WHAT IS PEER TO PEER?
Med-IQ's 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 tenth of these e-briefs; in this installment, our expert faculty answer questions about secondary prevention and other considerations for discharge therapy.

Comprehensive risk factor reduction extends survival, decreases the risk of myocardial infarction, and lessens the need for further interventional procedures; therefore, secondary prevention is an integral part of therapy for patients with established coronary artery disease. Although ACC/AHA joint guidelines for the management of UA/NSTEMI provide answers to many questions regarding secondary prevention, approaches to secondary prevention continue to evolve. Below, our faculty explore the role of vitamin D in secondary prevention, tips for maximizing LDL cholesterol reduction, and whether clopidogrel has a role in long-term secondary prevention of ACS.

Determining the Role of Vitamin D in Secondary Prevention
Question:: Is there a role for vitamin D in secondary prevention of ACS?

Answer: There have been many reports regarding the association of vitamin D deficiency and cardiovascular disease (CVD), including coronary heart disease.^1,2 It is not yet known, however, whether supplementation with vitamin D might prove to be an effective primary or secondary prevention strategy for ACS. Other vitamin deficiencies, such as vitamin C and E deficiency, have also been associated with an increased risk of CVD, but multiple trials have shown that supplementation does not reduce CVD risk, and in some instances, such as with vitamin E, supplementation may actually increase the risk of heart failure.³

Hsia and colleagues recently conducted a sub-analysis of the Women's Health Initiative (WHI) randomized trial that compared calcium plus vitamin D supplementation to placebo to assess fracture prevention. They found that supplementation with 400 IU neither increased nor decreased the risk of CVD events. It should be noted, however, that the WHI trial was not specifically designed to assess cardiovascular outcomes; it looked primarily at bone health.⁴ The VITAL trial (Vitamin D and Omega-3), a large NIH-sponsored randomized, controlled trial that is currently under way (www.vitalstudy.org), may provide the answer to whether higher-dose vitamin D supplementation is effective in preventing heart disease. Enrolling 20,000 subjects without known heart disease or cancer, it will examine whether 2,000 IU of vitamin D and/or 1 gm of omega-3 fatty acids can lower the risk of developing heart disease and/or cancer.⁵

Although current guidelines recommend against supplementation with antioxidant vitamins and folic acid because they have not been shown to improve clinical outcomes, there are no guideline recommendations regarding the measurement of vitamin D levels or supplementation with vitamin D in patients with ACS.⁶

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Choosing Effective Strategies to Lower Lipid Levels
Question: Are there any effective strategies to lower lipid levels in ACS patients whose levels remain elevated despite treatment with high-dose statins?

Answer: Rosuvastatin 40 mg is currently the most potent statin available and can be an option for patients whose LDL levels are significantly off-target. Atorvastatin 80 mg is the second most potent statin and has been tested in many large clinical outcomes trials, including the PROVE IT-TIMI 22 trial (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22), which showed benefit over standard statin dosing in patients following ACS.⁷ A recent analysis from the IDEAL trial (Incremental Decrease in End Points Through Aggressive Lipid Lowering), which examined a subgroup of 999 patients who had experienced a recent first myocardial infarction, also found benefit of atorvastatin 80 mg over simvastatin 20 mg to 40 mg.⁸ Using simvastatin 80 mg is another option; however, at this dosage, there is an increased risk of rhabdomyolysis, so monitoring of serum creatinine kinase is essential.⁹ Patients should also not take azole antifungal agents or macrolide antibiotics while on simvastatin 80 mg because of the increased risk of rhabdomyolysis.

The addition of ezetimibe, an intestinal inhibitor of cholesterol absorption, to statin therapy can also be effective in reducing LDL-C levels by approximately an additional 20%.¹⁰ It is not yet known whether ezetimibe actually improves clinical outcomes, although the IMPROVE-IT trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which will be completed in 2013, should address this question.¹¹ ACC/AHA guidelines currently support its use with a statin if needed to control LDL-C levels.¹²

Niacin may also be an effective addition to statin therapy and has been used for decades to treat atherogenic dyslipidemia. It increases HDL-C while decreasing LDL-C and triglycerides.¹³

Finally, if cost is a barrier to providing optimal treatment, it may be reasonable to review the patient's medications and determine whether there are non-essential medications that could be discontinued in favor of treating the dyslipidemia. This is an important point because improving a patient's lipid profile is strongly associated with improved clinical outcomes in ACS, including a substantial decrease in the risk of mortality.⁶

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Assessing Appropriate Use of Clopidogrel as Secondary Prevention
Question: Should I prescribe clopidogrel as secondary prevention for a patient who had an ACS event (treated without stenting) many years ago?

Answer: Current guidelines indicate that clopidogrel should be given for at least one month and up to one year in patients with ACS who have been treated medically or have a bare-metal stent. It may also be given indefinitely in place of aspirin if patients have a contraindication to aspirin therapy.⁶ However, the CHARISMA trial (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) assessed whether the late addition or long-term administration of dual antiplatelet therapy offered any substantial clinical benefit over aspirin alone.¹⁴ Patients with clinically significant CVD or multiple risk factors were assigned to receive clopidogrel and aspirin or aspirin alone, then were followed for 28 months. The primary endpoint was a composite of myocardial infarction, stroke, or death from CVD. The study found no statistically significant differences in outcomes between the two groups, although there was a slight trend toward benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a trend toward negative outcomes in patients with multiple risk factors.¹⁴ Hence, ACC/AHA guidelines do not recommend the long-term use or late addition of clopidogrel in these patients with a history of ACS, except when being used as a substitute for aspirin therapy.⁶ There are no data on the newer P2Y12 inhibitors (prasugrel, which is currently approved for use, or ticagrelor, which is currently under FDA review) for long-term therapy. The use of prasugrel is advocated in the guidelines for the year following percutaneous coronary intervention (PCI) for ACS patients, based on the TRITON-TIMI 38 trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38), where prasugrel treatment was continued for 15 months post-PCI.¹⁵ For ticagrelor, treatment was continued for 12 months following ACS in the PLATO trial (Platelet Inhibition and Patient Outcomes).¹⁶ Thus, no data on the balance of efficacy and safety are currently available for use of these agents in long-term therapy for patients after an ACS event.

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REFERENCES

1. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503-511.

2. Scragg R, Jackson R, Holdaway IM, et al. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol. 1990;19(3):559-563.

3. Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293(11):1338-1347.

4. Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846-854.

5. Largest study of vitamin D and omega-3s set to begin soon at Brigham and Women's Hospital [press release]. Boston, MA: BWH Media Relations; June 23, 2009.

6. 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.

7. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495-1504.

8. Pedersen TR, Cater NB, Faergeman O, et al. Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the incremental decrease in end points through aggressive lipid lowering [IDEAL] trial). Am J Cardiol. 2010;106(3):354-359.

9. Zocor prescribing information. Whitehouse Station, NJ: Merck & Co., Inc. Last updated March 2010.

10. Bruckert E, Giral P, Tellier P. Perspectives in cholesterol-lowering therapy: the role of ezetimibe, a new selective inhibitor of intestinal cholesterol absorption. Circulation. 2003;107;3124-3128.

11. Cannon CP, Giugliano RP, Blazing MA, et al. Rationale and design of IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008;156(5):826-832.

12. King SB 3rd, Smith SC Jr, Hirshfeld JW Jr, et al. 2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention. Circulation. 2008;117(2):261-295.

13. Miller M. Niacin as a component of combination therapy for dyslipidemia. Mayo Clin Proc. 2003;78(6):735-742.

14. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706-1717.

15. Kushner FG, Hand M, Smith SC, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-Elevation myocardial infarction (updating the 2004 guidelines and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update). Circulation. 2009;120:2271-2306.

16. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057.

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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