Practical solutions for implementation of blood cholesterol guidelines in clinical practice.

Underutilization of lipid-lowering therapy (LLT) and failure to attain guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals are important quality gaps in cardiovascular risk optimization, especially among patients with atherosclerotic cardiovascular disease (ASCVD). Large database analyses demonstrate an unmet need for improved LDL-C measurement, and that nearly 75% of patients with ASCVD have an LDL-C level above guideline-recommended levels, and greater than 50% are not treated with statins or ezetimibe. Proposed solutions for overcoming these obstacles to optimal lipid management include provider- and patient-facing educational interventions, health information technology strategies, implementation of incentive-based care, advocacy efforts, and systems-based process innovations. While individual interventions may not be enough to overcome the totality of barriers to optimal LLT, comprehensive multifaceted approaches that address barriers at the provider, patient, and healthcare delivery level are likely to offer the greatest likelihood of success and improved patient outcomes.

Recurrent Atherosclerotic Cardiovascular Disease Events Potentially Prevented with Guideline-Recommended Cholesterol-Lowering Therapy following Myocardial Infarction.

PURPOSE: Many adults with atherosclerotic cardiovascular disease (ASCVD) who are recommended to take a statin, ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) by the 2018 American Heart Association/American College of Cardiology cholesterol guideline do not receive these medications. We estimated the percentage of recurrent ASCVD events potentially prevented with guideline-recommended cholesterol-lowering therapy following a myocardial infarction (MI) hospitalization. METHODS: We conducted simulations using data from US adults with government health insurance through Medicare or commercial health insurance in the MarketScan database. We used data from patients with an MI hospitalization in 2018-2019 to estimate the percentage receiving guideline-recommended therapy. We used data from patients with an MI hospitalization in 2013-2016 to estimate the 3-year cumulative incidence of recurrent ASCVD events (i.e., MI, coronary revascularization or ischemic stroke). The low-density lipoprotein cholesterol (LDL-C) reduction with guideline-recommended therapy was derived from trials of statins, ezetimibe and PCSK9i, and the associated ASCVD risk reduction was estimated from a meta-analysis by the Cholesterol-Lowering Treatment Trialists Collaboration. RESULTS: Among 279,395 patients with an MI hospitalization in 2018-2019 (mean age 75 years, mean LDL-C 92 mg/dL), 27.3% were receiving guideline-recommended cholesterol-lowering therapy. With current cholesterol-lowering therapy use, 25.3% (95%CI: 25.2%-25.4%) of patients had an ASCVD event over 3 years. If all patients were to receive guideline-recommended therapy, 19.8% (95%CI: 19.5%-19.9%) were estimated to have an ASCVD event over 3 years, representing a 21.6% (95%CI: 20.5%-23.6%) relative risk reduction. CONCLUSION: Implementation of guideline-recommended cholesterol-lowering therapy could prevent a substantial percentage of recurrent ASCVD events.

The Projected Impact of Population-Wide Achievement of LDL Cholesterol <70 mg/dL on the Number of Recurrent Events Among US Adults with ASCVD.

PURPOSE: Adults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C <70 mg/dL. METHODS: The number of US adults with ASCVD and LDL-C ≥70 mg/dL was estimated from the National Health and Nutrition Examination Survey 2009-2016 (n = 596). The 10-year cumulative incidence of recurrent ASCVD events was estimated from the REasons for Geographic And Racial Differences in Stroke study (n = 5390), weighted to the US population by age, race, and sex. The ASCVD risk reduction by achieving an LDL-C <70 mg/dL was estimated from meta-analyses of lipid-lowering treatment trials. RESULTS: Overall, 14.7 (95% CI, 13.7-15.8) million US adults had ASCVD, of whom 11.6 (95% CI, 10.6-12.5) million had LDL-C ≥70 mg/dL. The 10-year cumulative incidence of ASCVD events was 24.3% (95% CI, 23.2-25.6%). We projected that 2.823 (95% CI, 2.543-3.091) million ASCVD events would occur over 10 years among US adults with ASCVD and LDL-C ≥70 mg/dL. Overall, 0.634 (95% CI, 0.542-0.737) million ASCVD events could potentially be averted if all US adults with ASCVD achieved and maintained LDL-C <70 mg/dL. CONCLUSION: A substantial number of recurrent ASCVD events could be averted over 10 years if all US adults with ASCVD achieved, and maintained, an LDL-C <70 mg/dL.

Lipid-Lowering Therapy Use and Intensification Among United States Veterans Following Myocardial Infarction or Coronary Revascularization Between 2015 and 2019.

BACKGROUND: Understanding how statins, ezetimibe, and PCSK9i (proprotein convertase subtilisin/kexin type 9 serine protease inhibitors) are prescribed after a myocardial infarction (MI) or elective coronary revascularization may improve lipid-lowering therapy (LLT) intensification and reduce recurrent atherosclerotic cardiovascular disease events. We described the use and intensification of LLT among US veterans who had a MI or elective coronary revascularization between July 24, 2015, and December 9, 2019, within 12 months of hospital discharge. METHODS: LLT intensification was defined as increasing statin dose, or initiating a statin, ezetimibe, or a PCSK9i, overall and among those with an LDL-C (low-density lipoprotein cholesterol) ≥70 or 100 mg/dL. Poisson regression was used to determine patient characteristics associated with a greater likelihood of LLT intensification following hospitalization for MI or elective coronary revascularization. RESULTS: Among 81 372 index events (mean age, 69.0 years, 2.3% female, mean LDL-C 89.6 mg/dL, 33.8% with LDL-C <70 mg/dL), 39.7% were not taking any LLT, and 22.0%, 37.2%, and 0.6% were taking a low-moderate intensity statin, a high-intensity statin, and ezetimibe, respectively, before MI/coronary revascularization during the study period. Within 14 days, 3 months, and 12 months posthospitalization, 33.3%, 41.9%, and 47.3%, respectively, of veterans received LLT intensification. LLT intensification was most common among veterans taking no LLT (82.5%, n=26 637) before MI/coronary revascularization. Higher baseline LDL-C, having a lipid test, and attending a cardiology visit were each associated with a greater likelihood of LLT intensification, while age ≥75 versus <65 years was associated with a lower likelihood of LLT intensification within 12 months posthospitalization. CONCLUSIONS: Less than half of veterans received LLT intensification in the year after MI or coronary revascularization suggesting a missed opportunity to reduce atherosclerotic cardiovascular disease risk.

Lipid Testing Trends Before and After Hospitalization for Myocardial Infarction Among Adults in the United States, 2008-2019.

Background: Routine monitoring of low-density lipoprotein cholesterol (LDL-C) identifies patients who may benefit from modifying lipid-lowering therapies (LLT). However, the extent to which LDL-C testing is occurring in clinical practice is unclear, specifically among patients hospitalized for a myocardial infarction (MI). Methods: Using US commercial claims data, we identified patients with an incident MI hospitalization between 01/01/2008-03/31/2019. LDL-C testing was assessed in the year before admission (pre-MI) and the year after discharge (post-MI). Changes in LDL-C testing were evaluated using a Poisson model fit to pre-MI rates and extrapolated to the post-MI period. We predicted LDL-C testing rates if no MI had occurred (ie, based on pre-MI trends) and estimated rate differences and ratios (contrasting observed vs predicted rates). Results: Overall, 389,367 patients were hospitalized for their first MI during the study period. In the month following discharge, 9% received LDL-C testing, increasing to 27% at 3 months and 52% at 12 months. Mean rates (tests per 1000 patients per month) in the pre- and post-MI periods were 51.9 (95% CI: 51.7, 52.1) and 84.4 (95% CI: 84.1, 84.6), respectively. Over 12 months post-MI, observed rates were higher than predicted rates; the maximum rate difference was 66 tests per 1000 patients in month 2 (rate ratio 2.2), stabilizing at a difference of 15-20 (ratio 1.2-1.3) for months 6-12. Conclusion: Although LDL-C testing increased following MI hospitalization, rates remained lower than recommended by clinical guidelines. This highlights a potential gap in care, where increased LDL-C testing after MI may provide opportunities for LLT modification and decrease risk of subsequent cardiovascular events.

Evaluating a Simple Approach to Identify Adults Meeting the 2018 AHA/ACC Cholesterol Guideline Definition of Very High Risk for Atherosclerotic Cardiovascular Disease.

PURPOSE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline defines very high atherosclerotic cardiovascular disease (ASCVD) risk as a history of ≥ 2 major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. We tested if a simplified approach, having a history of a major ASCVD event, would identify a high proportion of patients that meet the 2018 AHA/ACC cholesterol guideline criteria for very high risk. METHODS: We analyzed data from US adults with health insurance in the MarketScan database who had experienced an acute coronary syndrome in the past year (recent ACS, n = 3626), a myocardial infarction (MI) other than a recent ACS (n = 7572), an ischemic stroke (n = 3551), or symptomatic peripheral artery disease (PAD, n = 5919). Patients were followed from January 1, 2016, through December 31, 2017, for recurrent ASCVD events. RESULTS: Among 16,344 patients with a history of a major ASCVD event, 94.0% met the 2018 AHA/ACC cholesterol guideline definition for very high risk including 92.9%, 96.5%, 93.1%, and 96.2% with a recent ACS, history of MI, history of stroke, and symptomatic PAD, respectively. The incidence of ASCVD events per 1000 person-years was 50.4 (95% CI: 47.6-53.3) among all patients with a history of a major ASCVD event versus 53.1 (95% CI: 50.1-56.1) among patients who met the 2018 AHA/ACC cholesterol guideline definition of very high risk. CONCLUSION: The vast majority of patients with a recent ACS, history of MI, ischemic stroke, or symptomatic PAD meet the 2018 AHA/ACC cholesterol guideline definition of very high risk.

Estimated number and percentage of US adults with atherosclerotic cardiovascular disease recommended add-on lipid-lowering therapy by the 2018 AHA/ACC multi-society cholesterol guideline.

Study objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline recommends a maximally-tolerated statin with add-on lipid-lowering therapy, ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) for adults with very-high atherosclerotic cardiovascular disease (ASCVD) risk to achieve a low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. We estimated the percentage of US adults with ASCVD recommended, by the 2018 AHA/ACC cholesterol guideline, and receiving add-on lipid-lowering therapy. Design setting and participants: Cross-sectional study including 805 participants from the US National Health and Nutrition Examination Survey (NHANES) 2013-2020 data. NHANES sampling weights were used to obtain estimates for the US adult population. Main measures: Very-high ASCVD risk was defined as either: ≥2 ASCVD events, or one ASCVD event with ≥2 high-risk conditions. Being recommended add-on lipid-lowering therapy was defined as having very-high ASCVD risk and LDL-C ≥ 70 mg/dL, or LDL-C < 70 mg/dL while taking ezetimibe or a PCSK9 inhibitor. Results: An estimated 18.7 (95%CI, 16.0-21.4) million US adults had ASCVD, of whom 81.6 % (95%CI, 76.7 %-86.4 %) had very-high ASCVD risk, and 60.1 % (95%CI, 54.5 %-65.7 %) had very-high ASCVD risk and LDL-C ≥ 70 mg/dL. Overall, 61.4 % (95%CI, 55.8 %-66.9 %) were recommended add-on lipid-lowering therapy and 3.2 % (95 % CI, 1.2 %-5.3 %) were taking it. Smokers, adults with diabetes, hypertension and chronic kidney disease were more likely, while those taking atorvastatin or rosuvastatin were less likely, to be recommended add-on lipid-lowering therapy. Conclusion: The majority of US adults with ASCVD are recommended add-on lipid-lowering therapy by the 2018 AHA/ACC cholesterol guideline but few are receiving it.

Low-density lipoprotein cholesterol lowering in real-world patients treated with evolocumab.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited real-world data on LDL-C lowering with evolocumab in United States clinical practice. HYPOTHESIS: We assessed LDL-C lowering during 1 year of evolocumab therapy. METHODS: This retrospective cohort study used linked laboratory (Prognos) and medical claims (IQVIA Dx/LRx and PharMetrics Plus® ) data. Patients with a first fill for evolocumab between 7/1/2015 and 10/31/2019 (index event) and LDL-C ≥ 70 mg/dL were included (overall cohort; N = 5897). Additionally, a patient subgroup with a recent myocardial infarction (MI) within 12 months (median 130 days) before the first evolocumab fill was identified (N = 152). Reduction from baseline LDL-C was calculated based on the lowest LDL-C value recorded during a 12-month follow-up period. RESULTS: The mean (SD) age was 65 (10) years; 61.9% of patients had ASCVD diagnoses and 70.7% of patients were in receipt of lipid-lowering therapy. Following evolocumab treatment, changes in LDL-C from baseline were -60% in the overall cohort (median [interquartile range (IQR)] 146 [115-180] mg/dL to 58 [36-84] mg/dL) and -65% in the recent MI subgroup (median [IQR] 137 [109-165] mg/dL to 48 [30-78] mg/dL). In the overall cohort and recent MI subgroup, 62.1% and 69.7% of patients achieved LDL-C < 70 mg/dL, respectively. CONCLUSIONS: In this real-world analysis, evolocumab was associated with significant reductions in LDL-C comparable to that seen in the FOURIER clinical trial, which were durable over 1 year of treatment.

Ischemic Event Rates in Very-High-Risk Adults.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline includes recommendations for intensive lipid-lowering therapy in patients at very high risk for atherosclerotic cardiovascular disease (ASCVD) events. OBJECTIVES: This study sought to estimate event rates among adults with a history of ASCVD who met and did not meet the definition of very high risk in the 2018 AHA/ACC cholesterol guideline. METHODS: Data from U.S. adults with health insurance in the MarketScan database who had a history of ASCVD on January 1, 2016 (n = 27,775) were analyzed. Very high risk for ASCVD events was defined as a history of ≥2 major ASCVD events or 1 event and ≥2 high-risk conditions. Patients were followed through December 31, 2017, for ASCVD events, including myocardial infarction, ischemic stroke, and major adverse limb events. RESULTS: Overall, 15,366 patients (55.3%) with ASCVD met the definition of very high risk. Among patients with and without very high risk, the ASCVD event rate per 1,000 person-years was 53.1 (95% confidence interval [CI]: 50.1 to 56.1) and 17.0 (95% CI: 15.2 to 18.9), respectively. Among patients with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions, the ASCVD event rate per 1,000 person-years was 89.8 (95% CI: 82.2 to 98.0) and 41.3 (95% CI: 38.3 to 44.4), respectively. The age- and sex-adjusted hazard ratios for ASCVD events among patients with very high risk, overall, with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions versus those without very high risk were 2.98 (95% CI: 2.63 to 3.37), 4.89 (95% CI: 4.22 to 5.66), and 2.33 (95% CI: 2.04 to 2.66), respectively. CONCLUSIONS: The 2018 AHA/ACC cholesterol guideline directs intensive lipid-lowering therapy to adults with a very high ASCVD event rate.