Portal de Periódicos da CAPES

Usefulness of Statins as Secondary Prevention Against Recurrent and Terminal Major Adverse Cardiovascular Events

2022; Elsevier BV; Volume: 176; Linguagem: Inglês

10.1016/j.amjcard.2022.04.018

1879-1913

Kristen M. Tecson, Aaron Y. Kluger, Andrea E. Cassidy‐Bushrow, Bin Liu, Chad M. Coleman, Laney K. Jones, Celeena Jefferson, Jeffrey J. VanWormer, Peter A. McCullough,

Pharmaceutical Economics and Policy

Clinical guidelines recommend statins for patients with atherosclerotic cardiovascular disease (ASCVD), but many remain untreated. The goal of this study was to assess the impact of statin use on recurrent major adverse cardiovascular events (MACE). This study used medical records and insurance claims from 4 health care systems in the United States. Eligible adults who survived an ASCVD hospitalization from September 2013 to September 2014 were followed for 1 year. A multivariable extended Cox model examined the outcome of time-to-first MACE, then a multivariable joint marginal model investigated the association between post-index statin use and nonfatal and fatal MACE. There were 8,168 subjects in this study; 3,866 filled a statin prescription ≤90 days before the index ASCVD event (47.33%) and 4,152 filled a statin prescription after the index ASCVD event (50.83%). These post-index statin users were younger, with more co-morbidities. There were 763 events (315/763, 41.3% terminal) experienced by 686 (8.4%) patients. The adjusted overall MACE risk reduction was 18% (HR 0.82, 95% CI 0.70 to 0.95, p = 0.007) and was more substantial in the first 180 days (HR 0.72, 95% CI 0.60 to 0.86, p <0.001). There was a nonsignificant 19% reduction in the number of nonfatal MACE (rate ratio 0.81, 95% CI 0.49 to 1.32, p = 0.394) and a 65% reduction in the risk of all-cause death (HR 0.35, 95% CI 0.22 to 0.56, p <0.001). In conclusion, we found a modest increase in statin use after an ASCVD event, with nearly half of the patients untreated. The primary benefit of statin use was protection against early death. Statin use had the greatest impact in the first 6 months after an ASCVD event; therefore, it is crucial for patients to quickly adhere to this therapy. Clinical guidelines recommend statins for patients with atherosclerotic cardiovascular disease (ASCVD), but many remain untreated. The goal of this study was to assess the impact of statin use on recurrent major adverse cardiovascular events (MACE). This study used medical records and insurance claims from 4 health care systems in the United States. Eligible adults who survived an ASCVD hospitalization from September 2013 to September 2014 were followed for 1 year. A multivariable extended Cox model examined the outcome of time-to-first MACE, then a multivariable joint marginal model investigated the association between post-index statin use and nonfatal and fatal MACE. There were 8,168 subjects in this study; 3,866 filled a statin prescription ≤90 days before the index ASCVD event (47.33%) and 4,152 filled a statin prescription after the index ASCVD event (50.83%). These post-index statin users were younger, with more co-morbidities. There were 763 events (315/763, 41.3% terminal) experienced by 686 (8.4%) patients. The adjusted overall MACE risk reduction was 18% (HR 0.82, 95% CI 0.70 to 0.95, p = 0.007) and was more substantial in the first 180 days (HR 0.72, 95% CI 0.60 to 0.86, p <0.001). There was a nonsignificant 19% reduction in the number of nonfatal MACE (rate ratio 0.81, 95% CI 0.49 to 1.32, p = 0.394) and a 65% reduction in the risk of all-cause death (HR 0.35, 95% CI 0.22 to 0.56, p <0.001). In conclusion, we found a modest increase in statin use after an ASCVD event, with nearly half of the patients untreated. The primary benefit of statin use was protection against early death. Statin use had the greatest impact in the first 6 months after an ASCVD event; therefore, it is crucial for patients to quickly adhere to this therapy. IntroductionMillions of adults in the United States (US) are affected by cardiovascular events each year, reducing their quality of life and increasing their risk for death.1Pahwa R Jialal I Atherosclerosis.StatPearls. 2021; Google Scholar Hyperlipidemia is a significant risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), which is present in 47% of young adults with ASCVD.2Virani SS Alonso A Benjamin EJ Bittencourt MS Callaway CW Carson AP Chamberlain AM Chang AR Cheng S Delling FN Djousse L Elkind MSV Ferguson JF Fornage M Khan SS Kissela BM Knutson KL Kwan TW Lackland DT Lewis TT Lichtman JH Longenecker CT Loop MS Lutsey PL Martin SS Matsushita K Moran AE Mussolino ME Perak AM Rosamond WD Roth GA Sampson UKA Satou GM Schroeder EB Shah SH Shay CM Spartano NL Stokes A Tirschwell DL VanWagner LB Tsao CW American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2020 update: a report from the.American Heart Association. Circulation. 2020; 141: e139-e596Google Scholar,3Vikulova DN Grubisic M Zhao Y Lynch K Humphries KH Pimstone SN Brunham LR. Premature atherosclerotic cardiovascular disease: trends in incidence, risk factors, and sex-related differences, 2000 to 2016.J Am Heart Assoc. 2019; 8e012178Crossref PubMed Scopus (43) Google Scholar Lipid-lowering therapy is a cornerstone of secondary ASCVD prevention, but many patients remain untreated. The near-term consequences of medication underutilization after an acute event are not well understood. Although there is a panoply of lipid-lowering therapies, we chose to limit this analysis to the American Heart Association guideline-recommended first-line medication of statins.4Arnett DK Blumenthal RS Albert MA Buroker AB Goldberger ZD Hahn EJ Himmelfarb CD Khera A Lloyd-Jones D McEvoy JW Michos ED Miedema MD Muñoz D Smith SC Virani SS Williams KA Yeboah J Ziaeian B. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Circulation. 2019; 140: e596-e646PubMed Google Scholar Hence, the purpose of this report is to study the association between statin use/nonuse and recurrent major adverse cardiovascular events (MACE) in a cohort of patients across the US who had a recent acute ASCVD event.MethodsThis study is a collaboration between 4 US health care systems (Baylor Scott & White [BSW], Texas; Henry Ford, Michigan; Geisinger, Pennsylvania; and Marshfield Clinic, Wisconsin) participating in the Health Care Systems Research Network (HCSRN). The HCSRN maintains data standards between health care organizations to create a common data model to assemble pooled data sets to answer multicenter research questions.5Health Care Systems Research Network. Mission and vision. Available at: http://www.hcsrn.org/en/About/. Accessed June 29, 2021.Google Scholar For this project, BSW developed and distributed code to collaborators to extract the minimum necessary care, administrative, and claims data to yield a deidentified dataset. This study received approval from the Baylor Scott & White Research Institute's institutional review board through expedited review and a waiver of informed consent. Henry Ford and Marshfield ceded to the Baylor Scott & White Research Institute's institutional review board with a reliance agreement, and Geisinger's institutional review board determined that the study did not involve human subjects and was not subject to their oversight.We used a retrospective cohort design to answer our research question. Eligible adults survived an index ASCVD hospitalization from September 30, 2013 to September 30, 2014 and were followed up to 1 year. We extracted demographics (gender, age, race, Hispanic ethnicity, and insurance type), and used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and prescription fills during the year prior to the index to identify co-morbidities (type II diabetes mellitus, chronic kidney disease, hyperlipidemia, and hypertension). We recorded statin use 90 days before and after the index. The primary outcome was MACE (acute myocardial infarction, ischemic stroke, revascularization, unstable angina, acute presentation of chronic ASCVD, all-cause death) within 1 year of index.We created a multivariable extended Cox model with robust sandwich estimates to investigate the association between post-index statin use (assessed through prescription fill) and time-to-first recurrent MACE while accounting for clustering (by healthcare system), demographics (gender, age, race), and co-morbidities (type II diabetes mellitus, chronic kidney disease, hyperlipidemia, hypertension, ASCVD history). After analyzing the time-to-first MACE, we considered an alternate analytic framework using the marginal joint model of Huang and Wang6Huang CY Wang MC. Joint modeling and estimation for recurrent event processes and failure time data.J Am Stat Assoc. 2004; 99: 1153-1165Crossref PubMed Scopus (154) Google Scholar to make inferences using the comprehensive profile of recurrent and terminal events.7Charles-Nelson A Katsahian S Schramm C. How to analyze and interpret recurrent events data in the presence of a terminal event: an application on readmission after colorectal cancer surgery.Stat Med. 2019; 38: 3476-3502PubMed Google Scholar This model implies that the subject-specific event rate is positively correlated with the risk of terminal event (i.e., subjects who survive longer tend to have lower event rates); although, this model has also been shown to yield unbiased estimates for independent processes.7Charles-Nelson A Katsahian S Schramm C. How to analyze and interpret recurrent events data in the presence of a terminal event: an application on readmission after colorectal cancer surgery.Stat Med. 2019; 38: 3476-3502PubMed Google Scholar Herein, we distinguished MACE as being nonfatal (recurrent) or fatal (terminal). Because the model could not provide stable estimates for the third or fourth events owing to the small event counts, we included information only through the second MACE. We used the same covariates as the first model but dichotomized age and race to improve computational efficiency. We used a nonparametric bootstrap method for clustered data by repeatedly sampling the subjects with replacement to estimate standard errors and obtain 95% confidence intervals (CIs) and p-values. Analyses were performed in SAS version 9.4 (Cary, North Carolina) and the 'reReg' R package.8Chiou SH, Huang CY. Recurrent event regression. CRAN. Available at: https://cran.r-project.org/web/packages/reReg/reReg.pdf. Accessed March 8, 2021.Google ScholarResultsThere were 8,168 patients in this study, with the 3 leading causes of entry being acute presentation of chronic ASCVD (2,337, 28.6%), acute myocardial infarction (2,156, 25.4%), and ischemic stroke (1,458, 17.9%). There were 3,866 patients (47.33%) who filled a statin prescription in the 90 days before the index event; statin users increased to 4,152 within 90 days after index (50.83%). These post-index statin users were younger with more co-morbidities than nonusers (Table 1). Of the pre-index statin users, 3,274 continued treatment after the index event (84.69%); 878 of pre-index nonusers (20.41%) were initiated on statins after index. There were 763 events experienced by 686 patients (8.4%) within 1 year (Table 2). Of all events, 315 were terminal (41.3%); most deaths (284, 90.2%) occurred as the first MACE in follow-up.Table 1Patient characteristics of statin users and non-usersStatin use after index eventCharacteristicYes (n = 4,152)No (n = 4,016)P-valueMale2,346 (56.5%)2,176 (54.18%)0.0350Age (years)72.3 [62.2, 81.0]75.2 [65.9, 83.5]<0.0001Age category (years)<0.0001 18–348 (0.19%)62 (1.54%) 35–4485 (2.05%)72 (1.79%) 45–54334 (8.04%)250 (6.23%) 55–64835 (20.11%)555 (13.82%) 65–741,115 (26.85%)1,015 (25.27%) 75+1,775 (42.75%)2,062 (51.34%)Race0.0032 Black378 (9.1%)406 (10.11%) White3,287 (79.17%)3,056 (76.1%) Other/unknown487 (11.73%)554 (13.79%)Hispanic0.0003 Yes80 (1.93%)52 (1.29%) No3,619 (87.16%)3,425 (85.28%) Unknown453 (10.91%)539 (13.42%)Insurance<0.0001 Commercial1,644 (39.60%)1,295 (32.25%) Medicaid213 (5.13%)181 (4.51%) Medicare2,241 (53.97%)2,383 (59.34%) Other payors†Includes health maintenance organizations, indemnity plans, patient-funded, and unknown/missing insurance data. ASCVD = atherosclerotic cardiovascular disease.54 (1.30%)157 (3.91%)Current smoker645 (15.53%)604 (15.04%)0.5345Type I diabetes mellitus424 (10.21%)336 (8.37%)0.0041Type II diabetes mellitus1,902 (45.81%)1,615 (40.21%)<0.0001Chronic kidney disease1,108 (26.69%)1,142 (28.44%)0.0767Hyperlipidemia3,496 (84.2%)3,020 (75.2%)<0.0001Hypertension3,624 (87.28%)3,402 (84.71%)0.0008Index event<0.0001 Acute myocardial infarction1,143 (27.53%)1,013 (25.22%) Angina pectoris60 (1.45%)93 (2.32%) Ischemic stroke or transient ischemic attack736 (17.73%)859 (21.39%) Peripheral arterial disease445 (10.72%)592 (14.74%) Revascularization547 (13.17%)343 (8.54%) Other1,221 (29.41%)1,116 (27.79%)History of ASCVD (in year prior to index)602 (14.5%)563 (14.02%)0.5350† Includes health maintenance organizations, indemnity plans, patient-funded, and unknown/missing insurance data.ASCVD = atherosclerotic cardiovascular disease. Open table in a new tab Table 2Description of all major adverse cardiac eventsMajor Adverse Cardiac Event Within 1 y of IndexEvent TypeFirstSecondThirdFourthTotalAcute myocardial infarction141 (20.6%)12 (16.7%)1 (25.0%)0154 (20.2%)Angina pectoris63 (9.2%)9 (12.5%)1 (25.0%)073 (9.6%)Ischemic stroke66 (9.6%)7 (9.7%)0073 (9.6%)Revascularization132 (19.2%)15 (20.8%)01 (100%)148 (19.4%)Death284 (41.4%)29 (40.3%)2 (50.0%)0315 (41.3%)Total Events6867241763 Open table in a new tab The unadjusted effect of post-index statin use was associated with a 20% reduction in the risk of 1-year MACE (HR: 0.80, 95% CI: 0.69 to 0.93, p = 0.0043) and was similar after adjusting for demographics and co-morbidities (adjusted HR: 0.82, 95% CI: 0.70 to 0.95, p = 0.0074). We observed a time-dependent effect of statin use (interaction term between time and statin use: p 180 days. This unadjusted model showed a 29% risk reduction (HR: 0.71, 95% CI: 0.59 to 0.85, p = 0.0003) in the initial 180 days after the index for those who used a statin versus those who did not. However, it was not associated with the MACE outcome after 180 days (HR: 1.04, 95% CI: 0.80 to 1.35, p = 0.7663). Similarly, the adjusted model showed a 28% risk reduction (HR: 0.72, 95% CI: 0.60 to 0.86, p = 0.0004) in the initial 180 days after the index event for those who used a statin compared with those who did not (Figure 1). All-cause death was a substantial driver of the MACE risk difference, with 93 post-index statin users (2.24%) dying versus 191 nonusers (4.76%).In the alternate analytic framework, which distinguished MACE as nonfatal (recurrent) and terminal, we found that taking a statin after index was associated with a (nonsignificant) 20% reduction in the number of nonfatal MACE recurrences (rate ratio = 0.80, 95% CI 0.46 to 1.39, p = 0.429) and a 67% reduction in the risk of all-cause death (HR 0.33, 95% CI 0.23 to 0.49, p <0.001). The effect of taking a statin was similar after adjusting for demographics and co-morbidities (Table 3). From this multivariable joint model, we found that taking a statin was associated with a (nonsignificant) 19% reduction in the number of nonfatal MACE recurrences (rate ratio = 0.81, 95% CI 0.49 to 1.32, p = 0.394) as well as a 65% reduction in the risk of all-cause death (HR 0.35, 95% CI 0.22 to 0.56, p 73.79 years) more than doubled the risk of all-cause death and being White was associated with more than a 2-fold increase in risk of recurrent (nonfatal) MACE. Figure 2 depicts the patients under observation and their MACE according to statin use.Table 3Results from the joint marginal model for recurrent and terminal major adverse cardiovascular eventsRecurrent Event ProcessTerminal Event ProcessVariableRate Ratio95% CIP-valueHazard Ratio95% CIP-valueStatin use post-index (yes vs. no)0.810.49–1.320.3940.350.22–0.56<0.001Gender (female vs. male)1.000.59–1.680.9940.940.58–1.520.794Caucasian (yes vs. no)2.451.50–4.01<0.0011.090.54–2.220.811Type II Diabetes Mellitus (yes vs. no)1.400.88–2.210.1500.960.58–1.610.889Chronic Kidney Disease (yes vs. no)1.060.67–1.690.7970.940.57–1.560.816Hyperlipidemia (yes vs. no)0.920.52–1.630.7680.650.32–1.340.245Hypertension (yes vs. no)0.710.26–1.910.4981.120.34–3.730.852Age (above vs. below median)1.520.87–2.660.1452.561.52–4.29 3) were more likely to adhere to a statin regimen.11Ahmed ST Mahtta D Rehman H Akeroyd J Al Rifai M Rodriguez F Jneid H Nasir K Samad Z Alam M Petersen LA Virani SS Association between frequency of primary care provider visits and evidence-based statin prescribing and statin adherence: findings from the Veterans Affairs system.Am Heart J. 2020; 221: 9-18Crossref PubMed Scopus (6) Google ScholarBecause nonadherence to statins is a widespread problem, many have researched interventions to improve it. Elkomos and coworkers15Elkomos M Jahromi R Kelly MS. Pharmacist-led programs to increase statin prescribing: a narrative review of the literature.Pharmacy (Basel). 2022; 10: 13Crossref PubMed Google Scholar found that several types of pharmacist-led interventions improved statin adherence, with the most successful type of intervention being between pharmacists and providers. In one such intervention, pharmacists contacted physicians of patients recently admitted for coronary heart disease, and the rates of statin use were 72% for patients in the intervention group versus 43% for patients in the control group at 2 years. Similarly, George and coworkers20George NE Shukkoor AA Joseph N Palanimuthu R Kaliappan T Gopalan R. Implementation of clinical audit to improve adherence to guideline-recommended therapy in acute coronary syndrome.Egypt Heart J. 2022; 74: 4Crossref PubMed Scopus (2) Google Scholar found that adherence to guideline-directed medical therapy improved when clinical pharmacists performed periodic clinical audits and sent reports to cardiologists. Rana and coworkers21Rana JS Virani SS Moffet HH Liu JY Coghlan LA Vasadia J Ballantyne CM Karter AJ. Association of low-density lipoprotein testing after an atherosclerotic cardiovascular event with subsequent statin adherence and intensification.Am J Med. 2021; (S0002–9343(21):00794–00794)Google Scholar found that patients who had been hospitalized for ASCVD were more likely to adhere to statins if they had LDL-C testing after discharge. Lansberg et al22Lansberg P Lee A Lee ZV Subramaniam K Setia S. Nonadherence to statins: individualized intervention strategies outside the pill box.Vasc Health Risk Manag. 2018; 14: 91-102Crossref PubMed Scopus (26) Google Scholar suggest that collaboration between physicians and pharmacists is needed to produce patient-directed interventions including counseling, education, removing barriers to care, and medication reminders. Yao et al23Yao S Lix L Teare G Evans C Blackburn D. The impact of age and sex concordance between patients and physicians on medication adherence: a population-based study.Patient Prefer Adherence. 2022; 16: 169-178Crossref PubMed Scopus (2) Google Scholar even detected a better statin adherence rate for patients who were the same gender as their prescribing physician. Taken together, it is clear that combating the problem of nonadherence requires an investment of time, trust, and education from several parties.Statins are not only indicated, but also confer the greatest benefit for secondary prevention.12Banach M Penson PE. Statins and LDL-C in secondary prevention-so much progress, so far to go.JAMA Netw Open. 2020; 3e2025675Crossref PubMed Scopus (17) Google Scholar,24Virani SS Smith Jr, SC Stone NJ Grundy SM. Secondary prevention for atherosclerotic cardiovascular disease: comparing recent US and European guidelines on dyslipidemia.Circ. 2020; 141: 1121-1123Crossref PubMed Scopus (24) Google Scholar Long-term statin use may decrease the risk of cardiovascular death by 50% to 55%.12Banach M Penson PE. Statins and LDL-C in secondary prevention-so much progress, so far to go.JAMA Netw Open. 2020; 3e2025675Crossref PubMed Scopus (17) Google Scholar A multicenter Spanish study echoed that high-intensity statin therapy, regardless of type, was protective against ASCVD events.25Perez-Calahorra S Laclaustra M Marco-Benedi V Pinto X Sanchez-Hernandez RM Plana N Ortega E Fuentes F Civeira F. Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence.Lipids Health Dis. 2019; 18: 216Crossref PubMed Scopus (7) Google Scholar Our findings are reflective of those by Lin and coworkers26Lin I Sung J Sanchez RJ Mallya UG Friedman M Panaccio M Koren A Neumann P Menzin J. Patterns of statin use in a real-world population of patients at high cardiovascular risk.J Manag Care Spec Pharm. 2016; 22: 685-698Crossref PubMed Scopus (52) Google Scholar who found low statin adherence, high statin discontinuation, and a high 2-year rate of ASCVD hospitalizations in a cohort of high risk patients. Another study considered primary and secondary prevention, finding that 20.9% and 43.0% of patients had at least 1 cardiovascular event in a 2 years follow-up, respectively. They also found widespread underuse of statins.27Punekar RS Fox KM Richhariya A Fisher MD Cziraky M Gandra SR Toth PP. Burden of first and recurrent cardiovascular events among patients with hyperlipidemia.Clin Cardiol. 2015; 38: 483-491Crossref PubMed Scopus (29) Google ScholarStatin-associated protection against fatal events was greater in this study than in clinical trials.28Sacks FM Pfeffer MA Moye LA Rouleau JL Rutherford JD Cole TG Brown L Warnica JW Arnold JM Wun CC Davis BR Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.N Engl J Med. 1996; 335: 1001-1009Crossref PubMed Scopus (7173) Google Scholar Randomized clinical trials (RCTs) identify an isolated treatment effect by eliminating extraneous variability (including behavior/adherence). Results from real-world data analyses, such as ours, are important because they represent a constellation of additional factors that occur in patients' lives (unobserved in RCTs).29Ramagopalan SV Simpson A Sammon C. Can real-world data really replace randomized clinical trials?.BMC Med. 2020; 18: 13Crossref PubMed Scopus (24) Google Scholar,30Bartlett VL Dhruva SS Shah ND Ryan P Ross JS Feasibility of using real-world data to replicate clinical trial evidence.JAMA Netw Open. 2019; 2e1912869Crossref Scopus (113) Google Scholar For example, patients who filled scripts may be more likely to engage in healthy lifestyle behaviors.31Náfrádi L Nakamoto K Schulz PJ. Is patient empowerment the key to promote adherence? A systematic review of the relationship between self-efficacy, health locus of control and medication adherence.PLoS One. 2017; 12e0186458Crossref PubMed Scopus (206) Google Scholar Hence, the results observed in this study may also reflect other health behaviors. Due to the nature of our study, patients could not receive a monetary incentive for adhering to a given study protocol, as occurs in RCTs.32Parkinson B Meacock R Sutton M Fichera E Mills N Shorter GW Treweek S Harman NL Brown RCH Gillies K Bower P. Designing and using incentives to support recruitment and retention in clinical trials: a scoping review and a checklist for design.Trials. 2019; 20: 624Crossref PubMed Scopus (26) Google Scholar,33Krutsinger DC McMahon J Stephens-Shields AJ Bayes B Brooks S Hitsman BL Lubitz SF Reyes C Schnoll RA Ryan Greysen S Mercede A Patel MS Reale C Barg F Karlawish J Polsky D Volpp KG Halpern SD Randomized evaluation of trial acceptability by INcentive (RETAIN): study protocol for two embedded randomized controlled trials.Contemp Clin Trials. 2019; 76: 1-8Abstract Full Text Full Text PDF PubMed Scopus (6) Google ScholarThe biggest limitation of this study is its retrospective design. Our data were limited to insurance claims; hence, if a patient filled a prescription without insurance, it was not recorded. Further, script fills are indirect measures of adherence. Similarly, we do not know the rate at which providers prescribed drugs or if patients received drug counseling. Due to the definition of the primary variable of interest, immortal time bias may be present.34Lévesque LE Hanley JA Kezouh A Suissa S. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes.BMJ. 2010; 340: b5087Crossref PubMed Scopus (679) Google Scholar Finally, the study period was chosen to use ICD-9-CM codes; however, newer lipid-lowering therapies are available now.35Feingold KR. Cholesterol lowering drugs.in: Feingold KR Anawalt B Boyce A Endotext. MDText.com, Inc., South Dartmouth, MA2000Google Scholar Strengths of this study include the use of previously published ICD and Current Procedural Terminology code sets, its multicenter design, and robust modeling approach.In conclusion, this study demonstrated a modest increase in statin treatment after an initial ASCVD event, with nearly half of the patients remaining undertreated. When jointly modeling nonfatal and fatal events, we observed that the primary benefit of statin use was protection against early death. Furthermore, because we observed that statin use may have the greatest impact in the first 6 months after an ASCVD event, it is crucial for patients to quickly adhere to therapy.DisclosuresThe authors have no conflicts of interest to declare.FundingThis work was funded by a grant from Amgen Inc. to the Baylor Scott & White Research Institute. IntroductionMillions of adults in the United States (US) are affected by cardiovascular events each year, reducing their quality of life and increasing their risk for death.1Pahwa R Jialal I Atherosclerosis.StatPearls. 2021; Google Scholar Hyperlipidemia is a significant risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), which is present in 47% of young adults with ASCVD.2Virani SS Alonso A Benjamin EJ Bittencourt MS Callaway CW Carson AP Chamberlain AM Chang AR Cheng S Delling FN Djousse L Elkind MSV Ferguson JF Fornage M Khan SS Kissela BM Knutson KL Kwan TW Lackland DT Lewis TT Lichtman JH Longenecker CT Loop MS Lutsey PL Martin SS Matsushita K Moran AE Mussolino ME Perak AM Rosamond WD Roth GA Sampson UKA Satou GM Schroeder EB Shah SH Shay CM Spartano NL Stokes A Tirschwell DL VanWagner LB Tsao CW American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2020 update: a report from the.American Heart Association. Circulation. 2020; 141: e139-e596Google Scholar,3Vikulova DN Grubisic M Zhao Y Lynch K Humphries KH Pimstone SN Brunham LR. Premature atherosclerotic cardiovascular disease: trends in incidence, risk factors, and sex-related differences, 2000 to 2016.J Am Heart Assoc. 2019; 8e012178Crossref PubMed Scopus (43) Google Scholar Lipid-lowering therapy is a cornerstone of secondary ASCVD prevention, but many patients remain untreated. The near-term consequences of medication underutilization after an acute event are not well understood. Although there is a panoply of lipid-lowering therapies, we chose to limit this analysis to the American Heart Association guideline-recommended first-line medication of statins.4Arnett DK Blumenthal RS Albert MA Buroker AB Goldberger ZD Hahn EJ Himmelfarb CD Khera A Lloyd-Jones D McEvoy JW Michos ED Miedema MD Muñoz D Smith SC Virani SS Williams KA Yeboah J Ziaeian B. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Circulation. 2019; 140: e596-e646PubMed Google Scholar Hence, the purpose of this report is to study the association between statin use/nonuse and recurrent major adverse cardiovascular events (MACE) in a cohort of patients across the US who had a recent acute ASCVD event.