DAPT after PCI: Fracture risk lower with ticagrelor vs clopidogrel in Chinese ACS patients

A territory-wide, retrospective cohort study in Hong Kong has shown that dual antiplatelet therapy (DAPT) with ticagrelor is associated with a lower risk of major osteoporotic fractures (MOF) than clopidogrel in Chinese patients with acute coronary syndrome (ACS) who underwent first-ever percutaneous coronary intervention (PCI).

ACS patients are at increased risk of fractures, especially when receiving clopidogrel, a P2Y₁₂ inhibitor commonly used in DAPT. An observational study demonstrated that in ACS patients, clopidogrel use is associated with a 50 percent increased risk of fractures vs nonuse. [Bone 2013;52:562-567; J Intern Med 2012;272:385-393]

“However, clinical data are lacking on fracture risk associated with another P2Y₁₂ inhibitor, ticagrelor. We conducted this retrospective cohort study to compare fracture risk associated with ticagrelor and clopidogrel in PCI-treated Chinese ACS patients,” the researchers wrote. [J Endocrinol Invest 2023;doi:10.1007/s40618-023-02205-1]

From a territory-wide PCI registry, the researchers retrieved data of 19,788 patients aged ≥18 years who were prescribed DAPT with ticagrelor or clopidogrel after their first-ever PCI between 1 January 2010 and 31 December 2017. In this study cohort, 18,654 patients had complete data for propensity score matching (PSM).

After PSM, the primary analysis included 6,036 patients (3,018 ticagrelor users and 3,018 clopidogrel users). These patients had a mean age of 61.4 years (age >65 years, 36.3 percent), and the majority were male (84.1 percent) and users of proton pump inhibitors (82.2 percent). Diabetes was present in 26.6 percent of patients, while 16.4 percent had chronic kidney disease (CKD; defined as estimated glomerular filtration rate <60 mL/min/1.73 m²). Vitamin D and/or calcium supplements were used by 5.7 percent of patients, while 0.2 percent received bisphosphonates or other anti-osteoporosis medications. Rates of prior falls and prior MOF were 9.2 percent and 4.4 percent, respectively.

Over a median follow-up of 6.5 years, the primary outcome of MOF occurred in 59 ticagrelor users (2.0 percent) and 119 clopidogrel users (3.9 percent). The corresponding annualized risk of MOF was 0.34 percent and 0.56 percent. The use of ticagrelor was associated with a lower risk of MOF vs clopidogrel (hazard ratio [HR], 0.60; 95 percent confidence interval [CI], 0.44–0.83; p=0.002).

In the secondary analysis, the risk of upper limb fractures was significantly reduced with ticagrelor vs clopidogrel (HR, 0.53; 95 percent CI, 0.34–0.85; p=0.008). Results also showed trends towards lower risks of clinical vertebral fractures (HR, 0.61; 95 percent CI, 0.29–1.27; p=0.19) and hip fractures (HR, 0.65; 95 percent CI, 0.40–1.06; p=0.087) with ticagrelor vs clopidogrel.

“Possibly due to the low event rates in the vertebrae and hip, the lower fracture risks associated with ticagrelor vs clopidogrel at these two sites did not reach statistical significance,” the researchers noted.

Notably, subgroup analyses demonstrated that the reduction in MOF risk with ticagrelor vs clopidogrel was consistent across age, sex, diabetes or CKD status, and fracture history. Results of the primary analysis were further confirmed in sensitivity analyses of the patient cohort with complete data before PSM, as well as the entire study cohort including patients with missing data.