Cardiovascular (CV) disease (CVD) is the leading cause of death in the United States, with coronary heart disease as the top contributor to this mortality.1 Hyperlipidemia and diabetes mellitus are prevalent within the United States and place individuals at substantial risk for atherosclerotic CVD (ASCVD).1 The primary prevention of ASCVD through the management of blood cholesterol has been emphasized by treatment guidelines over the years.2-4 The optimal management of cholesterol is essential to improving patient care, quality of life, and the burden of CVD.
The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines shifted away from the traditional method of targeting specific lipoprotein levels and instead focused on the benefit of statin therapy in individual patients.3 The patient populations with the highest potential to benefit from primary prevention with statin therapy are people aged ≥21 years with a low-density lipoprotein (LDL) level of ≥190 mg/dL and those aged 40 to 75 years with diabetes and an LDL level between 70 mg/dL and 189 mg/dL.3 Patients with an LDL of ≥190 mg/dL have up to approximately a 5-fold increased risk for ASCVD compared with patients with average (ie, <130 mg/dL) LDL levels, regardless of other risk factors.5 Therefore, the ACC/AHA guidelines recommend high-intensity statin therapy in these patients for the primary prevention of ASCVD.3 Patients with diabetes who can benefit from statin therapy have an increased risk for ASCVD and an increased risk for morbidity and mortality after an ASCVD event.1 Therefore, patients with diabetes who are eligible for primary prevention with statin therapy should receive at least a moderate-intensity or high-intensity statin if their calculated 10-year ASCVD risk is ≥7.5%.3
In late 2018, the ACC/AHA released an update to its 2013 guidelines.4 The statin benefit groups that were studied in this update remained largely the same as in the original guidelines, with the exception of patients with diabetes. Patients within the diabetes benefit group no longer require a 10-year ASCVD risk calculation for escalation to high-intensity statin therapy, and consideration is now given to the general presence of multiple risk factors.4
However, the adoption of evidence-based recommendations by physicians into clinical practice has been estimated to take approximately 17 years.6 Within the first few years after the publication of the 2013 guidelines, only modest changes were seen in the prescribing patterns of statin therapy across the benefit groups.7-9 Barriers to guideline implementation exist on the prescriber level, as well as on the individual patient level.10-13
The patient-related barriers to optimal statin use may include concerns about safety, adverse events, personal preference, lack of understanding or education about the benefits of preventive therapy, or socioeconomic factors.10 However, a recent study showed that more than half of untreated patients who were eligible for statin therapy were never offered a statin by their provider.10
Providers may be unaware of the guideline updates, have preconceived beliefs about the risks and benefits of statin therapy, or prefer conservative approaches to treatment.11-13 Moreover, the guideline update makes implementation even more complicated for prescribers, by replacing a 10-year ASCVD risk calculation with the presence of multiple CV risk factors, without a specific number of risk factors, when determining eligibility for high-intensity therapy in patients with diabetes.4 This guideline change, along with the advent of risk-enhancing factors within the update, provide a significant amount of ambiguity when following recommendations and may potentially create barriers to implementation of the updated guidelines.4
Therefore, although a large body of evidence and guideline recommendations support the use of statin therapy for primary prevention, there is room for improvement. For patients with diabetes, the overall awareness of preventive measures has improved, but there is evidence of significant disparities in the prescription of statin therapy.10,14 Statin therapy is highly underutilized in patients with an LDL of ≥190 mg/dL, despite the known risk for elevated LDL, regardless of other CV risk factors.15-19 Assessing the implementation of the cholesterol guidelines can provide insight on where primary prevention efforts can be improved, on treatment disparity patterns, and on which patient populations require more awareness.
In this retrospective chart review, we evaluated the optimal use of statin therapy in patients seen between January 1, 2015, and November 27, 2018, at the Family Practice Center, a family medicine resident-run clinic associated with East Jefferson General Hospital, a 420-bed nonprofit community hospital in Metairie, LA.
Patients were included based on their eligibility for the primary prevention of ASCVD with statin therapy, based on the benefit group of interest of patients with diabetes, which was defined as an A1c of ≥6.5%, and patients with an LDL level of ≥190 mg/dL. To be included in the diabetes group, patients had to be aged 40 to 75 years and have a diabetes diagnosis and a concurrent LDL level between 70 mg/dL and 189 mg/dL.
Patients within the LDL ≥190 mg/dL group had to be aged ≥21 years and could not have a concurrent diabetes diagnosis. Patients with a diagnosis of clinical ASCVD were excluded, because this population would be eligible for secondary prevention with statin therapy.
Clinical ASCVD was defined as coronary heart disease (history of acute coronary syndrome, myocardial infarction or ischemia, stable or unstable angina, and/or coronary or other arterial revascularization), as well as peripheral arterial disease or stroke (including transient ischemic attack) of presumed atherosclerotic origin. The additional exclusion criteria were pregnancy or breastfeeding, active liver disease, missing or incomplete data, and having a previously established contraindication, intolerance, or allergy to statins.
Comprehensive lists of patients with an LDL ≥190 mg/dL, an A1c ≥6.5%, and an LDL level of 70 to 189 mg/dL were generated using the electronic medical record software at the clinic, resulting in a total of 594 charts obtained. Of these charts, 456 had a recorded A1c of ≥6.5% along with an LDL level of 70 to 189 mg/dL, and 138 charts had a recorded A1c of <6.5% with a recorded LDL level of ≥190 mg/dL (Table 1).
The medical record number, age, race, sex, total cholesterol, LDL, high-density lipoprotein (HDL), systolic blood pressure (BP), diabetes status, hypertension status, and smoking status were collected for each patient. The A1c value was also recorded for patients within the diabetes group. The estimated 10-year ASCVD risk was calculated using the pooled cohort equations recommended by the guidelines.3,4
Data were collected according to the corresponding options on the equation. Race was defined as white, African American, or other. Diabetes status was defined as a documented A1c value of ≥6.5%, or as the presence of a diabetes diagnosis within the medical record. Hypertension status was defined as the presence or absence of concurrent treatment with at least 1 antihypertensive medication. Smoking status was defined as current, former, or never. The presence of a physician-documented ASCVD risk calculation was also collected.
The specific statin, statin dose, and statin intensity were recorded for patients who were initiated with statin therapy and at the last available follow-up appointment. The optimal statin intensity was decided based on guideline recommendations.3 For all patients in the LDL ≥190 mg/dL group, the optimal statin intensity desired was high intensity. For all patients in the diabetes group, the optimal statin intensity desired was at least moderate intensity. The optimal statin intensity desired was high intensity for patients with diabetes and a calculated 10-year ASCVD risk of ≥7.5%.
CV risk factor assessment for each patient was conducted by using the information collected for the ASCVD risk calculation. The presence of a diabetes diagnosis, current or former smoking, and/or the receipt of antihypertensive medication were considered risk factors.3 Traditional risk factors for total cholesterol, HDL, and systolic BP were defined as described by the 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk.20
Accordingly, total cholesterol of ≥180 mg/dL, an HDL of <40 mg/dL for men or <50 mg/dL for women, and/or a systolic BP of ≥140 mm Hg were considered risk factors. The cholesterol treatment guidelines and subsequent update mention LDL of ≥160 mg/dL as a factor to consider when risk assessment is uncertain, and therefore was considered a risk factor.3,4
The risk for clinical ASCVD increases proportionally with age. With the updated recommendations for the consideration of age when screening for risk-enhancing factors, as well as the mention of benefit with high-intensity therapy in patients with diabetes, an age of ≥50 years for men or ≥60 years for women was considered a risk factor.4
The study’s primary outcome was to analyze the mean number of CV risk factors between diabetes and an LDL level of ≥190 mg/dL, which was classified by ASCVD percent risk into the following 4 subgroups: diabetes with an ASCVD risk of ≥7.5%, diabetes with an ASCVD risk of <7.5%, LDL of ≥190 mg/dL with an ASCVD risk of ≥7.5%, and LDL ≥190 mg/dL with an ASCVD risk of <7.5%.
The secondary outcome included the difference between prescribed statin frequency and optimal statin use for the 2 study groups of patients with diabetes or with LDL ≥190 mg/dL. The frequency of statin use, statin intensity, and the correlation between ASCVD risk and the mean number of ASCVD risk factors for the 4 study subgroups were also analyzed as secondary outcomes.
We performed descriptive statistical analysis on this retrospective chart review study. A chi-square test or Fisher’s exact test was used to compare the categorical variables. A paired Student’s t-test and analysis of variance were used to compare the between-group and within-group differences. A correlation analysis was used to compare the ASCVD risk and the number of risk factors for ASCVD. Stata 12 (StataCorp, LLC; College Station, TX) was used to perform statistical analysis, with an alpha level of <.05 considered statistically significant.
The charts of 262 patients were reviewed, with patients meeting inclusion for either the diabetes group or the LDL ≥190 mg/dL group. Table 2 shows the baseline characteristics for the patients in this cohort. The average A1c was 7.95% (standard deviation [SD] ± 1.8). The average systolic BP was similar in both groups, at 131.1 mm Hg (SD ± 18). This is notable, because 72.7% of the patients in the diabetes group were receiving treatment for hypertension compared with only 29.4% in the LDL ≥190 mg/dL group.
The average total cholesterol for all eligible patients was 215.2 mg/dL (SD ± 55.5), with the average being significantly higher in the LDL ≥190 mg/dL group, at 291.3 mg/dL (SD ± 22). A considerable amount (62.2%) of the overall cohort reported never smoking. Of the 262 patients in the study, 171 (65.3%) were prescribed a statin, and only 114 (66.8%) of those eligible patients were prescribed appropriate statin therapy according to guidelines.3,4
The assessment of CV risk factors included the presence of a total cholesterol level of ≥180 mg/dL, an HDL of <40 mg/dL for men or <50 mg/dL for women, systolic BP of ≥140 mm Hg, receiving treatment for hypertension, age ≥50 years for men and ≥60 years for women, LDL of ≥160 mg/dL, and/or smoking status. The highest mean for risk factors was for the patients with diabetes and an ASCVD risk ≥7.5%, at 4.4 (SD ± 1.1; Table 3).
There was a significant difference in the mean number of risk factors between patients with diabetes and an ASCVD risk of <7.5% and patients with diabetes and an ASCVD risk of ≥7.5% (P <.001). Similarly, having an LDL level of ≥190 mg/dL and an ASCVD risk of <7.5% versus having an LDL level of ≥190 mg/dL and an ASCVD risk of ≥7.5% was significant (P <.001).
No significant difference was found in the mean number of risk factors for patients with diabetes and an ASCVD risk of ≥7.5% versus patients with an LDL level of ≥190 mg/dL and an ASCVD risk <7.5% (4.4 [SD ± 1.1] vs 2.9 [SD ± 0.83], respectively; P = .7869). The mean risk factors for patients with diabetes and an ASCVD risk of ≥7.5% versus patients with an LDL level of ≥190 mg/dL and an ASCVD risk of ≥7.5% was also nonsignificant (P = .3271; Table 3).
There was a strong correlation (r = 0.68) between ASCVD risk and the number of risk factors for the total 259 patients included in this analysis (P <.001; Table 4). Furthermore, when separated by their respective group (ie, diabetes or LDL ≥190 mg/dL) and by the ASCVD risk subgroups, a positive correlation was seen with a strong correlation in patients with diabetes and an ASCVD risk of <7.5% and in patients with an LDL level of ≥190 mg/dL and an ASCVD risk of ≥7.5% (Table 4).
There was a significant difference in patients who were prescribed a statin and patients who were not (P = .002), with 70.6% of patients receiving a statin in the diabetes group versus 50% of patients in the elevated LDL group. When evaluating the percentage of patients who were prescribed an optimal statin, there was no difference between the diabetes group and the elevated LDL group (66.4% vs 67.7%, respectively; P = .892).
For patients with diabetes, a significant difference was observed between patients with an ASCVD risk of <7.5% and patients with an ASCVD risk of ≥7.5%, with 59.3% and 75% of patients receiving a statin, respectively (P = .031; Table 5). Among patients with an LDL of ≥190 mg/dL, there was no significant difference between patients receiving a statin with an ASCVD risk of ≥7.5% and those with an ASCVD risk of <7.5%. In addition, no significant difference was seen between patients with diabetes who received a statin and those with an LDL of ≥190 mg/dL at any ASCVD level who received a statin (P >.05). Of the total 171 patients prescribed a statin, there was no significant difference in the intensity level of the statin prescribed (low, moderate, high) between any of the 4 subgroups (P >.05; Table 5).
We performed a retrospective analysis to assess the average number of CV risk factors and how they relate to statin prescribing patterns for patients with an LDL level of ≥190 mg/dL and patients with diabetes, as classified by ASCVD risk. Both of these groups have a substantially increased risk for ASCVD, emphasizing the importance of identifying statin prescribing patterns for the prevention of CV adverse events. These findings provide us with evidence that these groups of patients, although at a high risk for ASCVD adverse events, are not prescribed optimal statin therapy.
The ACC/AHA 2013 guidelines recommended high-intensity statins for patients with diabetes in the age-group of 40 to 75 years if their estimated 10-year ASCVD risk is ≥7.5%.3 However, in 2018, the ACC/AHA no longer recommended calculating a 10-year ASCVD risk for this group, and recommended a high-intensity statin in patients who have contributive risk factors.4 Our study showed that the highest mean risk factor was 4.4 (SD ± 1.1) for diabetes, with a calculated 10-year ASCVD risk of ≥7.5%, which supports the need for high-intensity statin treatment in these patients, based on the 2018 ACC/AHA guidelines.4
In patients with diabetes, those with an ASCVD risk of <7.5% were less likely to receive statin therapy than those in the ASCVD risk ≥7.5% group (59.3% vs 75% of patients, respectively). Although our findings showed no positive correlation for diabetes associated with an ASCVD risk of <7.5% between ASCVD risk and the number of mean risk factors (r = 0.44; P <.001), the 2013 and 2018 ACC/AHA guidelines recommend at least a moderate-intensity statin for these patients.3,4 Furthermore, only 53.3% of those with diabetes and an ASCVD risk of ≥7.5% received a high-intensity statin, yet this group had the highest mean number of risk factors. At the same time, patients with diabetes have a higher risk for ASCVD and have increased risks for morbidity and mortality after an ASCVD event, regardless of the number of risk factors.10
Among the 4 subgroups in our study, patients with diabetes and an ASCVD risk of ≥7.5% had the highest frequency of prescribed statins, whereas the mean risk factors for diabetes and an ASCVD risk of ≥7.5% versus an LDL of ≥190 mg/dL and an ASCVD risk of ≥7.5% were nonsignificant (P = .3271). The similarity in the mean risk factors between the 2 groups supports the recommended higher-intensity statin for these groups, but the prescribing patterns were not similar. The findings in our study related to the prescribing patterns of statins for patients with an LDL of ≥190 mg/dL have been documented in previous studies. Harrison and colleagues conducted a retrospective study in a large integrated health system that aimed to identify trends in statin use before and after the introduction of the 2013 ACC/AHA guidelines.3,21 The investigators found that the patients with LDL of ≥190 mg/dL had significantly lower trends of statin use, at only 45% in 2009 and 44% in 2015 compared with the patients with ASCVD or with diabetes.21
In our study, of patients who were prescribed statins and had an LDL of ≥190 mg/dL and an ASCVD risk of ≥7.5%, 61.1% were prescribed high-intensity statins; however, 42% of the patients in this group never received a statin (Table 5). If patients with an LDL level of ≥190 mg/dL are left untreated, they are at high risk for CV adverse events, even when they are not diagnosed with familial hypercholesterolemia.5 Unlike patients with diabetes, these patients should be evaluated for high-intensity statin therapy, regardless of their ASCVD risk or their number of ASCVD risk factors, which shows a clear disparity that needs to be investigated further and addressed.
One possible explanation for the underuse of statins among patients with diabetes is insufficient clinician guideline observation.22,23 Prescribers may caution away from the use of statins because they are linked to a low risk of slightly increasing A1c levels, even though the CV long-term benefits of statins outweigh these risks.24-26 Suboptimal statin prescribing rates among patients with diabetes are concerning, because statins reduce the risk for CV adverse events by 22% to 37%.27-29 Furthermore, statin therapy use in patients with diabetes reduces CV-related morbidity and mortality, regardless of the LDL levels or a history of CVD.22,28-34 This prescribing statin trend in patients with diabetes may also be observed in the future, with recent US Food and Drug Administration–approved antidiabetic medications, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists, because these treatments have shown some CVD benefits.35
In our study, a lower percentage of patients with an LDL ≥190 mg/dL was prescribed a statin compared with patients with diabetes (irrespective of ASCVD risk). Of patients in the group with an LDL ≥190 mg/dL who did receive a statin, some received a nonoptimal, moderate-intensity statin. A national survey conducted by Virani and colleagues provides a possible explanation for low statin prescription rates, showing that 52% of providers did not follow guidelines when initiating statin therapy in patients with LDL ≥190 mg/dL.16,36 Rather than complying with the standard guidelines, these providers would either continue solely with lifestyle modifications, perform a 10-year ASCVD risk estimation, perform a coronary calcium score, or allow the patient to later follow-up on their lipid levels in 5 years.16
The survey also showed that only 29% of providers knew the difference between low-, moderate-, and high-intensity statin therapies, which indicates that many were not aware that patients with an LDL of ≥190 mg/dL were considered high risk.16,36
The results from this survey propose a possible explanation as to why a health disparity exists in the group of patients with an LDL ≥190 mg/dL and indicates a practice-level variation in care that needs to be addressed. Research shows that for knowledge to be implemented into clinical practice, guideline publication is not enough, and that reinforcement through active engagement with audits and feedback to the providers on their plan of action and care for these patients may be effective.16,36,37
This retrospective study has several limitations. The reasons for this statin prescribing trend might have been influenced by other factors that have not been documented, such as socioeconomic status or insurance status.
Another limitation is the limited number of patients in this retrospective study, and patients with concurrent diabetes and LDL ≥190 mg/dL were excluded, which did not allow for an evaluation of statin prescribing patterns within this high-risk group.
In addition, diabetes-specific risk enhancers discussed in the 2018 cholesterol guidelines were not collected or analyzed.4 Despite these limitations, the study strengths include insight into risk factors for ASCVD and how they correlate with the 10-year ASCVD percent risk.
Our findings show that there is a disparity in the frequency of statin use between patients with an LDL of ≥190 mg/dL and patients with diabetes, putting the former group at a higher risk for ASCVD. Our study also indicates a gap in translating clinical guidelines into clinical practice, which may necessitate the active engagement of prescribers and appropriate feedback. Additional research is warranted to better recognize why a treatment with proven benefits remains inadequately used. In addition, more research is needed to help clinicians identify which risk factors for patients with diabetes specifically, and how many of them, would justify the patients’ qualification for high-intensity statin therapy.
Author Disclosure Statement
Dr Ahmed, Dr Gross, Dr Hammad, Ms Wilson, Dr Nawas, and Dr Zeini have no conflicts of interest to report.
- Benjamin EJ, Muntner P, Alonso A, et al; for the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139:e56-e528. Erratum in: Circulation. 2020;141:e33.
- National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-3421.
- 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(suppl 2):S1-S45. Errata in: Circulation. 2014;129(suppl 2):S46-S48; Circulation. 2015;132:e396.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-e1143. Erratum in: Circulation. 2019;139:e1182-e1186.
- Perak AM, Ning H, de Ferranti SD, et al. Long-term risk of atherosclerotic cardiovascular disease in US adults with the familial hypercholesterolemia phenotype. Circulation. 2016;134:9-19.
- Morris ZS, Wooding S, Grant J. The answer is 17 years, what is the question: understanding time lags in translational research. J R Soc Med. 2011;104:510-520.
- Tran JN, Kao TC, Caglar T, et al. Impact of the 2013 cholesterol guideline on patterns of lipid-lowering treatment in patients with atherosclerotic cardiovascular disease or diabetes after 1 year. J Manag Care Spec Pharm. 2016;22:901-908.
- Olufade T, Zhou S, Anzalone D, et al. Initiation patterns of statins in the 2 years after release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol management guideline in a large US health plan. J Am Heart Assoc. 2017;6:e005205. doi: 10.1161/JAHA.116.005205.
- Pokharel Y, Tang F, Jones PG, et al. Adoption of the 2013 American College of Cardiology/American Heart Association cholesterol management guideline in cardiology practices nationwide. JAMA Cardiol. 2017;2:361-369.
- Bradley CK, Wang TY, Li S, et al. Patient-reported reasons for declining or discontinuing statin therapy: insights from the PALM registry. J Am Heart Assoc. 2019;8:e011765. doi: 10.1161/JAHA.118.011765.
- Virani SS, Pokharel Y, Steinberg L, et al. Provider understanding of the 2013 ACC/AHA cholesterol guideline. J Clin Lipidol. 2016;10:497.e4-504.e4.
- Clough JD, Martin SS, Navar AM, et al. Association of primary care providers’ beliefs of statins for primary prevention and statin prescription. J Am Heart Assoc. 2019;8:e010241. doi: 10.1161/JAHA.118.010241.
- Krempf M, Simpson RJ Jr, Rosen Ramey D, et al. Patient and physician factors influence decision-making in hypercholesterolemia: a questionnaire-based survey. Lipids Health Dis. 2015;14:45. doi: 10.1186/s12944-015-0037-y.
- Gamboa CM, Colantonio LD, Brown TM, et al. Race-sex differences in statin use and low-density lipoprotein cholesterol control among people with diabetes mellitus in the Reasons for Geographic and Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6:e004264. doi: 10.1161/JAHA.116.004264.
- Rodriguez F, Olufade T, Heithoff K, et al. Frequency of high-risk patients not receiving high-potency statin (from a large managed care database). Am J Cardiol. 2015;115:190-195.
- Virani SS, Kennedy KF, Akeroyd JM, et al. Variation in lipid-lowering therapy use in patients with low-density lipoprotein cholesterol ≥190 mg/dL: insights from the National Cardiovascular Data Registry–Practice Innovation and Clinical Excellence registry. Circ Cardiovasc Qual Outcomes. 2018;11:e004652. doi: 10.1161/CIRCOUTCOMES.118.004652.
- Abdullah SM, Defina LF, Leonard D, et al. Long-term association of low-density lipoprotein cholesterol with cardiovascular mortality in individuals at low 10-year risk of atherosclerotic cardiovascular disease: results from the Cooper Center Longitudinal Study. Circulation. 2018;138:2315-2325.
- Fernández-Friera L, Fuster V, López-Melgar B, et al. Normal LDL-cholesterol levels are associated with subclinical atherosclerosis in the absence of risk factors. J Am Coll Cardiol. 2017;70:2979-2991. Erratum in: J Am Coll Cardiol. 2018;71:588-589.
- Navar-Boggan AM, Peterson ED, D’Agostino RB Sr, et al. Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation. 2015;131:451-458.
- Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(suppl 2):S49-S73. Erratum in: Circulation. 2014;129(suppl 2):S74-S75.
- Harrison TN, Scott RD, Cheetham TC, et al. Trends in statin use 2009–2015 in a large integrated health system: pre- and post-2013 ACC/AHA guideline on treatment of blood cholesterol. Cardiovasc Drugs Ther. 2018;32:397-404.
- Mwita JC, Godman B, Esterhuizen TM. Statin prescription among patients with type 2 diabetes in Botswana: findings and implications. BMC Endocr Disord. 2020;20:36. doi: 10.1186/s12902-020-0516-7.
- Elnaem MH, Nik Mohamed MH, Huri HZ, Mohd Shah AS. Effectiveness and prescription pattern of lipid-lowering therapy and its associated factors among patients with type 2 diabetes mellitus in Malaysian primary care settings. Ther Clin Risk Manag. 2019;15:137-145.
- Aiman U, Najmi A, Khan RA. Statin induced diabetes and its clinical implications. J Pharmacol Pharmacother. 2014;5:181-185.
- Ooba N, Tanaka S, Yasukawa Y, et al. Effect of high-potency statins on HbA1c in patients with or without diabetes mellitus. J Pharm Health Care Sci. 2016;2:8. doi: 10.1186/s40780-016-0040-0.
- Pauff BR, Jiroutek MR, Holland MA, Sutton BS. Statin prescribing patterns: an analysis of data from patients with diabetes in the National Hospital Ambulatory Medical Care Survey Outpatient Department and National Ambulatory Medical Care Survey databases, 2005–2010. Clin Ther. 2015;37:1329-1339.
- Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005-2016.
- Colhoun HM, Betteridge DJ, Durrington PN, et al; for the CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): a multicentre randomised placebo-controlled trial. Lancet. 2004;364:685-696.
- Sever PS, Poulter NR, Dahlöf B, et al; for the ASCOT investigators. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial–lipid-lowering arm (ASCOT-LLA). Diabetes Care. 2005;28:1151-1157.
- Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010;376:1670-1681.
- de Vries FM, Denig P, Pouwels KB, et al. Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis. Drugs. 2012;72:2365-2373.
- Hayward RA, Hofer TP, Vijan S. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Intern Med. 2006;145:520-530.
- Perk J, De Backer G, Gohlke H, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33:1635-1701. Erratum in: Eur Heart J. 2012;33:2126.
- Perreault S, Dragomir A, Blais L, et al. Impact of better adherence to statin agents in the primary prevention of coronary artery disease. Eur J Clin Pharmacol. 2009;65:1013-1024.
- American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment. Standards of medical care in diabetes—2018. Diabetes Care. 2018;41(suppl 1):S73-S85.
- Virani SS, Pokharel Y, Steinberg L, et al. Provider understanding of the 2013 ACC/AHA cholesterol guideline. J Clin Lipidol. 2016;10:497-504.
- Institute of Medicine Committee on Quality of Health Care in America. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: National Academy Press; 2001.