Article type
Year
Abstract
Background: Despite the availability of effective therapies for reducing low-density lipid-cholesterol (LDL-C), atherosclerotic cardiovascular disease (CVD) remains an important source of mortality and morbidity. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK-9) enzyme, using monoclonal antibodies (PCSK9 inhibitors) further LDL-C reduction may be achieved, potentially decreasing CVD risk as well.
Objectives: To quantify the short- (24 weeks), medium- (one year), and long-term (five year) effects of PCSK9 inhibitors on lipids, CVD risk, and safety.
Main results: We included 17 studies, with data on 13,341 subjects, which consisted primarily of older patients (median age 60.21 years) with a history of CVD (73%), and elevated LDL-C (median 125.83 mg/dL). PCSK9 inhibitors were associated with a decrease in LDL-C (-45.70% (95% CI -52.40 to -39.01)), Apolipoprotein B (-35.15% (95% CI -43.86 to -26.45)) and lipoprotein [a] (-18.50% (95% CI -22.88 to -14.12)), and with an increase in HDL-C (6.44% (95% CI 4.57 to 8.32)), and apolipoprotein A1 (4.55% (95% CI 3.04 to 6.06)). This effect was consistent over 6 months and 1-year follow-up.
PCSK9 inhibitors decreased all-cause mortality (OR 0.42 (95% CI 0.24 to 0.74)), which was potentially in part due to decreased odds of any CVD (OR 0.82 (95% CI 0.63 to 1.07)) or any MI (OR 0.73 (95% CI 0.45 to 1.21). Subjects randomized to PCSK9 inhibitors reported a higher incidence of any adverse event (OR 1.11 (95% CI 1.02 to 1.21)), partly due to an increase odds of influenza (OR 1.21 (95% CI 0.99 to 1.48)) or possibly myalgia (OR 1.10 (95% CI 0.90 to 1.35)).
The risk of bias assessment was low for biomarker endpoints. However, due to the inclusion of open label trials the risk of bias was perceived to be higher for clinical endpoints such as CVD or adverse events.
Authors' conclusions: Over short to medium follow-up PCSK9 inhibitors reduce LDL-C, apolipoprotein B, lipoprotein [a], and increased HDL-C and apolipoprotein A1. PCSK9 inhibitors seemed to reduced mortality risk, which was potentially related to a decrease in CVD risk; however, this needs additional confirmation in longer follow-up blinded RCTs.
Objectives: To quantify the short- (24 weeks), medium- (one year), and long-term (five year) effects of PCSK9 inhibitors on lipids, CVD risk, and safety.
Main results: We included 17 studies, with data on 13,341 subjects, which consisted primarily of older patients (median age 60.21 years) with a history of CVD (73%), and elevated LDL-C (median 125.83 mg/dL). PCSK9 inhibitors were associated with a decrease in LDL-C (-45.70% (95% CI -52.40 to -39.01)), Apolipoprotein B (-35.15% (95% CI -43.86 to -26.45)) and lipoprotein [a] (-18.50% (95% CI -22.88 to -14.12)), and with an increase in HDL-C (6.44% (95% CI 4.57 to 8.32)), and apolipoprotein A1 (4.55% (95% CI 3.04 to 6.06)). This effect was consistent over 6 months and 1-year follow-up.
PCSK9 inhibitors decreased all-cause mortality (OR 0.42 (95% CI 0.24 to 0.74)), which was potentially in part due to decreased odds of any CVD (OR 0.82 (95% CI 0.63 to 1.07)) or any MI (OR 0.73 (95% CI 0.45 to 1.21). Subjects randomized to PCSK9 inhibitors reported a higher incidence of any adverse event (OR 1.11 (95% CI 1.02 to 1.21)), partly due to an increase odds of influenza (OR 1.21 (95% CI 0.99 to 1.48)) or possibly myalgia (OR 1.10 (95% CI 0.90 to 1.35)).
The risk of bias assessment was low for biomarker endpoints. However, due to the inclusion of open label trials the risk of bias was perceived to be higher for clinical endpoints such as CVD or adverse events.
Authors' conclusions: Over short to medium follow-up PCSK9 inhibitors reduce LDL-C, apolipoprotein B, lipoprotein [a], and increased HDL-C and apolipoprotein A1. PCSK9 inhibitors seemed to reduced mortality risk, which was potentially related to a decrease in CVD risk; however, this needs additional confirmation in longer follow-up blinded RCTs.