Adjunctive pharmacotherapy during PCI

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Chapter 6 Adjunctive pharmacotherapy during PCI

KEY POINTS

TABLE 6.1 DOSING SUMMARY OF ADJUNCTIVE MEDICATIONS DURING PCI

SUMMARY OF ADJUNCTIVE MEDICATIONS
Drug Dose
Antithrombin agents
Unfractionated Heparin (UFH) With GP IIb/IIIa − 60–70 U/kg IV to target ACT >200–225 sec
Without GP IIb/IIIa − 100U/kg IV to target ACT >300 sec
LMWH (enoxaparin) 0.75 mg/kg IV
Bivalirudin (Angiomax®) 0.75 mg/kg bolus, 1.75 mg/kg·hr infusion
Antiplatelet agents
Aspirin 75–162 mg po qd
clopidogrel (Plavix®) 300–600 mg loading dose
75 mg po qd
Minimum of one month for BMS, 3–6 mo for DES
ticlopidine (Ticlid®) 250 mg po bid × 2–4 weeks, optional 500 mg po loading dose
abciximab (ReoPro®) 0.25 mg/kg bolus 0.125 mcg/kg·min (max 10 mcg/min) × 12 hrs post PCI
eptifibatide (Integrilin®) 180 mcg/kg bolus, 2.0 mcg/kg·min infusion for 72–96 hrs
For PCI, second 180 mcg/kg bolus administered ten minutes after first bolus
tirofiban (Aggrastat®) 0.4 mcg/kg load × 30 minutes, then 0.1 mcg/kg·min × 48–96 hrs
GPIIb/IIIa – glycoprotein IIb/IIIa inhibitor
U – units
IV – intravenous
ACT – activated clotting time
BMS – bare metal stent
DES – drug-eluting stent
mcg – microgram
kg – kilogram
PCI – percutaneous coronary intervention
min – minute
max – maximum

THIENOPYRIDINES

The thienopyridine class includes ticlopidine (Ticlid®) and clopidogrel (Plavix®) which both exert antiplatelet activity through irreversible blockade of the P2Y12 ADP receptor. Initial trials37 establishing the additive value of thienopyridines to aspirin were conducted with ticlopidine and demonstrated a reduction in relevant clinical endpoints when compared to warfarin-based therapy. Following its success in the CAPRIE trial,8 clopidogrel was compared to ticlopidine in a head-to-head trial of patients undergoing PCI. This CLASSICS trial9 demonstrated equivalent efficacy in the reduction of cardiac endpoints but that clopidogrel had a significantly superior safety profile with little gastrointestinal intolerance or bone marrow suppression.

Once established as the preferred thienopyridine, investigators pursued the application of clopidogrel in the acute coronary syndromes (ACS), specifically non-ST-segment elevation (NSTE) ACS in the CURE trial.10 As a substudy of CURE, PCI-CURE11 detailed the outcomes of the 2638 patients who underwent PCI following pretreatment with clopidogrel or placebo for a median treatment duration of six days. Patients in the active arm experienced a durable reduction in major adverse cardiac events from the initial 30 days through 12 months of follow-up suggesting that pretreatment with clopidogrel was responsible for the observed difference. As the management of ACS included an increasing number of patients undergoing early PCI, concerns arose about the effect of the duration and dosage of clopidogrel pre-treatment. Compared to the median clopidogrel pre-treatment of six days in PCI-CURE, the CREDO trial12 evaluated the efficacy of pre-treatment 3–24 hours prior to elective PCI. A loading dose of 300 mg more than six hours before stent deployment demonstrated a trend toward lower cardiac endpoints. The loading dose of clopidogrel in PCI has been further investigated given the frequency of early intervention in the NSTE-ACS population. The ARMYDA-2 trial13 recruited 255 patients who were treated with a loading dose of 600 mg (vs. 300 mg) administered 4–8 hours before PCI and demonstrated reduced periprocedural myocardial infarctions without an increased risk of bleeding. The ISAR-REACT14 trial also evaluated the increased 600 mg clopidogrel loading dose (given as late as two hours prior to PCI) and found no benefit of added IIb/IIIa receptor blockade in the setting of low-risk PCI.

With the introduction of drug eluting stents, there was a concomitant shift in the recommended minimum duration of therapy following stent deployment. Patients who received bare metal stents typically were continued on thienopyridine therapy for a minimum of 30 days – a duration which reflected the time necessary to re-endothelialize the stented arterial segment. In addition to reducing the incidence of neointimal hyperplasia, both sirolimus and paclitaxel eluting stents delay luminal re-endothelialization to varying degrees. There is currently a Class I (Level of Evidence B) recommendation from the ACC/AHA to continue clopidogrel therapy for three months following sirolimus eluting and six months following paclitaxel eluting stents.15 Following the durable benefit seen in CURE and CREDO (Fig. 6.1), many operators advise continuation of dual antiplatelet therapy with aspirin and clopidogrel for 9–12 months or more after stent placement.