Projected Outcomes of Optimized Statin and Ezetimibe Therapy in US Military Veterans with Coronary Artery Disease

Abstract

Importance: Many patients with coronary artery disease (CAD) do not achieve the guideline-directed goals for low-density lipoprotein cholesterol (LDL-C) levels.

Objective: To estimate reductions in the rates of adverse events associated with CAD in a large US military veteran population that may be achieved through use of optimized statin therapy alone or with ezetimibe compared with the prevailing lipid-lowering therapy (LLT).

Design, setting, and participants: In this observational cohort study, US military veterans with CAD were identified by coronary angiography between June 2015 and September 2020 across 82 US Department of Veterans Affairs health care facilities.

Exposures: The exposures were observed LLT, LLT with an optimized statin regimen, and LLT with optimized statin and ezetimibe.

Main outcomes and measures: Observed rates of death, myocardial infarction, stroke, and coronary revascularization, and potential reductions in those outcomes with optimized LLT based on expected further reductions in LDL-C levels and application of formulas from The Cholesterol Treatment Trialists' Collaboration.

Results: The analysis cohort comprised 111 954 veterans (mean [SD] age, 68.4 [8.8] years; 109 390 men [97.7%]; 91 589 White patients [81.8%]; 17 592 Black patients [15.7%]). The median (IQR) observation period for this study was 3.4 (2.1-4.0) years. At the time of index angiography, 66 877 patients (59.7%) were treated with statin therapy, and 623 patients (0.6%) were treated with ezetimibe. At 6 months, the number of patients with statin prescriptions increased to 74 400 (68.7%), but the number of patients with high-intensity statin prescriptions was only 57 297 (52.9%). At 6 months, ezetimibe use remained low (n = 1168 [1.1%]), and LDL-C levels were 70 mg/dL or more in 56 405 patients (52.1%). At 4 years, observed incidences of death, myocardial infarction, stroke, and coronary revascularization were 21.6% (95% CI, 21.3%-21.8%), 5.0% (95% CI, 4.9%-5.2%), 2.2% (95% CI, 2.1%-2.3%), and 15.4% (95% CI, 15.2%-15.7%), respectively. With optimized statin treatment, projected absolute reductions in these incidences were 1.3% (95% CI, 0.9%-1.7%), 0.8% (95% CI, 0.7%-1.0%), 0.2% (95% CI, 0.1%-0.3%), and 2.3% (95% CI, 2.0%-2.7%), respectively. With optimized statin and ezetimibe treatment, projected absolute reductions were 1.8% (95% CI, 1.2%-2.4%), 1.1% (95% CI, 0.9%-1.3%), 0.3% (95% CI, 0.2%-0.4%), and 3.1% (95% CI, 2.6%-3.6%), respectively.

Conclusions and relevance: In this cohort study of veterans with CAD, suboptimal LLT was prevalent in the clinical setting. Optimization of statin therapy was projected to produce clinically relevant reductions in the risks of death and cardiovascular events. Despite a lesser lipid-lowering efficacy of ezetimibe, its widespread use on a population level in conjunction with optimized statin therapy may be associated with further meaningful reductions in cardiovascular risk.

Figure 1.. Prevalence of Lipid-Lowering Therapies During the Study Period

At the time of index coronary angiography, 66 877 patients (59.7%) were prescribed a statin, 39 042 patients (34.9%) were prescribed a high-intensity statin regimen, and ezetimibe use was rare (623 [0.6%]). The proportion of patients prescribed a statin peaked at 3 months following index angiography and then remained generally stable from 6 months through 4 years after index angiography. The use of ezetimibe remained low throughout the study period.

Figure 2.. Observed and Projected Low-Density Lipoprotein Cholesterol (LDL-C) Trajectories

The mean LDL-C levels and 95% CIs for observed lipid-lowering therapy are presented, along with those projected for an optimized statin regimen alone and for an optimized statin regimen with ezetimibe. Compared with observed LDL-C levels, optimized statin treatment was associated with a 21.9 mg/dL (to convert to millimoles per liter, multiply by 0.0259) projected reduction at 1 year and a 23.0 mg/dL projected reduction at 3 years. Compared with optimized statin therapy alone, the addition of ezetimibe was associated with an additional 8.7 mg/dL projected LDL-C value reduction at both 1 and 3 years, corresponding to 30.6 mg/dL and 31.7 mg/dL reductions from observed levels. Thus, the addition of ezetimibe to an optimized statin regimen resulted in a further 39.7% and 37.8% reduction of LDL-C levels of the reductions achieved by optimized statin alone at 1 and 3 years, respectively.

Figure 3.. Projected Absolute Reduction in Cumulative Incidence of Adverse Outcomes with Optimized Lipid-Lowering Therapy (LLT)

The projected percentage of risk reduction is presented for the cumulative incidences of the following 4 subcategories of adverse events: A, death; B, myocardial infarction; C, stroke; and D, coronary revascularization. The error bars represent 95% CIs. The values were projected for optimized statin therapy alone and for optimized statin therapy with ezetimibe.