William B. Hillegass, MD, MPH
Do third-generation P2Y12 inhibitors reduce mortality more than clopidogrel after percutaneous coronary intervention (PCI)?
Included studies compared third-generation P2Y12 inhibitors with clopidogrel (or with placebo before clopidogrel in the case of short half-life P2Y12 inhibitors) in populations in which > 70% of coronary patients had PCI and outcomes included mortality and bleeding. Other outcomes included major adverse cardiac events (MACE) and stent thrombosis.
MEDLINE and Cochrane Controlled Trials Register were searched from 1980 to January 2010 for full-text articles, substudies, and meeting abstracts; reference lists of relevant studies, reviews, editorials, and letters were reviewed. 8 randomized controlled trials (RCTs) (n = 48 599) met the selection criteria; 94% of patients had acute coronary syndromes (ACSs), and 84% had PCI. P2Y12 inhibitors were prasugrel (3 RCTs), cangrelor (2 RCTs), ticagrelor (2 RCTs), and elinogrel (1 RCT). Clopidogrel loading dose ranged from 300 to 600 mg.
All PCI patients: Patients allocated to third-generation P2Y12 inhibitors had lower risk for mortality, MACE, and stent thrombosis and higher risk for major bleeding than those allocated to clopidogrel (Table). Groups did not differ for stroke (0.72% vs 0.38%, P = 0.62). ST-segment elevation myocardial infarction (STEMI) patients having PCI: Patients allocated to third-generation P2Y12 inhibitors had lower risk for mortality, MACE, and stent thrombosis than those allocated to clopidogrel (Table) but higher risk for stroke (1.54% vs 1.13%, P = 0.02). Groups did not differ for major bleeding (Table).
Third-generation P2Y12 inhibitors reduce risk for mortality and increase risk for major bleeding after PCI; a similar reduction in mortality was seen in patients with STEMI, without an increased risk for major bleeding.
Third-generation P2Y12 inhibitors vs clopidogrel (clop) after percutaneous coronary intervention*
*MACE = major adverse cardiac event; STEMI = ST-segment elevation myocardial infarction; other abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from control event rates and odds ratios in article using a random-effects model. Outcomes were assessed at the longest follow-up available in each study (range 15 d to 15 mo).
†Thrombolysis In Myocardial Infarction noncoronary artery bypass graft major bleeding.
Hillegass WB. Review: Third-generation P2Y12 inhibitors reduce mortality after PCI more than clopidogrel. Ann Intern Med. 2011;154:JC3–6. doi: 10.7326/0003-4819-154-6-201103150-02006
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Published: Ann Intern Med. 2011;154(6):JC3-6.
Acute Coronary Syndromes, Cardiology, Coronary Heart Disease, Emergency Medicine, Neurology.
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