Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials

Background: According to ACC/ AHA guidelines, a minimum of 1 year of dual anti- platelet therapy (DAPT) consisting of aspirin and a platelet ADP-receptor antagonist (P2Y12 inhibitor) is recommended for patients presenting acute coronary syndromes (ACS), regardless of which type of revascularization is performed during the acute event. Methods: The purpose of this presentation was to review the present data either from a direct randomized comparison among the three compounds and also large prospective observational registries and meta-analysis were analyzed in detail. With this aim, we performed an extensive large search from PubMed/Medline Journals identifying studies comparing fashion the new P2Y12 inhibitors in patients with ACS including ST elevation myocardial infarction (STEMI) in direct and indirect manner. Results: Pivotal large randomized clinical trials (RCT) in patients with ACS including STEMI, comparing clopidogrel, a first generation P2Y12 inhibitor against the newer prasugrel and ticagrelor showed major efficacy advantages of the latters although both drugs had more bleeding risk than clopidogrel. Direct comparisons of prasugrel and ticagrelor from large RCT are not yet available, however, several observational registries and metaanalysis reported results from an indirect comparison between both compounds. Major findings and limitations of each of these studies were identified, highlighted and discussed. Conclusion: Prasugrel and ticagrelor are both more effective than clopidogrel to prevent adverse cardiac events in patients with ACS. Compared to ticagrelor, prasugrel appears to be more effective in patients with STEMI, although lack of randomized data didn’t allow to draw definitive conclusions.

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Clinical Trials with Glycoprotein IIb/IIIa Receptor Antagonists in Acute Coronary Syndromes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657528 ◽

1997 ◽

Vol 78 (01) ◽

pp. 210-213 ◽

Cited By ~ 16

Author(s):

Frans Van de Werf

Keyword(s):

Clinical Trials ◽

Acute Coronary Syndromes ◽

Receptor Antagonists ◽

Coronary Syndromes

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Delayed versus Early Renal Replacement Therapy for Severe Acute Kidney Injury: A Systematic Review and Individual Patient Data Meta-Analysis of Randomised Clinical Trials

SSRN Electronic Journal ◽

10.2139/ssrn.3526302 ◽

2020 ◽

Author(s):

Stephane Gaudry ◽

David Hajage ◽

Nicolas Benichou ◽

Khalil Chaïbi ◽

Saber Barbar ◽

...

Keyword(s):

Systematic Review ◽

Acute Kidney Injury ◽

Clinical Trials ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Individual Patient Data ◽

Meta Analysis ◽

Kidney Injury ◽

Patient Data ◽

Randomised Clinical Trials

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Is there Sex-related Outcome Difference According to oral P2Y12 Inhibitors in Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of 107,126 Patients

Current Vascular Pharmacology ◽

10.2174/1570161116666180123092054 ◽

2019 ◽

Vol 17 (2) ◽

pp. 191-203

Author(s):

Oliver Brown ◽

Jennifer Rossington ◽

Gill Louise Buchanan ◽

Giuseppe Patti ◽

Angela Hoye

Keyword(s):

Systematic Review ◽

Acute Coronary Syndromes ◽

Meta Analysis ◽

Indirect Comparison ◽

Bleeding Risk ◽

Cardiovascular Death ◽

P2y12 Inhibitors ◽

Significant Difference ◽

Coronary Syndromes ◽

Randomised Controlled

Background and Objectives: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. Methods: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. Results: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. Conclusion: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

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