Abstract 11609: Neurological Effects of Proprotein Convertase Subtilisin/kexin Type 9(PCSK9) Inhibitors: Direct and Indirect Comparisons

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors dramatically reduce low-density lipoprotein (LDL) cholesterol levels which may lead to lower cerebrovascular (CVA) events. However, randomized control trials (RCTs) have reported increased neurocognitive (NC) deficits in patients using PCSK9 inhibitors. Hypothesis: CVA and NC event rates are similar in patients treated with or without PCSK9 inhibitors. Methods: RCTs reporting rates of stroke, transient ischemic attacks (TIAs), and NC deficits in patients using PCSK9 inhibitors were identified. Standard meta-analyses techniques were used to compare these outcomes among patients treated with and without PCSK9 inhibitors. Network meta-analyses (NMA) were also conducted to indirectly compare Evolocumab and Alirocumab on aforementioned outcomes. Results: Seventeen RCTs with 14,516 patients were included. Evolocumab was used in 10 RCTS in 6,403 patients whereas Alirocumab was used in 2,932 patients in 7 RCTs. Ten RCTs with 10,318 patients reported stroke. Fourteen RCTs with 12,578 patients reported NC event rates. Five RCTs with 6,710 patients reported TIAs ( Table ). None of the studies using Alirocumab reported data on TIAs. We did not observe any difference in stroke rate, NC deficits or TIAs among 2 studied groups (RR; 1.22, (95% CI: 0.50-2.96), 0.97 (0.43-2.20), and 0.37 (0.06-2.23)) respectively. We observed no difference in stroke and NC deficits among Evolocumab and Alirocumab with NMA ( Figure ). Conclusions: PCSK9 inhibitors did not render any protection from stroke or TIAs. Furthermore, our pooled analysis does not show any increase in NC deficits as reported in previous studies.