Aspirin stents

Bertrand ME, Rupprecht HJ, Urban R Gershlick AH, Investigators FT, Double-blind study ofthe safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 2000 102 624-629,... 

For patients undergoing primary PCI, clopidogrel is administered as a 300-to 600-mg loading dose followed by a 75 mg/day maintenance dose, in combination with aspirin 325 mg once daily, to prevent subacute stent thrombosis and long-term cardiovascular events. 

The risk of major bleeding from chronic aspirin therapy is approximately 2% and is dose related. Therefore, after an initial dose of 325 mg, chronic low doses of 75 to 81 mg are recommended unless a stent is placed. 

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, dopidogrel, and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopido-grel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

One of the significant factors promoting late stent thrombosis has been found to be premature discontinuation of dual antiplatelet therapy (aspirin and clopidrogel). In an analysis of 4,666 of patients undergoing initial PCI with BMS or DES, researchers from the Duke Heart center reported that longterm risk for death and major cardiac events was significantly increased among patients in the DES... 

Clopidogrel is indicated for prevention of vascular ischaemic events in patients with symptomatic atherosclerosis. It is also used, along with aspirin, for the prevention of thromboembolism after placement of an intracoronary stent. Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so that a loading-dose is usually administered. Although rare, severe neutropenia and also thrombotic thrombocytopenic purpura may occur. 

Van Belle E, McFadden EP Lablanche JM, Bauters C, Hamon M, Bertrand ME. Two-pronged antiplatelet therapy with aspirin and ticlopidine without systemic anticoagulation an alternative therapeutic strategy after bailout stent implantation. Coron Artery Dis I 995 6 341-345. 

Bertrand ME, Legrand V Boland J, et al. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting, The full anti coagulation versus aspirin and ticlopidine (fantastic) study. Circulation I 998 98 1 597-1603. 

Urban P Macaya C, Rupprecht HJ, et al. Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS). Circulation 1998 98 2126-2132. 

Ahn JC, Song WH, Kwon JA, et al. Effects of cilostazol on platelet activation in coronary stenting patients who already treated with aspirin and clopidogrel. Korean J Int Med 2004 19 230-236. 

Eptifibatide (Integrelin), a cyclic heptapeptide based on a peptide sequence in snake venom, is a GPIIb/llla inhibitor used in conjunction with heparin and aspirin for the treatment of ACS or in PCI, with or without stenting and clopidogrel (Table I). 

PCI was performed using standard techniques (6,30). All 100 patients received one or more identical close cell-stent design. The same stent design was used in order to avoid potential bias with stent selection in both groups. All patients received 325 mg/day of aspirin indefinitely and clopidogrel as a loading dose of 300 mg on the day of the procedure and 75 mg/day thereafter for one month. Statins were given to all patients indefinitely. 

Mehran R, Aymong ED, Ashby DT et al. Safety of an aspirin-alone regimen after intracoronary stenting with a heparin-coated stent final results of the HOPE (HEPACOAT and an Antithrombotic Regimen of Aspirin Alone) study. Circulation 2003 108(9) 1078-1083. 

Late stent thrombosis (LST) after the use of DES is a rare complication. The SIR.TAX (7) trial has shown LST rates of 0.5% to 0.9% using DES. A case series (8) of four patients with LST who had stopped taking aspirin many months after DES implant has been reported. Registry data of DES use (9) reported a 0.7% late thrombosis rate, half of which patients died as a consequence. 

The addition of ticlopidine to aspirin has been shown to have a synergistic effect on the inhibition of platelet aggregation after stent insertion (6), and this combination has also been found to be superior in terms of prevention of in-stent thrombosis to both aspirin alone and aspirin combined with warfarin (7). However, due to the rare but serious side effect of agranulocytosis associated with ticlopidine (8), and its slow onset of action, ticlopidine is no longer used in most countries. The combination of clopidogrel and aspirin has been proved to be as effective as aspirin and ticlopidine in the prevention of intrastent thrombosis (9). 

Cilostazol is a phosphodiesterase inhibitor that reduces platelet aggregation, vascular smooth muscle proliferation and also has vasodilatory effects. Earlier studies comparing cilostazol and aspirin to ticlodipine and aspirin identified no significant increase in the subacute stent thrombosis rate (21-23). Indeed, the latter has been supported by comparison of this combination to clopidogrel and aspirin (24). Two recent trials, however, have demonstrated that a much higher proportion of patients develop subacute stent thrombosis when taking cilostazol as compared with ticlodipine (25,26). The data from these trials are summarized in Table I. 

Rupprecht HJ, Darius H, Borkowski U, et al, Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination after stent implantation. Circulation 1998 97(1 I) 1046-1052. 

Muller C, Buttner HJ, Petersen J, Roskamm H. A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary-artery stents. Circulation 2000 101 (6) 590—603. 

Claeys MJ, Van der Planken MG, Bosmans JM, et al. Does pretreatment with aspirin and loading dose clopidogrel obviate the need for glycoprotein llb/llla antagonists during elective coronary stenting A focus on peri-procedural myonecrosis. Eur Heart J 2005 26(6) 567-575. 

The most important safety concerns are the potential for perforation which could result in tamponade or compromise of collaterals which can result in infarction. In current PCI practice with its reliance on drug eluting stent (DES), dual antiplatelet therapy with aspirin (ASA) and a thienopyridine (usually clopidogrel) is standard. These should be used in all patients. Pre-procedure administration of the thienopyridine should be given, if possible. 

---