Statins for the primary prevention of cardiovascular disease

Use of HMG-CoA reductase inhibitors (i.e., statins) for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) can be an ambiguous and somewhat contentious therapeutic issue due to the number of, and complexity and variation in, guideline recommendations. The goal of this column is to provide some clarity and insight regarding how to approach using statins for primary prevention. Primary vs. secondary prevention To begin, it is crucial to define what is meant by primary versus secondary cardiovascular prevention. Primary prevention simply refers to patients without any evidence or history of ASCVD, whereas secondary prevention relates to patients who have some manifestation of ASCVD, such as a myocardial infarction, stable or unstable angina, stroke, transient ischemic attack or peripheral artery disease. General consensus among guidelines is that statin therapy should be recommended for all patients with a history of ASCVD, typically at a high dose (e.g., atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily).1-3 Recent guideline recommendations for primary prevention The 2021 Canadian Cardiovascular Society (CCS) dyslipidemia guidelines recommend statin therapy for certain higher-risk primary prevention patients (i.e., those with a “statin-indicated condition”).1 These include select patients with diabetes mellitus, chronic kidney disease or a genetic dyslipidemia (low-density lipoprotein cholesterol [LDL-C] ≥ 5 mmol/L). In patients without ASCVD or a statin-indicated condition, the decision to start statin therapy is based on an objective assessment of the patient’s 10-year cardiovascular risk (e.g., using the Framingham Risk Score). The CCS guidelines generally do not recommend statins in patients with a 10-year cardiovascular risk score of 0 or family history of premature ASCVD. Patients with a risk score of 10%–19.9% are recommended to receive a statin if they have an LDL-C ≥ 3.5 mmol/L or meet other criteria (e.g., men aged ≥ 50 years or women aged ≥ 60 years with ≥ 1 cardiovascular risk factor, such as hypertension or smoking). Patients with a risk score of ≥ 20% are also recommended to receive statin therapy. However, it is important to note these thresholds are arbitrary and ultimately the decision to start therapy should be based on the patient’s values and preferences. In 2022, the United States Preventive Services Task Force (USPSTF) published new recommendations for the use of statins in patients without a history of ASCVD.4 The USPSTF distilled the evidence into three basic recommendations based on moderate-certainty evidence. First, statin therapy is recommended for persons aged 40–75 years who have one or more ASCVD risk factors, such as dyslipidemia, diabetes, hypertension or smoking, and a 10-year cardiovascular risk of ≥10%. The task force advocates using the American College of Cardiology/American Heart Association Pooled Cohort Equations calculator (https://tools.acc.org/ASCVD-Risk-Estimator-Plus) to assess patients’ 10-year cardiovascular risk. However, given its familiarity among clinicians, the Framingham Risk Score is also likely a reasonable option. Second, the task force recommended that “clinicians selectively offer a statin” for patients aged 40–75 years who have one or more ASCVD risk factors and a 10-year cardiovascular risk of 7.5%–9.9%, noting that “the likelihood of benefit is smaller in this group than in persons with a 10-year risk of 10% or greater.” Finally, the task force concluded that there is insufficient evidence to assess the benefits and risks of initiating statin therapy for primary prevention in patients aged > 75 years. They do not, however, provide guidance about whether or not statin therapy should be continued in patients ≥ 76 years of age if they were started on a statin earlier in life. Of note, these recommendations are not applicable to patients with an LDL-C of > 4.9 mmol/L or known familial hypercholesterolemia.4 Dosing Most primary prevention statin trials used a fixed, moderate-intensity dose.5,6 Atorvastatin 10–20 mg or rosuvastatin 5–10 mg daily (dubbed the “fire and forget” approach) is a reasonable option for most patients. The CCS guidelines recommend escalating a patient’s statin dose if their lipid values remain above a certain threshold (e.g., LDL-C ≥ 2.0 mmol/L), and considering the addition of another lipid-lowering drug (e.g., ezetimibe, bile acid sequestrant) if their lipids remain above threshold despite maximally tolerated statin dose,1 yet the evidence to support this approach is weak. The USPSTF does not advocate for a specific lipid target or threshold, but rather states that “use of moderate-intensity statin therapy seems reasonable for the primary prevention of CVD in most persons.”4 Summary Both the CCS and USPSTF guidelines generally recommend statin therapy for primary prevention in persons aged 40–75 years with a 10-year cardiovascular risk of ≥ 10% and ≥ 1 cardiovascular risk factor. This population should be the focus of efforts to initiate and optimize statin therapy. Pharmacists can play a vital role in identifying patients who meet these criteria, and discussing the benefits and risks of statin therapy. Arden Barry, BSc, BSc(Pharm), PharmD, ACPR is a clinical pharmacy and research specialist in ambulatory cardiology at the Jim Pattison Outpatient Care and Surgery Centre in Surrey, BC, and associate professor (partner) at the Faculty of Pharmaceutical Sciences, University of British Columbia in Vancouver, BC. References: Pearson GJ, Thanassoulis G, Anderson TJ, et al. 2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults. Can J Cardiol 2021;37:1129-50. 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. J Am Coll Cardiol 2019;73:e285-e350. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88. US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA 2022;328:746-53. Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ 2009;338:b2376. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2021-31.

Statins for the primary prevention of cardiovascular disease

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