WHAT IS PEER TO PEER?
Med-IQ's new complimentary, certified continuing medical education (CME) activity,
Peer to Peer: A New Model for Improving Guideline- and Evidence-Based ACS Care, is connecting healthcare professionals from across the country. This exciting, first-of-its-kind CME series provides participants with access to acute coronary syndrome (ACS) faculty experts during personalized sessions focusing on improving ACS patient care in their practices. This real-time exchange of ideas has helped address some of the major challenges that clinical practices face in managing ACS cases.

WHAT ARE E-BRIEFS?
Each month, Med-IQ will publish a short e-brief to highlight real-world questions, opportunities for improvement, and front-line perspectives gained from these ACS Peer to Peer teleconferences. Below, you'll find the eighth of these e-briefs; in this installment, our expert faculty answer questions regarding long-term medication therapy in patients with ACS.

Secondary prevention of cardiovascular (CV) events is a key component of ACS care; however, making decisions about long-term medication therapy is not always straight-forward. Specifics for recommended post-discharge care often depend upon individual patient characteristics and needs. Moreover, data are often lacking for the optimal long-term medication therapy in patients with ACS. Below, our faculty examine maintenance dosing with thienopyridines, duration of thienopyridine use in patients with drug-eluting stents, and the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in ACS patients with renal dysfunction.

Maintenance Dosing With Thienopyridines
Question: What is the optimal maintenance dose for thienopyridines at discharge?

Answer: This is an important consideration for ACS patients regardless of the management strategy employed during hospitalization. The 2007 ACC/AHA UA/NSTEMI guidelines indicate that all medically treated UA/NSTEMI patients should be maintained on both aspirin and clopidogrel at discharge. Aspirin should be continued indefinitely, and clopidogrel (75 mg/day) should be continued for at least 1 month (Level of Evidence: A) and ideally up to 1 year (Level of Evidence: B).¹ The 2009 Joint Focused Update of the ACC/AHA guidelines for the management of STEMI and ACC/AHA/SCAI guidelines for PCI indicate that clopidogrel (75 mg/day) or prasugrel (10 mg/day) should be continued for at least 1 year post-discharge in patients who receive a bare-metal or drug-eluting stent.²

Investigators have attempted to determine whether there is benefit from increasing the clopidogrel loading dose and initial short-term maintenance dose. In the CURRENT OASIS-7 trial, more than 25,000 patients for whom PCI was planned were randomized to received doubled loading and maintenance doses of clopidogrel (600-mg loading dose, 150 mg/day for 7 days, 75 mg/day for 30 days) or the standard clopidogrel dosing regimen (300-mg loading dose followed by 75 mg/day for 30 days). Patients also received low- or high-dose aspirin therapy. Of the 25,000 patients, 7,855 did not undergo PCI either because no significant coronary artery disease was found on angiogram or the patients were scheduled for coronary artery bypass graft (CABG). For the entire study population, no significant differences were found between the two clopidogrel arms in the combined endpoint of CV death, myocardial infarction (MI), or stroke at 30 days.³ In the cohort of 17,232 patients who underwent PCI, however, there was a significant 15% reduction (HR, 0.85; 95% CI, 0.74-0.99; P = 0.036) in the combined endpoint (CV death, MI, or stroke), likely driven by a significant 22% reduction in MI (HR, 0.78; 95% CI, 0.64-0.95; P = 0.012). In addition, there was a significant 42% reduction in definite stent thrombosis (HR, 0.58; 95% CI, 0.42-0.79; P = 0.001). No significant differences were found in the rates of TIMI major bleeding, fatal bleeding, intracranial hemorrhage (ICH), or CABG-related major bleeding. However, significant increases were reported in CURRENT-defined major bleeding (HR, 1.44; 95% CI, 1.11-1.86; P = 0.006) and CURRENT-defined severe bleeding (HR, 1.39, 95% CI, 1.02-1.90; P = 0.034). ³

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Duration of Thienopyridine Use in Patients With Drug-Eluting Stents
Question: Should thienopyridine therapy be extended beyond 1 year in ACS patients with drug-eluting stents?

Answer: The appropriate duration of dual antiplatelet therapy is a topic of ongoing debate and is likely to depend on individual patient factors. Currently, information is lacking about the benefits and risks of thienopyridine therapy used beyond 15 months and the extended use of dual antiplatelet therapy in patients with drug-eluting stents.⁴

The 2009 Joint Focused Update indicates that patients who receive either a bare-metal or drug-eluting stent should receive a maintenance dose of clopidogrel (75 mg/day) for at least 1 year unless an increased risk of bleeding or other contraindications are present. Prasugrel (10 mg/day) is also an option for maintenance therapy, recommended for the same duration. In patients with drug-eluting stents, continuation of thienopyridine therapy for longer than 15 months may be considered (Level of Evidence: C). Other than these recommendations, the guidelines leave the duration of thienopyridine maintenance therapy to the discretion of the clinician. Whether or not a patient should receive treatment beyond 1 year should be based on individual patient factors, such as bleeding risk, age, lesion characteristics, and risk of late stent thrombosis.^1,5

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ACE Inhibitors and ARBs in ACS Patients With Renal Dysfunction
Question: At discharge, should ACE inhibitors and ARBs be withheld in ACS patients with renal dysfunction?

Answer: ACE inhibitors and ARBs offer significant CV and renal benefits in ACS patients, including those with renal dysfunction. The National Kidney Foundation guidelines indicate that ACE inhibitors or ARBs can be used safely in most patients with chronic kidney disease.⁶ Nevertheless, in clinical practice, concerns about these drugs causing hyperkalemia and a decrease in glomerular filtration rate (GFR) often result in clinicians failing to prescribe these recommended maintenance therapies in ACS patients.⁶

When deciding whether to use these medications in ACS patients with renal insufficiency, two factors should be considered: 1) What is the patient's baseline renal function, and 2) Has there been a change in the patient's renal function?

Patients with stable renal insufficiency who are normokalemic can be safely treated with ACE inhibitors or ARBs. Using ACE inhibitors in patients with creatinine levels up to 3.0 mg/dL is considered safe. If the patient has renal dysfunction, initial doses should be low and titrated up slowly; the patient should be monitored closely for the development of hyperkalemia. The National Kidney Foundation guidelines conclude that ACE inhibitors or ARBs can be safely used in patients with renal dysfunction if any decline in GFR over 4 months is less than 30% from baseline value and serum potassium is 5.5 mEq/L or less.⁶

Occasionally, a patient may have an initial increase in creatinine that quickly levels off; this may not be cause for alarm. If creatinine continues to rise, however, ACE inhibitors or ARBs should be discontinued, and the patient should be reevaluated. For instance, determine whether the patient is volume-depleted or has received NSAIDs. Consultation with a nephrologist may be useful. Once renal function restabilizes, the ACE inhibitor or ARB can be initiated again.

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REFERENCES

1. Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention. Circulation. 2009;120(22):2271-2306.

2. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction. J Am Coll Cardiol. 2007;50(7):e1-e157.

3. Mehta SR. A 2x2 factorial randomized trial of optimal clopidogrel and aspirin dosing in patients with non-ST elevation acute coronary syndromes undergoing an early invasive strategy with an intent for PCI: the CURRENT-OASIS-7 trial. Presentation 177. Presented at the European Society of Cardiology Congress, Barcelona, September 2009. http://spo.escardio.org/eslides/view.aspx?eevtid=33&id=177. Accessed July 7, 2010.

4. Petersen JL, Barron JJ, Hammill BG, et al. Clopidogrel use and clinical events after drug-eluting stent implantation: findings from the HealthCore Integrated Research Database. Am Heart J. 2010;159(3):462-470.e1.

5. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. Catheter Cardiovasc Interv. 2007;69(3):334-340.

6. National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Guideline 11: use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in CKD. www.kidney.org/professionals/KDOQI/guidelines_bp/guide_11.htm. Accessed July 7, 2010.

Educational Strategies in Atrial Fibrillation: Improving Guideline-Based Care at the Practice Level Register today for your personalized, certified CME teleconference in atrial fibrillation (AF). This exciting new CME series allows you to discuss guideline- and evidence-based care regarding rate and rhythm control in AF with a faculty expert. For more information, call (toll-free) 866 858 7434 or e-mail concierge@med-iq.com, or you can register today by completing this brief online form.   This activity has been approved for AMA PRA Category 1 Credit™. This activity is supported by an educational grant from sanofi-aventis U.S.

This activity is supported by an educational grant from sanofi-aventis U.S.

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