Strategic de-escalation of DAPT to reduce bleeding risk in ACS following PCI
History and presentation
This is a case of a 70-year-old mildly obese gentleman with a history of chronic hypertension and cigarette smoking. He presented in April 2020 with angina and progressive dyspnoea for 3 months. Initial examination detected pitting oedema and signs of mitral regurgitation and acute decompensated heart failure. Electrocardiogram revealed normal sinus rhythm with heart rate of approximately 95 beats per minute, diffuse ST depression and T wave inversion in the anterior precordial leads V1–V5. Blood tests showed elevated levels of cardiac troponin I (>0.7 ng/mL) and fasting LDL-cholesterol (3.6 mmol/L), and prediabetic levels of fasting blood glucose (6.2 mmol/L) and HbA1c (6.1 percent).
The patient was suspected of having non-ST elevation acute coronary syndrome (NSTE-ACS) and was admitted to the hospital for further testing. Chest X-ray showed mild cardiomegaly and signs of mild interstitial pulmonary oedema. Echocardiogram detected reduced left ventricular ejection fraction (50 percent), with evidence of enlarged left atrium and left ventricular diastolic dysfunction, and hypokinesia in the anterior wall, distal interventricular septum and apical region, indicative of ACS due to occlusion of the left anterior descending (LAD) coronary artery.
Early coronary angiography revealed subtotal occlusion of the proximal LAD coronary artery, and mild stenosis of the left circumflex artery and right coronary artery, which confirmed the diagnosis of NSTE-ACS.
Treatment and response
The patient was started on dual antiplatelet therapy (DAPT) with ticagrelor (180 mg loading dose, followed by 90 mg BID) and aspirin (100 mg QD) in April 2020. Symptoms of angina and dyspnoea improved with concomitant administration of a statin, an H2 antagonist, oral nitrates and short-term diuretics.
Percutaneous coronary intervention (PCI) was performed with implantation of a drug-eluting stent to the LAD coronary artery. The patient was discharged from the hospital 2 days after PCI and was free from symptoms of angina and dyspnoea.
However, the patient experienced bruising in the limbs and periodic haemorrhoidal bleeding soon after hospital discharge. The DAPT regimen was de-escalated to clopidogrel (75 mg QD) plus aspirin (80 mg QD) 1 month after treatment initiation. He responded well to clopidogrel, with bruising and haemorrhoidal bleeding significantly reduced. He did not experience any ischaemic events and is currently able to resume exercise and other lifestyle modifications for improving overall health.
DAPT with a P2Y12 inhibitor and aspirin is currently recommended by the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) in the management of ACS (including NSTE-ACS) in patients who undergo PCI.1,2 (Figure)
It is important to balance ischaemic risk with bleeding risk when considering the choice of and treatment duration with P2Y12 inhibitors.1,2
Switching or de-escalating to clopidogrel may be considered in patients with a history of ACS who develop drug intolerance or side effects with the use of potent P2Y12 inhibitors (ie, prasugrel and ticagrelor), which are known to be associated with increased bleeding risk. In these patients, clopidogrel is a viable therapeutic option to minimize bleeding risk without compromising antithrombotic efficacy after PCI.1,2
The open-label, single-centre, randomized TOPIC trial showed that patients who were switched from a newer P2Y12 inhibitor plus aspirin to clopidogrel plus aspirin after 1 month (ie, the switched group) had a significantly lower rate of primary outcome (a composite of cardiovascular death, urgent revascularization, stroke and bleeding [defined by Bleeding Academic Research Consortium (BARC) classification ≥2]) compared with patients who remained on DAPT with a newer P2Y12 inhibitor (ie, the unchanged group) at 1 year after ACS (13.4 percent vs 26.3 percent; hazard ratio [HR], 0.48; p<0.01).3 There was also significantly less bleeding (BARC ≥2) in the switched group vs unchanged group (4 percent vs 14.9 percent; HR, 0.3; p<0.01), without an increase in reported ischaemic events.3
Evidence suggests that Caucasian patients have different ischaemic and bleeding risk profiles compared with East Asian patients, who were often under-represented in clinical trials assessing the use of P2Y12 inhibitors in ACS patients undergoing PCI.4 Recent update of an expert consensus statement (originally developed by the World Heart Federation) to help antiplatelet therapeutic strategies in East Asian patients recommends the use of clopidogrel with aspirin as a reasonable DAPT choice for ACS (during the chronic phase) or elective PCI among the East Asian population.5 According to the consensus statement, the use of standard-dose potent P2Y12 inhibitors (ie, prasugrel and ticagrelor) should be carefully considered in East Asian patients with ACS who may have increased bleeding risk (eg, elderly patients, those with prior stroke, low body weight or recurrent nuisance bleeding episodes).5 When discontinuation of potent P2Y12 inhibitors is required, switching to clopidogrel (after clopidogrel bolus) may be a viable option for East Asian patients with ACS.5
In a recent retrospective single-centered cohort study, Asian patients (with ST-elevated myocardial infarction) (n=349) who switched from DAPT with ticagrelor plus aspirin to clopidogrel within 1 year after PCI had less clinically significant bleeding (CSB, BARC ≥2) vs those who remained on ticagrelor (7.8 percent vs 8.5 percent; HR, 0.298; p=0.047), without an increase in the rate of the composite outcome of major adverse cardiac and cerebrovascular events and CSB (10 percent vs 13.8 percent; HR, 0.484; p=0.114).6 The authors also noted that de-escalation from ticagrelor to clopidogrel could translate to cost savings for Asian patients without compromising safety and efficacy.6
Our experience in Hong Kong has shown that clopidogrel is a cost-effective option that can control bleeding risk without increasing ischaemic risk in ACS patients. This can reduce patients’ financial burden since newer antiplatelet therapies are often not reimbursed in Hong Kong.
Optimizing the clinical outcome of ACS following PCI requires detailed clinical investigation, prompt diagnosis, and timely interventional strategies tailored to individual patients. This case illustrates the clinical benefits of promptly switching antiplatelet therapy from a potent P2Y12 inhibitor to clopidogrel following PCI in an elderly ACS patient, who had multiple cardiovascular risk factors. Our patient responded well to de-escalation of DAPT with ticagrelor to DAPT clopidogrel, minimized bleeding without causing ischaemic events, and enabled him to resume normal daily routine and activities.