Dual antiplatelet therapy in coronary artery disease: A case-based approach
ABSTRACTCurrent guidelines support dual antiplatelet therapy with aspirin and clopidogrel (Plavix) in a number of clinical scenarios, ie, in ST-segment-elevation myocardial infarction (MI), non-ST-elevation MI, and percutaneous coronary intervention. The guidelines are based on strong evidence from several large randomized clinical trials over the last 10 years. The authors present several cases to show how to put this evidence into day-to-day clinical practice.
KEY POINTS
- Dual antiplatelet therapy is recommended after ST-elevation MI or non-ST-elevation acute coronary syndromes, with aspirin indefinitely and clopidogrel for up to 1 year.
- Dual antiplatelet therapy is recommended for at least 1 month after placement of a bare-metal stent and for at least 1 year (or possibly indefinitely) after placement of a drug-eluting stent.
- There is no compelling indication for clopidogrel in patients with chronic coronary artery disease.
- Compared with clopidogrel, prasugrel (Effient) is associated with lower rates of MI, urgent target-vessel revascularization, and in-stent thrombosis, but at the cost of a higher risk of major bleeding.
CASE 3: BARE-METAL STENT PLACEMENT
A 62-year-old man with a history of hypertension, diabetes, and hyperlipidemia presents to his primary care physician’s office with stable-effort angina that is not responding to an excellent anti-ischemic regimen and is affecting his quality of life. He is referred for coronary angiography, which reveals 80% stenosis of the proximal left circumflex artery. He undergoes a percutaneous coronary intervention with placement of a bare-metal stent.
How long should he be on clopidogrel? And what if a drug-eluting stent had been placed instead of a bare-metal stent?
Dual therapy after bare-metal stent placement
Dual antiplatelet therapy with clopidogrel and aspirin is recommended in all patients receiving a stent (Table 2). The better safety and efficacy of clopidogrel compared with ticlopidine has been established in patients receiving a coronary artery stent,12,13 and clopidogrel’s favorable safety profile soon made it the thienopyridine of choice.
The CREDO trial (Clopidogrel for the Reduction of Events During Observation)14 randomized 2,116 patients undergoing an elective percutaneous coronary intervention (bare-metal stent placement only) to receive a 300-mg loading dose of clopidogrel 3 to 24 hours before the procedure, or placebo. All patients received 325 mg of aspirin. After the intervention, all patients received clopidogrel 75 mg daily and aspirin 325 mg daily through day 28. For day 29 through 12 months, those who had received the 300-mg preprocedural loading dose of clopidogrel continued with 75 mg daily, and those who had not received clopidogrel before the procedure received placebo.
No significant difference was seen in the primary outcome for those who received pretreatment with clopidogrel; however, in a subgroup analysis, those who received clopidogrel at least 6 hours before the percutaneous coronary intervention had a 38.6% relative risk reduction (Table 1). Long-term use of clopidogrel (ie, for 12 months) was associated with an overall relative reduction of 26.9% in the combined risk of death, MI, or stroke.
PCI-CURE, an analysis of 2,658 patients in the CURE trial with non-ST-elevation acute coronary syndrome who underwent PCI,15 yielded results similar to those of CREDO, with a 31% reduction in the rate of cardiovascular death or MI at 30 days and at 9 months. Of note, however, clopidogrel was given for a median of 6 days prior to the procedure.
Comment. The minimum suggested duration of clopidogrel treatment after placement of a bare-metal stent is 1 month. However, these trial results indicate that patients who are not at high risk of bleeding should take clopidogrel for at least 12 months.
Dual antiplatelet therapy with drug-eluting stents
Although rates of in-stent restenosis are clearly lower with drug-eluting stents than with bare-metal stents, the antiproliferative effect of drug-eluting stents may delay complete endothelialization of every strut. This may contribute to late (> 1 month after placement) or very late (> 1 year) thrombosis of the stent after clopidogrel is discontinued.16–18
In 2006, the FDA indicated that dual antiplatelet therapy was needed for 6 months with paclitaxel-eluting (Taxus) stents and 3 months with sirolimus-eluting (Cipher) stents. As reports of very late stent thrombosis began to appear in 2007, concern arose over the need to extend the duration of clopidogrel treatment.
Bavry et al19 quantified the incidence of late and very late stent thrombosis in a meta-analysis of 14 clinical trials that randomized patients to receive either a drug-eluting stent (paclitaxel or sirolimus) or a bare-metal stent.19 The incidence of stent thrombosis within 30 days in this analysis was similar for both groups—4.4 per 1,000 patients vs 5 per 1,000 (relative risk 0.89; 95% CI 0.46–1.75; P = .74). However, the rate of very late stent thrombosis was significantly higher in those receiving a drug-eluting stent vs a bare-metal stent—5 per 1,000 patients treated (relative risk 5.02, 95% CI 1.29–19.52; P = .02).
The results of this and other studies led the ACC and AHA to revise their joint guidelines to recommend thienopyridine treatment for at least 1 year for patients who receive a drug-eluting stent.6,20–22 In fact, many cardiologists consider indefinite dual antiplatelet therapy in patients with a drug-eluting stent to avoid very late in-stent thrombosis, especially in patients undergoing high-risk interventions such as placement of multiple stents, bifurcation lesions, and unprotected left main trunk interventions.
Thus, when faced with a patient with a recent coronary stent implantation, the primary care physician should be aware of the type of stent and the duration of therapy recommended by the interventional cardiologist. Also, in the absence of a pressing indication, elective surgery should be deferred for 1 year after placement of a drug-eluting stent, as this would necessitate stopping clopidogrel and would increase the risk of perioperative stent thrombosis, which is associated with high rates of morbidity and death.
