Safe de-escalation of antiplatelet therapy in an elderly patient with ACS following PCI
History and presentation
A 75-year-old female, with a history of hypercholesterolaemia, impaired fasting glucose and a psychiatric disorder. The patient was hospitalized for pyelonephritis in January 2019, during which she complained of acute chest pain and remained haemodynamically stable. Electrocardiogram revealed abnormalities indicative of acute coronary syndrome (ACS), and blood test showed elevated troponin level. Echocardiogram showed normal left ventricular ejection fraction and mild hypokinesia in the area of the left anterior descending (LAD) artery. Coronary angiogram via the radial artery detected a thrombotic lesion in the LAD artery.
Treatment and response
Percutaneous coronary intervention (PCI) was performed with implantation of a new-generation thin-strut drug-eluting stent (DES). The patient was started on dual antiplatelet therapy (DAPT) with aspirin (100 mg/day) plus ticagrelor (90 mg BID) and was discharged a week after the PCI procedure.
During routine follow-up 1 month after DAPT initiation, the patient complained of frequent and extensive bruising, which was a major concern for her and her family. The patient also had compliance issues with DAPT, which was taken along with other medications (including a statin, an angiotensin receptor blocker, a proton pump inhibitor and multiple psychotropic medications) for her comorbidities. The DAPT regimen was de-escalated to a fixed-dose combination tablet of clopidogrel 75mg daily plus aspirin 100mg daily to reduce the daily pill burden and help improve compliance.
Platelet reactivity test (by VerifyNow platelet function assay) during a second follow-up 1 month later showed relatively low on-treatment platelet reactivity (80 P2Y12 reaction units), which suggested a strong response to clopidogrel treatment. The patient and her family continued to express concern over the bruising despite reported improvement. DAPT with clopidogrel plus aspirin was de-escalated to clopidogrel monotherapy (75 mg/day) without aspirin.
At the latest follow-up in June 2019, the patient reported improvement in exercise tolerance and overall well-being, and no longer complained of bruising or compliance issues.
Improved PCI technique and the advent of newest-generation DES with thinner struts have helped in lowering the risk of stent thrombosis, making de-escalation of antiplatelet therapy a viable option in managing ACS patients following PCI. The TOPIC trial, an open-label, single-centre, randomized study involving 646 Caucasian ACS patients requiring PCI, showed that switching to a de-escalated DAPT regimen with aspirin plus clopidogrel after 1 month of DAPT with aspirin plus a more potent P2Y12 inhibitor (ie, ticagrelor or prasugrel) significantly reduced bleeding events at 1 year compared with unchanged DAPT (23.5 percent vs 9.3 percent; hazard ratio [HR], 0.39; p<0.01), without increasing ischaemic events (11.5 percent vs 9.3 percent; HR, 0.80; p=0.36). (Table)1
Recent trials such as STOPDAPT-2 and SMART-CHOICE have evaluated the effect of de-escalation of antiplatelet therapy in Asian patients with ACS, who are known to have different risks of bleeding and thrombosis compared with Caucasian patients. STOPDAPT-2, a multicentre, open-label, randomized trial showed that 1 month of DAPT with aspirin plus clopidogrel followed by de-escalation to clopidogrel alone resulted in a significantly lower rate of a composite of cardiovascular and bleeding events vs 12-month DAPT.2 SMART-CHOICE, an open-label, noninferiority, randomized study, showed that after 3 months of DAPT (aspirin plus either clopidogrel, prasugrel or ticagrelor), de-escalated antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor alone) resulted in a similar rate of major adverse cardiac and cerebrovascular events at 12 months vs prolonged DAPT.3 (Table)
Another multicentre, open-label, randomized trial (TROPICAL-ACS) showed that platelet function testing (PFT)– guided de-escalation of antiplatelet therapy after PCI (ie, 1 week of prasugrel plus 1 week of clopidogrel, followed by PFT-guided maintenance therapy with either prasugrel [for patients with high on-treatment platelet reactivity (HPR)] or clopidogrel [for patients with no HPR] from day 14 after hospital discharge) was noninferior to standard treatment with prasugrel for 1 year (control group) in terms of combined ischaemic and bleeding events (9 percent vs 7 percent; HR, 0.81; p=0.0004 for noninferiority; p=0.12 for superiority).4
These clinical trials provided evidence to support de-escalation from DAPT to P2Y12 inhibitor monotherapy (eg, clopidogrel) as a viable and safe antiplatelet therapeutic option in patients with ACS following PCI, as well as the value of PFT in guiding antiplatelet therapy de-escalation in clinical practice. Ongoing and future clinical trials will continue to examine the feasibility and safety of antiplatelet therapy de-escalation (including treatment without aspirin) in lowering the bleeding risk and pill burden of ACS patients undergoing PCI.
Multiple factors, including thrombotic and bleeding risks over the course of disease management, pill burden, patient compliance, age, physical and mental status, and potential side effects and affordability of medications, need to be considered in optimizing antiplatelet therapy in ACS patients requiring PCI. This case study illustrated the successful de-escalation of antiplatelet therapy in an elderly ACS patient who had undergone PCI with implantation of a newest-generation DES and demonstrated low thrombus burden during the procedure. Stepwise de-escalation from an intensive antiplatelet regimen (with ticagrelor plus aspirin) to subsequent clopidogrel monotherapy without aspirin effectively and safely managed the risks of both thrombosis and bleeding in our patient. This strategy also helped resolve her compliance issues and bruising problems, though only classified as minor bleeding, nonetheless were a source of anxiety for the patient and her family, and thus a potential cause for non-compliance.