TY - JOUR
T1 - Association of baseline LDL-C with total and cardiovascular mortality in patients using proprotein convertase subtilisin-kexin type 9 inhibitors
T2 - A systematic review and meta-analysis
AU - Khan, Safi U.
AU - Riaz, Haris
AU - Rahman, Hammad
AU - Khan, Muhammad U.
AU - Khan, Muhammad Shahzeb
AU - Alkhouli, Mohamad
AU - Kaluski, Edo
AU - Leucker, Thorsten M.
AU - Blaha, Michael J.
N1 - Funding Information:
Authors' contributions: Khan S.U. contributed to the conception and design of the work, data acquisition, analysis, data interpretation, and writing the manuscript. Riaz H. and Rahman H. contributed in drafting the manuscript. Khan M.U. and Khan M.S. were involved in data acquisition and quality assessment. Alkhouli M. Kaluski E. Leucker T.M. and Blaha M.J. all critically reviewed the manuscript.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Background: The objective of this study was to investigate whether baseline low-density lipoprotein cholesterol (LDL-C) levels influence total and cardiovascular mortality reduction associated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy. Methods: In this meta-analysis, 9 randomized controlled trials were selected using Medline, Embase, and CENTRAL until November 2018. Analyses were stratified by mean baseline LDL-C (<100 mg/dL and ≥ 100 mg/dL). Stepwise prespecified sensitivity analyses were performed after excluding the SPIRE trials and by regrouping ODYSSEY OUTCOME mortality data according to the baseline LDL-C (< and ≥100 mg/dL). Results: In 83,321 patients, PCSK9 inhibitor therapy was not associated with a reduction in the risk of all-cause mortality (relative risk [RR], 0.94, 95% confidence interval [CI], 0.81–1.09, P =.41). These results remained consistent after excluding the SPIRE trials (RR, 0.89, 95% CI, 0.75–1.05, P =.18). However, the RR varied by baseline LDL-C, with significant RR reduction only in patients with LDL-C ≥ 100 mg/dL (RR, 0.39, 95% CI, 0.20–0.76) (P-interaction =.01). Meta-regression showed RR of 0.97 for all-cause mortality per 1 mg/dL higher baseline LDL-C (95% CI, 0.94–0.99). PCSK9 inhibitor therapy showed no significant effect on cardiovascular mortality, with no effect when excluding the SPIRE trials. However, after regrouping ODYSSEY OUTCOME estimates, there was a significant reduction in cardiovascular mortality restricted to patients with LDL-C ≥ 100 mg/dL (RR, 0.67, 95% CI, 0.51–0.87) (P-interaction =.006). Conclusion: PCSK9 inhibitor therapy on a background statin treatment may reduce the risk of total and cardiovascular mortality in patients with baseline LDL-C ≥ 100 mg/dL. These results support current guidelines reserving PCSK9 inhibitors for high-risk patients with residually high LDL-C.
AB - Background: The objective of this study was to investigate whether baseline low-density lipoprotein cholesterol (LDL-C) levels influence total and cardiovascular mortality reduction associated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy. Methods: In this meta-analysis, 9 randomized controlled trials were selected using Medline, Embase, and CENTRAL until November 2018. Analyses were stratified by mean baseline LDL-C (<100 mg/dL and ≥ 100 mg/dL). Stepwise prespecified sensitivity analyses were performed after excluding the SPIRE trials and by regrouping ODYSSEY OUTCOME mortality data according to the baseline LDL-C (< and ≥100 mg/dL). Results: In 83,321 patients, PCSK9 inhibitor therapy was not associated with a reduction in the risk of all-cause mortality (relative risk [RR], 0.94, 95% confidence interval [CI], 0.81–1.09, P =.41). These results remained consistent after excluding the SPIRE trials (RR, 0.89, 95% CI, 0.75–1.05, P =.18). However, the RR varied by baseline LDL-C, with significant RR reduction only in patients with LDL-C ≥ 100 mg/dL (RR, 0.39, 95% CI, 0.20–0.76) (P-interaction =.01). Meta-regression showed RR of 0.97 for all-cause mortality per 1 mg/dL higher baseline LDL-C (95% CI, 0.94–0.99). PCSK9 inhibitor therapy showed no significant effect on cardiovascular mortality, with no effect when excluding the SPIRE trials. However, after regrouping ODYSSEY OUTCOME estimates, there was a significant reduction in cardiovascular mortality restricted to patients with LDL-C ≥ 100 mg/dL (RR, 0.67, 95% CI, 0.51–0.87) (P-interaction =.006). Conclusion: PCSK9 inhibitor therapy on a background statin treatment may reduce the risk of total and cardiovascular mortality in patients with baseline LDL-C ≥ 100 mg/dL. These results support current guidelines reserving PCSK9 inhibitors for high-risk patients with residually high LDL-C.
KW - Meta-analysis
KW - Mortality
KW - Proprotein convertase subtilisin-kexin type 9 inhibitors
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U2 - 10.1016/j.jacl.2019.05.014
DO - 10.1016/j.jacl.2019.05.014
M3 - Review article
C2 - 31278046
AN - SCOPUS:85068228167
VL - 13
SP - 538
EP - 549
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
SN - 1933-2874
IS - 4
ER -