New fuel to the clopidogrel controversy: A study published online yesterday in JACC found that new P2Y12 inhibitors decrease mortality after PCI compared to clopidogrel, in particular for PCI in STEMI patients. In a meta-analysis involving a total of 48,599 patients in eight studies between 1980 and 2010, new P2Y12 inhibitors significantly reduced odds of death, and in PCI patients, the inhibitors reduced major cardiac events by 18% and stent thrombosis by 40%. Study authors conclude:

“In PCI patients, new P2Y12 inhibitors decrease all-cause mortality and major ischemic events. The net benefit is particularly marked in PCI for STEMI patients, in which there is no significant increase in major bleeding when compared with clopidogrel.”

The FDA earlier this year placed a black box warning on clopidogrel, warning physicians that some patients’ genetic makeup can affect their response and put them at risk for serious adverse events. Given that “no single study has shown a decrease in” the single hard endpoint of “mortality with clopidogrel when used in the setting of PCI or in STEMI patients treated by PCI” (according to the JACC study), cardiovascular professionals may soon find increasing appeal in utilizing these newer P2Y12 inhibitors as they become approved by the FDA. These agents theoretic appeal is that their pharmacological profiles differ from clopidogrel – there’s less concern of genetic variations causing uncertain anti-platelet activity and they have the additional desirable features of reversibility of the anti-platelet effect, and now, most importantly, evidence from this new meta-analysis of decreased mortality post PCI in ACS patients.

How do you think this new study will impact your clinical practice?  Is a single meta-analysis study with its inherent methodological weaknesses enough to cause a major change in the clinical practice of the use of thienopyridines?