Risk of stroke lower with potent P2Y12 inhibitors vs clopidogrel in Chinese ACS patients

A retrospective study of over 6,000 Chinese patients with acute coronary syndrome (ACS) who underwent first-ever percutaneous coronary intervention (PCI) has shown that use of potent P2Y12 inhibitors, such as ticagrelor and prasugrel, is associated with lower risk of stroke than clopidogrel.

“Stroke occurs in 1–4 percent of patients within the first year after ACS. The mortality rate is high [up to 36 percent], with 60 percent of survivors reporting poor functional outcomes,” wrote the researchers. “While dual antiplatelet therapy involving aspirin and a P2Y12 inhibitor is standard in patients with ACS, data on the effect of different P2Y12 inhibitors with regard to ischaemic and haemorrhagic stroke in East Asians are lacking – in spite of this group having different thrombotic and bleeding profiles compared with White patients.” [N Engl J Med 2009;361:1045-1057; J Am Heart Assoc 2021;doi:10.1161/JAHA.120.017693; Lancet 2017;390:810-820; Curr Cardiol Rep 2014;doi:10.1007/s11886-014-0485-4]

In this retrospective cohort study, researchers analyzed data from 3,110 pairs of propensity score–matched ACS patients from 14 hospitals in Hong Kong who underwent first-ever PCI between 2010 and 2017 and were either on a potent P2Y12 inhibitor (ie, ticagrelor or prasugrel) or clopidogrel. The mean age was 61.5 years and 15.1 percent of patients were women. [Stroke Vasc Neurol 2022;doi:10.1136/svn-2021-001294]

The primary outcome of ischaemic stroke occurred in 35 patients (1.13 percent) on potent P2Y12 inhibitors and 61 patients (1.96 percent) on clopidogrel, corresponding to a respective annualized risk of 1.15 percent and 2.02 percent (hazard ratio [HR], 0.57; 95 percent confidence interval [CI], 0.37 to 0.87; p=0.008). The annualized risk of composite thrombotic events was lower in the potent P2Y12 inhibitor group than the clopidogrel group (HR, 0.77; 95 percent CI, 0.66 to 0.90; p=0.001), and so was the risk of myocardial infarction (HR, 0.71; 95 percent CI, 0.59 to 0.87; p=0.001), while the risk of all-cause mortality was similar across groups (HR, 1.17; 95 percent CI, 0.87 to 1.56; p=0.30).

The primary safety endpoint of annualized risk of intracranial haemorrhage (ICH) was similar across both groups (HR, 0.65; 95 percent CI, 0.34 to 1.25; p=0.20). Other major bleeding outcomes were also similar.

The two groups had similar duration of P2Y12 inhibitor use, but more patients in the potent P2Y12 inhibitor group transitioned to clopidogrel than vice versa.

“The choice of P2Y12 inhibitors for Asian patients with ACS is a real dilemma. Asians have a higher risk of ICH and cerebral microbleeding, but a lower risk of major adverse cardiac events after PCI, which is an argument in favour of clopidogrel use, since both ticagrelor and prasugrel have been linked to increase in fatal ICH in certain subgroups. However, approximately 65 percent of East Asians carry a CYP2C19 loss-of-function allele that may result in impaired metabolic activation of clopidogrel, which is supportive of more liberal use of potent P2Y12 inhibitors,” commented the researchers. [N Engl J Med 2007;357:2001-2015; Lancet Neurol 2010;9:167-176; Neurology 2019;92:e1086-1097]

“Our data indicate that Chinese patients may benefit from potent P2Y12 inhibitors for the purpose of ischaemic stroke prevention, without incurring excess bleeding risk. However, these findings require confirmation in a randomized clinical trial dedicated to Asian patients,” they concluded.