PL Detail-Document #300901 −This PL Detail-Document gives subscribers additional insight related to the Recommendations published in−

PHARMACIST’S LETTER / PRESCRIBER’S LETTER September 2014

Niacin: Who Needs It? Background The primary target of lipid-lowering therapy is LDL because there is a strong relationship between elevated LDL and coronary heart disease.1-3 Moderate doses of statins, which primarily target LDL, decrease cardiovascular morbidity and mortality by 25% to 35% with five years’ use.2,4 Although low HDL and high triglycerides are associated with increased risk for coronary heart disease, evidence of cardiovascular benefit from treating low HDL or high triglycerides is less compelling.1,3,4 For many clinicians, niacin is often the “go-to” add-on when lipid goals are not met with a statin. Furthermore, niacin monotherapy is often used in patients in whom statins have proven intolerable. However, it is unclear if niacin reduces cardiovascular events. This article reviews recent studies of niacin’s effect on cardiovascular outcomes and their implications for patient care.

The AIM-HIGH Study The AIM-HIGH study (Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes) set out to determine if a niacin/statin combination could further reduce the risk of cardiovascular events in patients with cardiovascular disease and well-controlled LDL but low HDL and high triglycerides vs a statin alone.4,5 AIM-HIGH was a multicenter study conducted in over 90 sites in the U.S. and Canada. It was supported by grants from the U.S. Department of Health and Human Services National Institutes of Health (NIH) and Abbott Laboratories. Patients were recruited from internal medicine, cardiology, and diabetes clinics, as well as from cath labs. Included patients were age 45 years and older with coronary artery, cerebrovascular, or peripheral vascular disease. Patients also had to have atherogenic dyslipidemia. For patients not on a statin at entry, this was defined as an LDL of

180 mg/dL (4.7 mmol/L) or less; HDL 40 mg/dL (1 mmol/L) or less for men, or for women HDL 50 mg/dL (1.3 mmol/L) or less; and triglycerides 150 to 400 mg/dL (1.7 to 4.5 mmol/L). For patients on a statin with or without ezetimibe (Zetia [U.S.], Ezetrol [Canada]) at study entry, their measured LDL was adjusted based on the predicted effect of their medication. For men, an HDL of 42 mg/dL (1.1 mmol/L) or less was required, and for women, an HDL of 53 mg/dL (1.4 mmol/L) or less. Triglycerides had to be between 100 mg/dL and 400 mg/dL (1.1 mmol/L to 4.5 mmol/L).4 Exclusion criteria were stroke within eight weeks prior to enrollment, or acute coronary syndrome or planned PCI within four weeks prior to enrollment. CABG within one year prior to enrollment was also an exclusion criterion, except for acute coronary syndrome or angina associated with 50% or greater stenosis. Patients with fasting glucose over 180 mg/dL (10 mmol/L) or A1C over 9% were also excluded. Patients could not have unstable angina, or left main stenosis 50% or greater with no prior CABG. Patients with refractory angina, unresponsive heart failure, or blood pressure over 200/100 mmHg despite treatment were excluded. Other exclusion criteria were cardiogenic shock, ejection fraction less than 30%, pulmonary edema, and valvular disease needing surgery. Patients with a history of revived outpatient sudden death, symptomatic ventricular tachycardia without an ICD, or peptic ulcer disease were also excluded. Transaminases over twice the upper limit of normal, liver disease, recent gout, or SCr 2.5 mg/dL (220 umol/L) or greater were other exclusion criteria. Patients were excluded if they required lipid-lowering therapy other than the study medications, highdose antioxidants, or medications that could increase the risk of myopathy or hepatotoxicity. Pregnancy or possibility of pregnancy, HIV, substance abuse within the past five years, and More. . .

Copyright © 2014 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com

(PL Detail-Document #300901: Page 2 of 5)

comorbidity likely to cause death during followup were other exclusion criteria.4 All patients were given simvastatin 40 mg once daily. After a four- to eight-week run-in to titrate and ensure tolerability of at least 1500 mg daily of niacin, patients were randomized to niacin extended-release (Niaspan) 1500 mg to 2000 mg daily or placebo. The placebo contained immediate-release niacin 50 mg in order to cause flushing to help maintain blinding. During the first year of the study, the simvastatin dose could be adjusted to between 10 mg and 80 mg, and ezetimibe 10 mg could be added to reach the target LDL of 40 to 80 mg/dL (1 to 2.1 mmol/L).4 The primary outcome measure was time from randomization to first CHD death, nonfatal myocardial infarction (MI), ischemic stroke, acute coronary syndrome hospitalization, or symptoms requiring coronary or cerebral revascularization (exclusive of revascularization of restenosis).4 The study was started in September 2005, and enrollment was completed in April 2010.5,6 Almost 3500 patients were randomized.6 Ninetyfour percent of patients were on a statin at enrollment. Of these, at baseline, mean LDL was 71 mg/dL (1.8 mmol/L), mean HDL was 34.9 mg/dL, and mean triglycerides were 161 mg/dL.6 Average age of included patients was 64 years.7 The study was stopped 18 months early because interim analysis showed lack of benefit of simvastatin/niacin vs simvastatin alone.5,7 In addition, there was a small increase in ischemic stroke in the combination group (1.6% vs 0.7%). However, nine of the 28 stroke patients in the combination group had stopped taking their niacin two months to four years prior to the stroke.5 A subsequent safety analysis found that there was also an increase in other serious adverse events in the statin/niacin group compared to placebo (statin-only group). These included serious gastrointestinal side effects (7.4% vs 5.5%, p=0.02) and infections (8.1% vs 5.8%, p=0.008).8

compared to a statin in a secondary prevention population.9 All patients were given simvastatin 40 mg once daily. Ezetimibe 10 mg once daily was added if simvastatin 40 mg was not as effective as their previous therapy, or if their LDL was 135 mg/dL (3.5 mmol/L) or higher after four weeks of simvastatin 40 mg. At the end of this run-in phase, LDL was approximately 63 mg/dL (1.64 mmol/L), and mean HDL was about 44 mg/dL (1.14 mmol/L). Extended-release niacin/laropiprant was then added for eight weeks. Laropiprant is a prostaglandin D2 receptor subtype 1 antagonist that reduces niacinassociated flushing.10,11 Niacin/laropiprant has been marketed as Tredaptive, Cordaptive, and other brand names in about 40 countries, but not the United States or Canada.12 Patients who tolerated niacin/laropiprant were then randomized to continue statin-based therapy plus niacin/laropiprant, or switch to statin-based therapy plus placebo.9 Over 25,000 patients were enrolled. Patients were followed for a median of almost four years. The addition of niacin/laropiprant did not reduce the combined endpoint of coronary death, nonfatal MI, stroke, or need for revascularization vs statin therapy alone. There was also a statistically significant increase in several serious adverse events in patients who received niacin/laropiprant. These included gastrointestinal adverse events such as ulcers, bleeding, dyspepsia, and diarrhea (4.8% vs 3.8%,); skin reactions such as rash (0.7% vs 0.4%); musculoskeletal adverse events, mostly myopathy (3.7% vs 3%); infections (8% vs 6%); and bleeding, including intracranial hemorrhage and GI bleed (2.5% vs 1.9%). In addition, there were 18 more cases of new onset diabetes per 1000 patients, and 37 more cases of worsening of glycemic control per 1000 patients. There was a nonsignificant increase in all-cause mortality in the niacin/laropiprant group vs placebo (6.2% vs 5.7%). Vascular mortality was also increased nonsignificantly.

Meta-Analyses The HPS2-THRIVE Study The HPS2-THRIVE study (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) set out to determine if niacin added to statin-based therapy could further reduce the risk of cardiovascular events

A meta-analysis looked at 11 niacin studies including almost 10,000 patients.13 Most studies were secondary prevention studies. Eight were double-blind. The analysis included the AIMHIGH study, but not HPS2-THRIVE. Use of niacin was associated with a 34% reduction in the composite endpoint of any cardiovascular disease More. . .

Copyright © 2014 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com

(PL Detail-Document #300901: Page 3 of 5)

event (OR 0.66. 95% CI 0.49 to 0.89, p=0.007), and a 25% reduction in major coronary heart disease events (OR 0.75, 95% CI 0.59 to 0.96, p=0.02). Among studies that looked at the effect of a niacin/statin combination, there was a statistically significant reduction in the odds of a cardiovascular event (OR 0.31, 95% CI 0.1 to 0.97, p=0.04). Because HPS2-THRIVE was a negative study and larger than this entire metaanalysis, the results of this analysis may have been different had HPS2-THRIVE been included. Indeed, a more recent meta-analysis that included HPS2-THRIVE found that in patients not receiving a statin, niacin reduced non-fatal MI (OR 0.69, 95% CI 0.56 to 0.85, p=0.0004).14 However, in studies in which patients were taking a statin, there was no benefit on all-cause mortality, MI, coronary death, or stroke.

Commentary Niacin is often added to a statin to raise HDL and further reduce LDL and triglycerides. The results of AIM-HIGH were surprising because niacin was associated with decreased, not increased, stroke risk in the old Coronary Drug Project study.4 But the Coronary Drug Project was a pre-statin study. Most patients in the AIMHIGH and HPS2-THRIVE studies had wellcontrolled LDL on a statin at baseline.6,9 The lack of benefit from adding niacin could have a number of explanations. It may reflect statins’ non-lipid benefits, such as decreased inflammation. Or perhaps cardiovascular risk cannot be reduced beyond the reduction conferred by statins at the lipid levels attained in the study. Another possibility is that baseline HDL may have to be very low to get a benefit from niacin.15 The improvement in HDL provided by niacin may be insufficient to improve cardiovascular event risk.15 Or maybe the study results mean that lowering LDL is more important than raising HDL. Although observational studies show that lifestyle changes (e.g., exercise, smoking cessation, etc) can improve HDL and reduce cardiovascular risk, increasing HDL with medication might not confer the same benefit as lifestyle changes.15 Interestingly, the investigational cholesteryl ester transfer protein inhibitors (e.g., dalcetrapib, torcetrapib) also failed to improve cardiovascular outcomes despite raising HDL.15 One last consideration is that in HPS2-THRIVE there wasn’t a statin plus niacin

alone group, so an antagonistic effect of laropiprant on the cardiovascular benefits of niacin cannot be ruled out.15 In fact, the results of HPS2-THRIVE led to the market withdrawal of all niacin/laropiprant products in Europe on January 21, 2013. It will eventually be withdrawn worldwide.16 However, AIM-HIGH, which did not include laropiprant, did not show a benefit of niacin.5,7 Continue to focus on getting patients with cardiovascular disease on a statin [Evidence level A; high-quality RCTs].17-20 LDL is the primary target.1,3 For more information, see our PL Charts, 2013 ACC/AHA Cholesterol Guidelines (U.S. Subscribers), and Canadian Cardiovascular Society Dyslipidemia Recommendations (Canadian Subscribers). Current evidence suggests that niacin should not be used routinely, especially in patients with diabetes or at risk of diabetes.9,21 For patients who cannot take a statin, consider cholestyramine, colestipol, gemfibrozil, or niacin.4,22-24,27 They have the best outcomes evidence. Fenofibrate has been shown to reduce risk of non-fatal MI and revascularization in patients with diabetes, but did not reduce mortality.25 Ezetimibe lacks outcomes data. In high-risk patients who are taking a statin but not getting the desired LDL-lowering effect (i.e., levels attained in statin outcomes studies), reinforce statin adherence and lifestyle changes, and check for secondary causes.1 Then, consider adding a bile acid sequestrant, ezetimibe, or niacin.1 Fenofibrate can be added to a low- or moderate-intensity statin, but take into account myopathy risk.1 Do not add gemfibrozil due to myopathy risk.1 Keep in mind that there is no evidence of additional cardiovascular benefit from these agents in statin users.1 If the aim is to reduce pancreatitis risk in patients with triglycerides 500 mg/dL (5.7 mmol/L) or higher, consider lifestyle modification, fish oil, fibrates, or niacin.1,21 Canadian guidelines recommend fibrates first-line to prevent pancreatitis in patients with triglycerides >10 mmol/L.28 Re-evaluate risk/benefit of niacin in patients already taking it.26 Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making More. . .

Copyright © 2014 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com

(PL Detail-Document #300901: Page 4 of 5) clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication.

5.

6.

Levels of Evidence In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish. Level A

B

C D

Definition High-quality randomized controlled trial (RCT) High-quality meta-analysis (quantitative systematic review) Nonrandomized clinical trial Nonquantitative systematic review Lower quality RCT Clinical cohort study Case-control study Historical control Epidemiologic study Consensus Expert opinion Anecdotal evidence In vitro or animal study

7.

8. 9.

10.

Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.

11.

Project Leader in preparation of this PL DetailDocument: Melanie Cupp, Pharm.D., BCPS 12.

References 1.

2.

3.

4.

Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1-45. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-39. Anderson TJ, Gregoire J, Hegele RA, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:15167. The AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J 2011;161:47177.

13.

14.

15.

16.

FDA statement on the AIM-HIGH trial. May 26, 2011. http://www.fda.gov/Drugs/DrugSafety/PostmarketD rugSafetyInformationforPatientsandProviders/ucm2 56841.htm. (Accessed August 4, 2014). The AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: impact on Global Health outcomes (AIM-HIGH) trial. Am Heart J 2011;161:538-43. NIH News. NIH stops clinical trial on combination cholesterol treatment. May 26, 2011. http://www.nih.gov/news/health/may2011/nhlbi26.htm. (Accessed August 4, 2014). Anderson TJ, Boden WE, Desvigne-Nickens P, et al. Safety profile of extended-release niacin in the AIM-HIGH Trial. N Engl J Med 2014;371:288-90, HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014;371:203-12. Lai E, DeLepeleire I, Crumley TM, et al. Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1. Clin Pharmacol Ther 2007;81:849-57. Lai E, Wenning LA, Crumley TM, et al. Pharmacokinetics, pharmacodynamics, and safety of a prostaglandin D2 receptor antagonist. Clin Pharmacol Ther 2008;83:840-7. Merck. Press release. Merck announces HPS2THRIVE study of Tredaptive (extended-release niacin/laropiprant) did not achieve primary endpoint. December 20, 2012. http://www.mercknewsroom.com/pressrelease/prescription-medicine-news/merckannounces-hps2-thrive-study-tredaptive-extendedrelea. (Accessed August 4, 2014). Lavigne PM, Karas RH. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J Am Coll Cardiol 2012;61:440-6. Keene D, Price C, Shun-Shin MJ, Francis DP. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117 411 patients. BMJ 2014;349:g4379 doi:10.1136/bmj.g4379. O’Riordan M. HPS-2 THRIVE misses primary end point: no benefit of niacin/laropiprant. December 20, 2012. http://www.theheart.org/article/1490635.do. (Accessed August 4, 2014). Nainggolan L. Niacin/laropiprant products to be withdrawn in EU next week. January 18, 2013. HeartWire. http://www.theheart.org/article/1497081.do. (Accessed August 4, 2014).

More. . . Copyright © 2014 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com

(PL Detail-Document #300901: Page 5 of 5) 17. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005;294:2437-45. 18. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335:1001-9. 19. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-57. 20. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9. 21. Lloyd-Jones DM. Niacin and HDL cholesterol-time to face facts. N Engl J Med 2014;371:271-3. 22. Rifkind BM. Lipid Research Clinics Coronary Primary Prevention Trial: results and implications. Am J Cardiol 1984;54:30C-34C. 23. Watts GF, Lewis B, Brunt JN, et al. Effects on coronary artery disease of lipid-lowering diet, or

24. 25.

26. 27.

28.

diet plus cholestyramine, in the St. Thomas’ Atherosclerosis Regression Study (STARS). Lancet 1992;339:563-9. Insull W Jr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J 2006;99:257-73. Keech A, Simes RJ, Barter P, et al. Effects of longterm fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366:1849-61. HPS2-THRIVE: questions & answers. March 9, 2013. http://www.hps2-thrive.org/qanda_en.pdf. (Accessed August 5, 2014). Robins SJ, Collins D, Wittes JT, et al. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001;285:1585-91. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult-2009 recommendations. Can J Cardiol 2009;25:567-79.

Cite this document as follows: PL Detail-Document, Niacin: Who Needs It?. Pharmacist’s Letter/Prescriber’s Letter. September 2014.

Evidence and Recommendations You Can Trust… 3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright  2014 by Therapeutic Research Center

Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.PharmacistsLetter.com, www.PrescribersLetter.com, or www.PharmacyTechniciansLetter.com

PL Detail-Document #310506 −This PL Detail-Document gives subscribers additional insight related to the Recommendations published in−

PHARMACIST’S LETTER / PRESCRIBER’S LETTER May 2015

Lipid Treatment FAQs The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) lipid guidelines represent a paradigm shift in the treatment of dyslipidemia. The 2015 American Diabetes Association Standards of Medical Care in Diabetes make similar recommendations. The guidelines focus on reducing cardiovascular risk using moderate- or high-intensity statins. (See our PL Chart, 2013 ACC/AHA Cholesterol Guidelines, for a list of high- and moderate-intensity statins.) Familiar tools such as LDL targets, nonstatin lipid medications, and the Framingham risk calculator have fallen by the wayside for the most part. The chart below addresses common questions that arise in practice concerning the new thinking about treatment of lipids. Clinical Question Should I still screen patients for high cholesterol?

Suggested Approach  Assess traditional cardiovascular risk factors (e.g., lipids, blood pressure, diabetes) every four to six years in patients 20 to 79 years of age without atherosclerotic cardiovascular disease.2,6  Patients will be treated based on cardiovascular risk (see next box), not just lipid levels.1

How do I assess cardiovascular risk to help decide if a patient needs a statin for primary prevention?

 For estimation of 10-year cardiovascular disease risk in patients 40 to 75 years of age without cardiovascular disease, not receiving cholesterol-lowering therapy, with LDL 70 to 189 mg/dL, use the Pooled Cohort Equations Cardiovascular Risk Calculator, available at http://my.americanheart.org/cvriskcalculator.1,2  This new calculator was introduced in the 2013 guidelines.  Evidence suggests that predicted risk with the new calculator and observed risk are similar.8  Obtain the patient’s age, sex, race, total and HDL cholesterol, systolic blood pressure, antihypertensive use, presence of diabetes, and smoking status.2  Plug this information into the calculator. The 10-year cardiovascular risk can be used to help you determine whether the patient needs a statin (see first box on next page).  Not all experts agree with its use. For example, the new calculator may overestimate risk in women. 13 See “Can I still use Framingham?” below for information about alternative calculators.

Can I still use Framingham?

 Use the Pooled Cohort Equations Cardiovascular Risk Calculator (the new calculator) for most patients.  The Pooled Cohort Equations Cardiovascular Risk Calculator was developed to be more clinically useful and generalizable than Framingham.3  Framingham was based on data from whites, and was less precise in patients with diabetes. 4 For development of the new calculator, large, diverse, contemporary, community-based, primary prevention cohorts were used.3 Some of the Framingham cohorts were included.3 While Framingham

Continued…

More. . . Copyright © 2015 by Therapeutic Research Center 3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com

(PL Detail-Document #310506: Page 2 of 6)

Clinical Question Can I still use Framingham, continued

Suggested Approach calculated the risk of coronary heart disease, the risk determined with the new calculator is the risk of hard cardiovascular outcomes: coronary death, nonfatal MI, and fatal and nonfatal stroke. 3 These are clinically relevant outcomes.3 Risk estimated with the new calculator does not include risk of coronary heart disease alone, risk of revascularization, or risk of heart failure.3 The new calculator is intended for use in both black and white men and women, with and without diabetes.3  Consider other risk calculators if they were developed in a patient population that more closely matches the patient in question.5 For example, risk in a healthy, non-diabetic female nurse might be best represented by the Reynolds Risk Score.5  See our PL Chart, Common Cardiovascular Risk Calculators, to help you choose the most appropriate calculator for a given patient.

Who do I treat, and how?

 First, determine which of the four “statin benefit groups” the patient fits into. This determines whether the patient should be considered for high- or moderate-intensity statin therapy. The benefit groups and statin dosing are delineated in our PL Chart, 2013 ACC/AHA Cholesterol Guidelines.  Briefly, a statin is recommended for patients with clinical atherosclerotic heart disease, LDL 190 mg/dL or higher, or diabetes and age 40 to 75 years. For other patients age 40 to 75 years with an LDL of 70 to 189 mg/dL, 10-year cardiovascular risk determines if a statin is appropriate. In these patients, a 10-year risk of 7.5% is the point where the benefit of statins appears to exceed the risk.1  Discuss the benefits and risks of statin therapy with the patient BEFORE starting a statin, especially for primary prevention.1  Start with the target dose in most patients; there is no proof that up-titrating improves tolerability.  It is prudent to use cautious dosing in patients more prone to statin side effects: those over 75 years of age, those with a history of statin intolerance, and those taking interacting medications.7

What if a patient doesn’t fit into one of the four benefit groups (see above)?

 If there is clinical suspicion that such a patient may benefit from a statin, additional factors can be taken into consideration.1 These are listed in footnote “a” at the end of the chart. See discussions below on patients 75 years of age.

Should patients 21 to