). 6 patients stopped PCSK9i permanently due to cost, and 4 patients stopped due to perceived side effects including elevated creatine kinase, myalgia, arthralgia, headache, shortness of breath, and abdominal pain. Serial coronary angiography with IVUS was performed in 19 patients: intimal thickness did not significantly progress in these patients compared to prior values [median time on PCSK9i 1.4 years; median change 0.005 (-0.09 to 0.095) mm; p = 0.33]. Among 8 patients with a second follow-up IVUS study, the lack of IVUS progression of vasculopathy was durable [median time on PCSK9i 2.7 years; median change 0.05 (-0.08 to 0.21) mm; p = 0.42]. Among heart transplant recipients, PCSK9i are effective in lowering LDL levels and stabilizing coronary intimal hyperplasia with minimal side effects. Further evaluation of PCSK9i impact on post-heart transplant outcomes is warranted.