Skip to main content
Erschienen in: Herz 4/2019

07.11.2017 | Original articles

Effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events

A meta-analysis of randomized controlled trials

verfasst von: Y. Zhu, MD, X. Shen, MD, Q. Jiang, MB, Z. Wang, MD, Z. Wang, MM, X. Dong, MM, J. Li, MM, Q. Han, MM, J. Zhao, MM, B. Wang, MM, L. Liu, MM

Erschienen in: Herz | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

The present meta-analysis was designed to improve statistical power and review the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events.

Methods

PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to May 2017. Studies considered to be eligible were randomized controlled trials about the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events. The primary endpoint was positively adjudicated cardiovascular events; the secondary endpoint comprised cardiac mortality, myocardial infarction (MI), coronary revascularization, stroke, and hospitalization for unstable angina.

Results

We included 20 randomized controlled trials involving 67,934 patients. Monoclonal antibodies against PCSK9 were associated with a significant reduction in positively adjudicated cardiovascular events (relative risk [RR] = 0.87; 95% confidence interval [CI] = 0.81–0.93; z = 4.03; p = 0.000), MI (RR = 0.78; 95% CI = 0.71–0.86; z = 4.96; p = 0.000), coronary revascularization (RR = 0.81, 95% CI = 0.75–0.88; z = 4.93; p = 0.000), and stroke (RR = 0.76, 95% CI = 0.65–0.89; z = 3.47; p = 0.001). Monoclonal antibodies against PCSK9 did not reduce hospitalization rates due to unstable angina. The results of subgroup analysis showed that evolocumab was associated with a lower risk of positively adjudicated cardiovascular events, MI, coronary revascularization, and stroke without reducing cardiac mortality. Alirocumab reduced the incidence of cardiac mortality but not of other cardiovascular events, while bococizumab was associated with a reduced risk of stroke.

Conclusion

Monoclonal antibodies against PCSK9 were associated with a lower risk of positively adjudicated cardiovascular events, MI, coronary revascularization, and stroke.
Literatur
1.
Zurück zum Zitat Baigent C, Blackwell L, Emberson J, Cholesterol Treatment Trialists’(CTT) Collaboration (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: ameta-analysis of data from170,000 participants in 26 randomised trials. Lancet 376(9753):1670–1681CrossRef Baigent C, Blackwell L, Emberson J, Cholesterol Treatment Trialists’(CTT) Collaboration (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: ameta-analysis of data from170,000 participants in 26 randomised trials. Lancet 376(9753):1670–1681CrossRef
2.
Zurück zum Zitat McKenney JM, Koren MJ, Kereiakes DJ et al (2012) Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol 59(25):2344–2353CrossRef McKenney JM, Koren MJ, Kereiakes DJ et al (2012) Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol 59(25):2344–2353CrossRef
3.
Zurück zum Zitat Roth EM, McKenney JM, Hanotin C et al (2012) Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med 367(20):1891–1900CrossRef Roth EM, McKenney JM, Hanotin C et al (2012) Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med 367(20):1891–1900CrossRef
4.
Zurück zum Zitat Stein EA, Gipe D, Bergeron J et al (2012) Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet 380(9836):29–36CrossRef Stein EA, Gipe D, Bergeron J et al (2012) Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet 380(9836):29–36CrossRef
5.
Zurück zum Zitat Blom DJ, Hala T, Bolognese M et al (2014) 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 370(19):1809–1819CrossRef Blom DJ, Hala T, Bolognese M et al (2014) 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 370(19):1809–1819CrossRef
6.
Zurück zum Zitat Koren MJ, Lundqvist P, Bolognese M et al (2014) Anti-PCSK9 monotherapy for hypercholesterolemia:the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 63(23):2531–2540CrossRef Koren MJ, Lundqvist P, Bolognese M et al (2014) Anti-PCSK9 monotherapy for hypercholesterolemia:the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 63(23):2531–2540CrossRef
7.
Zurück zum Zitat Stroes E, Colquhoun D, Sullivan D et al (2014) Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance:the GAUSS-2 randomized, placebocontrolled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 63(23):2541–2548CrossRef Stroes E, Colquhoun D, Sullivan D et al (2014) Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance:the GAUSS-2 randomized, placebocontrolled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 63(23):2541–2548CrossRef
8.
Zurück zum Zitat Sabatine MS, Giugliano RP, Wiviott SD et al (2015) Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1500–1509CrossRef Sabatine MS, Giugliano RP, Wiviott SD et al (2015) Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1500–1509CrossRef
9.
Zurück zum Zitat Robinson JG, Farnier M, Krempf M et al (2015) Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1489–1499CrossRef Robinson JG, Farnier M, Krempf M et al (2015) Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1489–1499CrossRef
11.
Zurück zum Zitat Nissen SE, Stroes E, Dent-Acosta RE et al (2016) Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA 315(15):1580–1590CrossRef Nissen SE, Stroes E, Dent-Acosta RE et al (2016) Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA 315(15):1580–1590CrossRef
12.
Zurück zum Zitat Nicholls SJ, Puri R, Anderson T et al (2016) Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA 316(22):2373–2384CrossRef Nicholls SJ, Puri R, Anderson T et al (2016) Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA 316(22):2373–2384CrossRef
13.
Zurück zum Zitat Sabatine MS, Giugliano RP, Keech AC et al (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 376(18):1713–1722CrossRef Sabatine MS, Giugliano RP, Keech AC et al (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 376(18):1713–1722CrossRef
14.
Zurück zum Zitat Giugliano RP, Desai NR, Kohli P et al (2012) Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 380(9858):2007–2017CrossRef Giugliano RP, Desai NR, Kohli P et al (2012) Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 380(9858):2007–2017CrossRef
15.
Zurück zum Zitat Kiyosue A, Honarpour N, Kurtz C et al (2016) A phase 3 study of evolocumab (AMG 145) in statin-treated Japanese patients at high cardiovascular risk. Am J Cardiol 117(1):40–47CrossRef Kiyosue A, Honarpour N, Kurtz C et al (2016) A phase 3 study of evolocumab (AMG 145) in statin-treated Japanese patients at high cardiovascular risk. Am J Cardiol 117(1):40–47CrossRef
16.
Zurück zum Zitat Raal FJ, Stein EA, Dufour R et al (2015) PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 385(9965):331–340CrossRef Raal FJ, Stein EA, Dufour R et al (2015) PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 385(9965):331–340CrossRef
17.
Zurück zum Zitat Robinson JG, Nedergaard BS, Rogers WJ et al (2014) Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA 311(18):1870–1882CrossRef Robinson JG, Nedergaard BS, Rogers WJ et al (2014) Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA 311(18):1870–1882CrossRef
18.
Zurück zum Zitat Teramoto T, Kobayashi M, Tasaki H et al (2016) Efficacy and safety of alirocumab in Japanese patients with heterozygous familial hypercholesterolemia or at high cardiovascular risk with hypercholesterolemia not adequately controlled with statins – ODYSSEY JAPAN randomized controlled trial. Circ J 80(9):1980–1987CrossRef Teramoto T, Kobayashi M, Tasaki H et al (2016) Efficacy and safety of alirocumab in Japanese patients with heterozygous familial hypercholesterolemia or at high cardiovascular risk with hypercholesterolemia not adequately controlled with statins – ODYSSEY JAPAN randomized controlled trial. Circ J 80(9):1980–1987CrossRef
19.
Zurück zum Zitat Cannon CP, Cariou B, Blom D et al (2015) Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J 36(19):1186–1194CrossRef Cannon CP, Cariou B, Blom D et al (2015) Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J 36(19):1186–1194CrossRef
20.
Zurück zum Zitat Bays H, Gaudet D, Weiss R et al (2015) Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab 100(8):3140–3148CrossRef Bays H, Gaudet D, Weiss R et al (2015) Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab 100(8):3140–3148CrossRef
21.
Zurück zum Zitat Kastelein JJ, Robinson JG, Farnier M et al (2014) Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDL-C of 160 mg/dl or higher. Cardiovasc Drugs Ther 28(3):281–289CrossRef Kastelein JJ, Robinson JG, Farnier M et al (2014) Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDL-C of 160 mg/dl or higher. Cardiovasc Drugs Ther 28(3):281–289CrossRef
22.
Zurück zum Zitat Kastelein JJ, Ginsberg HN, Langslet G et al (2015) ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 36(43):2996–3003PubMedPubMedCentral Kastelein JJ, Ginsberg HN, Langslet G et al (2015) ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 36(43):2996–3003PubMedPubMedCentral
23.
Zurück zum Zitat Kereiakes DJ, Robinson JG, Cannon CP et al (2015) Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J 169(6):906–915CrossRef Kereiakes DJ, Robinson JG, Cannon CP et al (2015) Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J 169(6):906–915CrossRef
24.
Zurück zum Zitat Moriarty PM, Thompson PD, Cannon CP et al (2015) Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol 9(6):758–769CrossRef Moriarty PM, Thompson PD, Cannon CP et al (2015) Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol 9(6):758–769CrossRef
25.
Zurück zum Zitat Stroes E, Guyton JR, Lepor N et al (2016) Efficacy and safety of alirocumab 150 mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II study. J Am Heart Assoc 13;5(9:e3421 Stroes E, Guyton JR, Lepor N et al (2016) Efficacy and safety of alirocumab 150 mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II study. J Am Heart Assoc 13;5(9:e3421
26.
Zurück zum Zitat Ridker PM, Tardif JC, Amarenco P et al (2017) Lipid-reduction variability and antidrug-antibody formation with bococizumab. N Engl J Med 376(16):1517–1526CrossRef Ridker PM, Tardif JC, Amarenco P et al (2017) Lipid-reduction variability and antidrug-antibody formation with bococizumab. N Engl J Med 376(16):1517–1526CrossRef
27.
Zurück zum Zitat Ridker PM, Revkin J, Amarenco P et al (2017) Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med 376(16):1527–1539CrossRef Ridker PM, Revkin J, Amarenco P et al (2017) Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med 376(16):1527–1539CrossRef
28.
Zurück zum Zitat Ridker PM (2014) LDL cholesterol: controversies and future therapeutic directions. Lancet 384(9943):607–617CrossRef Ridker PM (2014) LDL cholesterol: controversies and future therapeutic directions. Lancet 384(9943):607–617CrossRef
29.
Zurück zum Zitat Preiss D, Seshasai SR, Welsh P et al (2011) Risk of incident diabetes with Intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305(24):2556–2564CrossRef Preiss D, Seshasai SR, Welsh P et al (2011) Risk of incident diabetes with Intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305(24):2556–2564CrossRef
Metadaten
Titel
Effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events
A meta-analysis of randomized controlled trials
verfasst von
Y. Zhu, MD
X. Shen, MD
Q. Jiang, MB
Z. Wang, MD
Z. Wang, MM
X. Dong, MM
J. Li, MM
Q. Han, MM
J. Zhao, MM
B. Wang, MM
L. Liu, MM
Publikationsdatum
07.11.2017
Verlag
Springer Medizin
Erschienen in
Herz / Ausgabe 4/2019
Print ISSN: 0340-9937
Elektronische ISSN: 1615-6692
DOI
https://doi.org/10.1007/s00059-017-4640-8

Weitere Artikel der Ausgabe 4/2019

Herz 4/2019 Zur Ausgabe

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.