What are the most important studies supporting the use of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins?

From the Guidelines

The use of statins is strongly supported by recent and high-quality evidence, particularly the 2017 AHA/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction, which recommends high-intensity statin therapy for patients with clinical atherosclerotic cardiovascular disease, including those with MI 1.

Key Findings

• The Cholesterol Treatment Trialists conducted meta-analyses of individual participant data from randomized trials of more versus less intensive statin regimens, demonstrating a 15% further reduction in major vascular events with more intensive regimens 1.
• The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommends treatment of patients ≤75 years of age who have clinical atherosclerotic cardiovascular disease with high-intensity statin 1.
• The USPSTF found adequate evidence that use of low- to moderate-dose statins reduces the probability of CVD events and mortality by at least a moderate amount in adults aged 40 to 75 years who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10% or greater 1.

Recommendations

• High-intensity statin therapy should be used for patients with clinical atherosclerotic cardiovascular disease, including those with MI, to reduce the risk of recurrent cardiovascular events and mortality 1.
• Moderate-intensity statins are recommended for patients >75 years of age and those who have contraindications/intolerance to high-intensity regimens 1.
• Statin therapy should be individualized in persons >75 years of age according to the potential for ASCVD risk-reduction benefits, adverse effects, drug-drug interactions, and patient preferences 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Importance of Statins in Reducing Cardiovascular Risk

• Statins are the mainstay of therapy for cardiovascular risk reduction in patients with diabetes mellitus, as they reduce the risk of mortality and morbidity mainly by reducing blood low-density cholesterol 2.
• The benefit of statins in patients with coronary heart disease and diabetes is twice as much as compared to the risk in patients with coronary heart disease but no diabetes 2.
• Statins, along with other medical treatments, are responsible for about half of the decrease in cardiovascular mortality over the past several decades 2.

Statins and LDL-Cholesterol Reduction

• Multiple lines of evidence suggest that the physiologically normal levels of low-density lipoprotein cholesterol (LDL-C) and the thresholds for development of atherosclerosis and adverse coronary events are in the 30- to 70-mg/dl range 3.
• Statin therapy with or without ezetimibe, and possibly proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, is used to drive down the LDL-C to a range of about 30 to 50 mg/dl 3.
• Statins reduce LDL-C by about 20% to 45%, while ezetimibe lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy 4.

Combination Therapy with Statins

• Combining statins with ezetimibe or PCSK9 inhibitors, such as evolocumab, can improve the lipid-lowering effect and reduce the risk of cardiovascular events 5, 4.
• The combination of statins, ezetimibe, and evolocumab may be an effective strategy for lowering cholesterol and reducing the risk of coronary heart disease 4.
• Future strategies in population risk reduction in diabetics should include maximal statin therapy, additional treatment with non-statin therapy, and new paradigms of prevention with early intervention with shorter, more intensive therapy to potentially "reverse" atherosclerosis 2.

Safety and Efficacy of Statins

• Statins are generally safe and well-tolerated, with no increased risk of serious adverse events, myalgias, or liver-related harms 6.
• The benefits of statin therapy appear consistent in demographic and clinical subgroups, including populations without marked hyperlipidemia 6.
• Statin therapy is associated with reduced risk of all-cause and cardiovascular mortality and CVD events, with greater absolute benefits in patients at greater baseline risk 6.