Tuesday, December 13, 2011

Highlights from the 2011 Guidelines for Percutaneous Coronary Intervention (PCI)

While a significant portion of the 2011 update to the ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention (PCI) [1] focus on revascularization strategies, several important medication changes are also worth highlighting, including the following:  
Aspirin 81 mg is reasonable for chronic maintenance therapy following PCI. Clinicians should no longer feel bound to use higher maintenance doses of aspirin following PCI, as the 2011 guidelines now recognize 81 mg as being an adequate dose for long-term maintenance therapy in patients who have received a loading dose of 325 mg.

Prior to this most recent update, higher doses of aspirin were recommended for a specific length of time based on the type of stent placed.  This practice was largely conventional (i.e., based on the dosing strategies used in stenting trials), rather than evidence indicating higher doses were more efficacious. In fact, a meta-analysis from Antithrombotic Trialists' Collaborative [2] indicated that higher doses were probably associated with more harm than good, although few trials had looked specifically at lower aspirin doses and even fewer included significant numbers of patients receiving PCI.  However, the practice of using higher maintenance doses of aspirin had been all but abandoned outside of North America, a fact further highlighted in the controversy that erupted following the publication of PLATO, where higher aspirin doses were thought to attenuate the effects of ticagrelor in North American patients [3].

Interestingly, the trial that appeared to put the aspirin dosing issue to rest (CURRENT OASIS-7) is not referenced in the updated guidelines. As I summarized in a previous post, CURRENT OASIS-7 demonstrated in a randomized prospective fashion that higher doses of aspirin were not associated with improved outcomes in patients with acute coronary syndromes with or without PCI [4].  

Clopidogrel remains a cornerstone in the management of patients receiving PCI. Although prasugrel and ticagrelor may be selected as an alternative to clopidogrel, the latter remains a mainstay of dual antiplatelet therapy.  Each agent is given a similar recommendation in patients receiving stents (Class I, Level of Evidence B), which differs from the 2011 European guidelines for the management of non-ST segment elevation myocardial infarction (NSTEMI), where clopidogrel is recommended only in those patients who are not candidates for prasugrel or ticagrelor.  With the patent for clopidogrel set to expire in the late spring of 2012, it will undoubtedly remain popular in the US for quite some time.

The results of CURRENT OASIS-7 are again omitted from the 2011 PCI guidelines during the discussion of clopidogrel dosing, where no mention of double-dose clopidogrel (150 mg) for days 2-7 following PCI can be found (despite a Class IIb recommendation for this practice in the US 2011 update to the UA/NSTEMI guidelines). 

Ticagrelor recognized as an alternative to clopidogrel for the first time in the US. As described above, the 2011 PCI guidelines recognize ticagrelor as an alternative to clopidogrel following PCI, marking its first formal inclusion in US guidelines.   

Dual antiplatelet therapy recommended for at least 12 months following PCI. The appropriate duration of dual antiplatelet therapy is recognized as being at least 12 months in this most recent update, with shorter durations acceptable for patients at increased risk of bleeding or in whom bare metal stents are used.  Given the recognizable risk of very late stent thrombosis (i.e., > 1 year from implantation) associated with drug-eluting stents, longer durations may be considered, although no formal length of time is provided.   

Provisional use of intravenous glycoprotein IIb/IIIa inhibitors remains an option in patients not being anticoagulated with bivalirudin. The use of glycoprotein IIb/IIIa inhibitors is recommended in patients who are not being anticoagulated with bivalirudin, with stronger evidence to support this practice in patients who have not already been adequately loaded with clopidogrel.  Adding to the evidence that emerged from the REPLACE-2 and ACUITY trials, the combination of unfractionated heparin (UFH) and a glycoprotein IIb/IIIa inhibitor was shown in ISAR-REACT 4 to be no better than bivalirudin alone in patients with NSTEMI being managed with an early invasive strategy and receiving an adequate loading dose of clopidogrel [5].  Notably, the combination of UFH and a glycoprotein IIb/IIIa inhibitor was also associated with a nearly two-fold increase risk of major bleeding compared to bivalirudin alone.   

The administration of high-dose statins should be considered prior to PCI. It has already been known for some time that high-dose statins are associated with improved outcomes early in the management of acute coronary syndromes.  However, the results of the NAPLES II trial [6] indicate that some of these improvements may be observed as early as hours after PCI, only adding to the evidence that high potency statins likely confer a benefit independent of their lipid-lowering capabilities.

Oral N-acetylcysteine is no longer recommended for renoprotection prior to cardiac catheterization. Given the lack of benefit observed across a number of trials, the administration of N-acetylcysteine is no longer recommended for the purposes of preventing contrast-induced acute kidney injury. Adequate hydration remains the only Class I recommendation in the 2011 guidelines, although no specific fluid type is mentioned (i.e., normal saline vs. sodium bicarbonate).

We were fortunate to have the opportunity to meet with our interventional cardiologists earlier this week, where we discussed several of these updated recommendations and how best to implement them at our institution. Processes for updating our order sets and standards of practice are already underway.

  1. Levine GN, Bates ER, Ting HH, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011 Dec 6;58(24):e44-e122.
  2. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86.
  3. Mahaffey KW, Wojdyla DM, Wallentin L, et al; PLATO Investigators. Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2011 Aug 2;124(5):544-54.
  4. Mehta SR, Tanguay JF, Yusuf S, et al; CURRENT-OASIS 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010 Oct 9;376(9748):1233-43.
  5. Kastrati A, Neumann FJ, Mehilli J, et al; ISAR-REACT 4 Trial Investigators. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med. 2011 Nov 24;365(21):1980-9.
  6. Briguori C, Visconti G, Colombo A, et al. Novel approaches for preventing or limiting events (Naples) II trial: impact of a single high loading dose of atorvastatin on periprocedural myocardial infarction. J Am Coll Cardiol. 2009 Dec 1;54(23):2157-63.

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