Quality of Care and Adherence to Statin Therapy in Secondary Prevention Based on the 2013 ACC/AHA Cholesterol Management Guidelines

Statins are a mainstay in both primary and secondary prevention of cardiovascular disease (CVD) and have consistently been shown to decrease cardiovascular morbidity and mortality.1-3 High-dose statin therapy for secondary prevention is a Class IA recommendation by the American College of Cardiology (ACC)/American Heart Association (AHA)4, but despite their proven benefit, there continue to be disparities in prescription patterns as well as adherence to statins in patients with known CVD. For this reason, there is particular interest in identifying gaps in care to better inform means by which to improve statin prescription and adherence.

Patterns of Care

Studies show that, if tolerated, cardiovascular patients benefit more from a high-potency statin at higher doses (i.e., atorvastatin 80 mg or rosuvastatin 20-40 mg).5  When assessing patients hospitalized with an acute myocardial infarction (AMI), the vast majority of patients (87% in one multicenter trial)6 are started on a statin. The main issue appears to be with the dosing and type of statin prescribed. In a study of 4,340 AMIs across 24 U.S. hospitals in 2005-2008, only 26% of patients on sub-optimal statin therapy were changed to a more potent statin or had their statin dose intensified. Only 23% of patients without a contraindication were discharged on maximally potent statin therapy.6 While there was little variation in prescription patterns across enrolled hospitals in the study, there was great variation in the rates of intensification and maximization across hospitals. Interestingly, patients with an ST-segment elevation AMI were approximately 50% more likely to have their statin intensified and maximized than those with a non-ST segment elevation AMI.6 This study suggests that for hospitalized patients, the focus should not be on statin prescription alone but also the dosing and type of statin prescribed. Data from the ACC’s National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) Registry show lower rates of outpatient statin therapy for secondary prevention (68.2%) as compared to inpatient therapy.7,8 There also appears to be significant variation in prescribing patterns between different practices (median rate ratio of 1.31, CI 1.24-1.44), although the reasons for this have yet to be elucidated. These studies imply a disconnect between statin therapy rates in hospitalized patients versus outpatients, possibly due to the greater focus on hospital performance measures. 

There is some suggestion from PINNACLE data that elderly, male, and insured patients are more likely to receive appropriate therapy, although this analysis focused on all recommended secondary prevention medications and not just statins alone.7 Virani et al .recently examined the possible gender disparities in secondary prevention statin therapy using the Department of Veterans Affairs (VA) administrative data.9 They found that women with CVD were indeed less likely to receive a statin (57.6% vs. 64.8% respectively, p <0.0001) or high-intensity statin therapy (21.1% vs. 23.6% respectively, p <0.0001) compared with men, although statin use was low in both genders. There was substantial facility level variation in statin and high-intensity statin use in women. This suggests a gender disparity in statin therapy that correlates with literature acknowledging gender gaps in other areas of cardiovascular care. There appear to be similar racial disparities as well. In a retrospective, single-center analysis of over 3,000 patients hospitalized with known CVD, 62% of black and Hispanic patients were on a statin upon admission as opposed to 72% of white and Asian patients (p <0.0001).10 It should be noted that black and Hispanic patients were less likely to be male, over the age of 65 years, or have health insurance and had significantly more comorbidities, potentially confounding these results. When adjusted for comorbidities, statin prescription did not explain racial and ethnic disparities in one-year mortality and rehospitalization in this study. Therefore, while gender and racial disparities in statin therapy may exist, it is unclear to what extent this affects hard endpoints and certainly requires further investigation.

Statin Adherence

While practice patterns and disparities are known barriers to optimal cardiovascular care, patient adherence to medicines, particularly statins, can be quite challenging. Statin adherence has been reported to be high in large multicenter clinical trials, but substantially lower rates of statin adherence have been reported in registries and cohort studies.11 This may be in large part due to side effects or perceived side effects of these medications. In clinical trials of statins, high-risk patients were often excluded and there were run-in periods in which those with significant side effects were excluded. We, therefore, need a better real-world understanding of the issues surrounding statin adherence. A recent small trial of patients serving as their own control in three double-blind, crossover comparisons (with a three-week washout period in between each phase) showed no statistically significant difference in symptoms during the placebo and statin-therapy periods,12 questioning the true prevalence of statin-induced myopathy. A recent meta-analysis of 14 primary prevention trials also found no significant difference in symptoms between placebo and statin-therapy.13 

Although it is hard to determine true statin intolerance, we do know that certain groups of patients (women, the elderly, the frail, and those with comorbidities) are particularly susceptible to statin side-effects. Thus, they are more likely to be noncompliant. Drug-drug interactions and the number of medications taken also play a large role. High-dose statins can cause greater side effects, and with the new statin guidelines, intolerance and noncompliance may become an increasing issue. In a recent study of 629,005 CVD patients receiving care in the Veterans Health Administration, of which 229,437 (36.5%) received high-intensity statins, there was a statistically significant, albeit modest, reduction in adherence to high-intensity versus low to moderate intensity statins based on calculated proportion of days covered (PDC) [PDC≥0.8, OR 0.94 (CI 0.93-0.96)] for the comparison between high-intensity statin therapy versus low-to-moderate-intensity statin therapy.14 The authors also found that only 36.5% of patients were on a high-dose statin, indicating that a change in practice patterns based on new guidelines may potentially impact patient-reported side effects and adherence. This will, of course, need to be prospectively analyzed given the recent lipid guidelines were just released in 2013. In addition to myalgias and transaminitis, debated diabetes, neuropsychiatric, and renal complications may complicate adherence. Patient education, particularly to dispel popular myths, is a vital part of improving adherence to statins. Intermittent dosing and adjustments to dosing and type of statins, with up-titration if tolerated, may also reduce nonadherence.15

Understanding issues surrounding patterns of care and adherence to statins is vital to improving care. Given large clinical trials showing substantial morbidity and mortality benefit associated with statin therapy in secondary prevention, ensuring that physicians and patients do their part in improving adherence, a so-called “shared accountability,” is integral to providing high-quality care.

References:

  1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
  2. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001;285:1711-8.
  3. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA 1999;282:2340-6.
  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. J Am Coll Cardiol 2014;63:2889-934.
  5. Josan K, Majumdar SR, McAlister FA. The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials. CMAJ 2008;178:576-84.
  6. Arnold SV, Kosiborod M, Tang F, et al. Patterns of statin initiation, intensification, and maximization among patients hospitalized with an acute myocardial infarction. Circulation 2014;129:1303-9.
  7. Maddox TM, Chan PS, Spertus JA, et al. Variations in coronary artery disease secondary prevention prescriptions among outpatient cardiology practices: insights from the NCDR (National Cardiovascular Data Registry). J Am Coll Cardiol 2014;63:539-46.
  8. Arnold SV, Spertus JA, Tang F, et al. Statin use in outpatients with obstructive coronary artery disease. Circulation 2011;124:2405-10.
  9. Virani SS, Woodard LD, Ramsey DJ, et al. Gender Disparities in Evidence-Based Statin Therapy in Patients with Cardiovascular Disease. Am J Cardiol 2015;115:21-6.
  10. Mochari-Greenberger H, Liao M, Mosca L. Racial and ethnic differences in statin prescription and clinical outcomes among hospitalized patients with coronary heart disease. Am J Cardiol 2014;113:413-7.
  11. Kopjar B, Sales AE, Pineros SL, Sun H, Li YF, Hedeen AN. Adherence with statin therapy in secondary prevention of coronary heart disease in veterans administration male population. Am J Cardiol 2003;92:1106-8.
  12. Joy TR, Monjed A, Zou GY, Hegele RA, McDonald CG, Mahon JL. N-of-1 (single-patient) trials for statin-related myalgia. Ann Intern Med 2014;160:301-10.
  13. Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol 2014;21:464-74.
  14. Virani SS, Woodard LD, Akeroyd JM, Ramsey DJ, Ballantyne CM, Petersen LA. Is High-Intensity Statin Therapy Associated With Lower Statin Adherence Compared With Low- to Moderate-Intensity Statin Therapy? Implications of the 2013 American College of Cardiology/American Heart Association Cholesterol Management Guidelines. Clin Cardiol 2014;37:653-9.
  15. Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J 2013;166:597-603.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: American Heart Association, Cholesterol, Comorbidity, Diabetes Mellitus, Drug Interactions, Fluorobenzenes, Heptanoic Acids, Hispanic Americans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Insurance, Health, Myalgia, Myocardial Infarction, Pyrimidines, Pyrroles, Registries, Secondary Prevention, Sulfonamides, Veterans Health


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