Abstract
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=3,626), a myocardial infarction (MI) other than a recent ACS (n=7,572), an ischemic stroke (n=3,551) or symptomatic peripheral artery disease (PAD, n=5,919). 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 1,000 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.
Keywords: cholesterol, guidelines, risk prediction
The 2018 American Heart Association (AHA) and American College of Cardiology (ACC) multi-society guideline on the management of blood cholesterol recommends using risk stratification to guide the intensity of pharmacological lipid-lowering treatment among adults with a history of atherosclerotic cardiovascular disease (ASCVD).1 The guideline recommends individuals with very high ASCVD risk, defined by a history of two or more major ASCVD events or a history of one major ASCVD event with multiple ASCVD risk factors, and low-density lipoprotein cholesterol ≥70 mg/dL while taking maximally-tolerated statin therapy initiate ezetimibe and/or a PCSK9 inhibitor. In two previous studies, those who met versus did not meet the definition for very high risk had two-to-three times higher risk for future ASCVD events.2,3 These studies confirmed the 2018 AHA/ACC cholesterol guideline risk stratification algorithm identifies patients with very high risk for future ASCVD events.
The recommendation of intensive lipid-lowering therapy for patients with a history of ASCVD at very high risk for recurrent events will direct the most intensive treatment to patients likely to receive the largest risk reduction benefit.4,5 While risk stratification can facilitate the tailoring of treatment recommendations, using algorithms to guide treatment may complicate treatment decision making.6-8 Healthcare providers may benefit from a simplified approach for determining whether a patient has very high ASCVD risk. We hypothesized that the vast majority of patients with a history of a major ASCVD event would meet the 2018 AHA/ACC guideline definition for very high risk. This would allow healthcare providers to easily identify a subset of patients meeting the very high risk definition. The goal of the current study was to estimate the proportion of patients with a history of a major ASCVD event that meet the criteria for very high risk and may be candidates for intensive lipid-lowering therapy. Additionally, we estimated the ASCVD event rates for all patients who had previously experienced a major ASCVD event and those who met the 2018 AHA/ACC cholesterol guideline definition for very high risk.
Methods
We conducted a retrospective cohort study of adults using data from the MarketScan database (Truven Health Analytics, IBM Watson Health). The MarketScan database contains data for patients in the US with commercial or Medicare supplemental health insurance. We obtained patient-level information from the MarketScan administrative database linked to LDL cholesterol values, maintained by Quest Diagnostics for the calendar years 2015 through 2017. The Institutional Review Board at the University of Alabama at Birmingham approved the study and waived the requirement to obtain informed consent.
The analysis was restricted to Marketscan beneficiaries 19 years of age or older on December 31, 2015. Additionally, we restricted the analysis to patients with a history of major ASCVD on December 31, 2015 defined according to the 2018 AHA/ACC cholesterol guideline as a recent acute coronary syndrome (ACS, i.e., acute MI or unstable angina), history of MI other than recent ACS, history of ischemic stroke or symptomatic PAD (i.e., a history of PAD with claudication, gangrene or ulceration, peripheral artery revascularization or major amputation secondary to PAD).1 Definitions for these conditions are provided in Online Table 1. We used beneficiary enrollment data from the health insurance claims to determine patients’ age and sex. Heterozygous familial hypercholesterolemia, prior coronary artery bypass surgery or percutaneous coronary intervention outside of a major ASCVD event, diabetes mellitus, hypertension, chronic kidney disease (CKD), current smoking, and heart failure were defined using health insurance claims in the Marketscan database on or before December 31, 2015. Definitions of these characteristics are provided in Online Table 2. Persistently elevated LDL cholesterol was defined by LDL cholesterol ≥ 100 mg/dL with concurrent moderate or high-intensity statin use and ezetimibe. Laboratory data were available for patients in the MarketScan database through linkage with the Quest Diagnostics laboratory database. LDL cholesterol values between January 1, 2015 and January 1, 2016 were used for this analysis. We used pharmacy claims to identify fills for a statin (i.e., atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin or simvastatin) or ezetimibe between January 1, 2015 and January 1, 2016. Use of a high-intensity statin in combination with ezetimibe was defined by having both a high-intensity statin and ezetimibe available to take on at least one day in 2015. Pharmacy fills for atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg, or simvastatin 80 mg were used to define a high-intensity statin. The definition for very high risk followed the 2018 AHA/ACC blood cholesterol guideline and included a history of multiple major ASCVD events or one major ASCVD event in addition to multiple high-risk conditions (Table 1).
Table 1.
Definition of major atherosclerotic cardiovascular disease events and high-risk conditions in the 2018 AHA/ACC blood cholesterol guideline.
| Major atherosclerotic cardiovascular disease events | |
|---|---|
| 1. | Recent acute coronary syndrome within the past 12 months |
| 2. | History of myocardial infarction other than a recent acute coronary syndrome event |
| 3. | History of ischemic stroke |
| 4. | Symptomatic peripheral arterial disease |
|
| |
| High-risk conditions | |
|
| |
| 1. | Age ≥ 65 years |
| 2. | Heterozygous familial hypercholesterolemia |
| 3. | History of prior coronary artery bypass surgery or percutaneous coronary intervention outside of the major atherosclerotic cardiovascular disease event(s) |
| 4. | Diabetes mellitus |
| 5. | Hypertension |
| 6. | Chronic kidney disease defined by an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m2 |
| 7. | Current smoking |
| 8. | Persistently elevated LDL cholesterol defined by LDL cholesterol ≥100 mg/dL despite maximally-tolerated statin therapy and ezetimibe |
| 9. | History of congestive heart failure |
LDL: low-density lipoprotein
Symptomatic peripheral arterial disease includes a history of claudication with ankle-brachial index <0.85, or previous revascularization or amputation
We followed patients for their first ASCVD event including MI, ischemic stroke or major adverse limb events with censoring occurring upon loss of health insurance benefits or December 31, 2017. The algorithms used to define the occurrence of these events are listed in Online Table 3. We censored patients upon loss of inpatient or outpatient health insurance, in-hospital death or December 31, 2017, whichever occurred first. Data on out-of-hospital death were not available in the Marketscan database.
Statistical analysis
All calculations were done for patients with a history of major ASCVD, overall, and among patients who had experienced a recent ACS, history of MI, history of ischemic stroke and with symptomatic PAD, separately. We summarized the characteristics of patients with a history of a major ASCVD event. The proportion of patients with a history of a major ASCVD event who met the definition for very high risk was calculated for the overall study population and for women and men, separately. Additionally, we calculated the proportion of patients who had experienced only one prior major ASCVD event who met the definition for very high risk. We calculated the rate of ASCVD events among all patients with a history of a major ASCVD event and for patients with a history of a major ASCVD event who met the 2018 AHA/ACC cholesterol guideline definition of very high ASCVD risk. ASCVD event rates were also calculated for women and men, separately, and for patients taking a high-intensity statin, ezetimibe and a high-intensity statin with ezetimibe. Analyses were conducted using SAS v. 9.4.
Results
We studied 16,344 patients who had a history of a major ASCVD event. The mean age of patients was 67.7 years and 38.5% were female (Table 2). Overall, 22.2%, 46.3%, 21.7% and 36.2% had a history of ACS, MI other than ACS, ischemic stroke and PAD, respectively. Hypertension was the most common high-risk condition and was present among 93.2% of patients with a history of a major ASCVD event. A majority of patients were ≥ 65 years of age (54.5%), had a prior PCI or CABG (51.2%) and diabetes mellitus (51.9%). Also, 66.8% had an LDL-C ≥ 70 mg/dL, 80.2% were taking a statin (35.3% taking a high-intensity statin), 6.8% were taking ezetimibe and 2.6% were taking a high-intensity statin and ezetimibe. Patients with a history of ischemic stroke and symptomatic PAD were older, more likely to be women, less likely to have commercial health insurance and less likely to be taking a high-intensity statin than their counterparts with a recent ACS or MI other than a recent ACS. The most common dyads of high-risk conditions are provided in Online Table 4. During follow-up, 12.9% of patients with any ASCVD event who were not taking a high-intensity statin at the beginning of follow-up initiated a high-intensity statin during follow-up (Online Table 5). Also, 2.5% of patients initiated ezetimibe and 1.6% initiated a high-intensity statin in conjunction with ezetimibe.
Table 2.
Characteristics of patients with a history of a major atherosclerotic cardiovascular disease event by type of event experienced.
| Any ASCVD Event n=16,344 | Recent ACS n=3,626 | Acute MI n=7,572 | Acute IS n=3,551 | Symptomatic PAD n=5,919 | |
|---|---|---|---|---|---|
| Age, years, mean (SD) | 67.7 (12.1) | 65.5 (12.2) | 68.0 (11.6) | 69.1 (12.8) | 70.2 (11.3) |
| Female | 6,293 (38.5) | 1,319 (36.4) | 2,498 (33.0) | 1,693 (47.7) | 2,408 (40.7) |
| Commercial health insurance | 7,141 (43.7) | 1,914 (52.8) | 3,217 (42.5) | 1,349 (38.0) | 1,988 (33.6) |
| Geographic region of residence | |||||
| Midwest | 4,063 (24.9) | 822 (22.7) | 2,152 (28.4) | 887 (25.0) | 1,505 (25.4) |
| Northeast | 2,651 (16.2) | 650 (17.9) | 1,096 (14.5) | 550 (15.5) | 1,005 (17.0) |
| South | 5,072 (31.0) | 1,184 (32.7) | 2,203 (29.1) | 1,125 (31.7) | 1,695 (28.6) |
| West | 986 (6.0) | 243 (6.7) | 468 (6.2) | 221 (6.2) | 290 (4.9) |
| Missing | 3,572 (21.9) | 727 (20.0) | 1,653 (21.8) | 768 (21.6) | 1,424 (24.1) |
| Major ASCVD events | |||||
| At least 1 recent ACS event | 3,626 (22.2) | 3,626 (100) | 714 (9.4) | 339 (9.5) | 656 (11.1) |
| At least 1 MI | 7,572 (46.3) | 714 (19.7) | 7,572 (100) | 828 (23.3) | 1,706 (28.8) |
| At least 1 IS event | 3,551 (21.7) | 339 (9.3) | 828 (10.9) | 3,551 (100) | 750 (12.7) |
| Symptomatic PAD | 5,919 (36.2) | 656 (18.1) | 1,706 (22.5) | 750 (21.1) | 5,919 (100) |
| High-risk conditions | |||||
| Age ≥ 65 years | 8,913 (54.5) | 1,656 (45.7) | 4,219 (55.7) | 2,139 (60.2) | 3,789 (64.0) |
| Heterozygous FH | 506 (3.1) | 132 (3.6) | 224 (3.0) | 119 (3.4) | 169 (2.9) |
| Prior CABG or PCI | 8,374 (51.2) | 1,641 (45.3) | 5,594 (73.9) | 1,053 (29.7) | 2,865 (48.4) |
| Diabetes mellitus | 8,490 (51.9) | 1,822 (50.2) | 3,958 (52.3) | 1,918 (54.0) | 3,577 (60.4) |
| Hypertension | 15,233 (93.2) | 3,333 (91.9) | 7,219 (95.3) | 3,352 (94.4) | 5,579 (94.3) |
| Chronic kidney disease | 5,012 (30.7) | 1,027 (28.3) | 2,455 (32.4) | 1,227 (34.6) | 2,223 (37.6) |
| Current smoking | 2,436 (14.9) | 624 (17.2) | 1,058 (14.0) | 497 (14.0) | 1,020 (17.2) |
| Persistently elevated LDL cholesterol | 5,107 (31.2) | 1,195 (33.0) | 2,024 (26.7) | 1,224 (34.5) | 1,891 (31.9) |
| Heart failure | 5,068 (31.0) | 1,393 (38.4) | 2,817 (37.2) | 1,187 (33.4) | 1,955 (33.0) |
| Medication use | |||||
| Any statin | 13,100 (80.2) | 3,071 (84.7) | 6,280 (82.9) | 2,830 (79.7) | 4,521 (76.4) |
| High-intensity statin | 5,762 (35.3) | 1,693 (46.7) | 2,888 (38.1) | 1,096 (30.9) | 1,668 (28.2) |
| Ezetimibe | 1,107 (6.8) | 188 (5.2) | 641 (8.5) | 171 (4.8) | 439 (7.4) |
| High-intensity statin and ezetimibe | 417 (2.6) | 77 (2.1) | 264 (3.5) | 58 (1.6) | 144 (2.4) |
| LDL cholesterol ≥ 70 mg/dL | |||||
| Overall | 10,920 (66.8) | 2,386 (65.8) | 4,821 (63.7) | 2,449 (69.0) | 3,984 (67.3) |
| Among those taking: | |||||
| High-intensity statin | 3,332/5,762 (57.8) | 969/1,693 (57.2) | 1,628/2,888 (56.4) | 674/1,096 (61.5) | 956/1,668 (57.3) |
| High-intensity statin without ezetimibe | 3,091/5,345 (57.8) | 925/1,616 (57.2) | 1,466/2,624 (55.9) | 641/1,038 (61.8) | 882/1,524 (57.9) |
| High-intensity statin and ezetimibe | 241/417 (57.8) | 44/77 (57.1) | 162/264 (61.4) | 33/58 (56.9) | 74/144 (51.4) |
ACS - acute coronary syndrome, ASCVD – Atherosclerotic cardiovascular disease, CABG – coronary artery bypass grafting, FH - familial hypercholesterolemia, IS - ischemic stroke, LDL – low density lipoprotein, MI - myocardial infarction, PAD - peripheral artery disease, PCI – percutaneous coronary intervention.
Major atherosclerotic cardiovascular disease events included a recent acute coronary syndrome, history of myocardial infarction other than a recent acute coronary syndrome, history of ischemic stroke and symptomatic peripheral artery disease. Symptomatic PAD included a history of PAD with claudication, gangrene or ulceration, peripheral artery revascularization or major amputation secondary to PAD. Some patients had more than one major atherosclerotic cardiovascular disease events and are included in multiple columns.
Numbers in the table are n (%) except for age which is mean (standard deviation).
Overall, 15,366 (94.0%) of 16,344 patients with a history of a major ASCVD event met the 2018 AHA/ACC cholesterol guideline definition for very high risk. Across each type of major ASCVD event including recent ACS, history of MI other than recent ACS, history of ischemic stroke or symptomatic PAD, over 90% of patients met the definition for very high risk (Figure 1). By definition, 100% of patients who had experienced two or more major ASCVD events met the criteria for very high risk. Also, 92.1% of patients who had experienced only one ASCVD event met the definition of very high risk.
Figure 1.
Proportion of patients with a history of a major atherosclerotic cardiovascular disease event including a recent acute coronary syndrome, myocardial infarction, ischemic stroke or symptomatic peripheral artery disease that meet the definition for being very high risk according to the 2018 AHA/ACC cholesterol guideline.
Among patients who had experienced only one major ASCVD event, 89.0%, 94.4%, 88.3% and 93.3% of those who had recent ACS, history of MI, history of ischemic stroke and symptomatic PAD met the definition of very high risk, respectively. Among women and men with a history of a major ASCVD event, 93.9% and 94.1% met the 2018 AHA/ACC cholesterol guideline definition for very high risk, respectively (Online Figure 1 for women and Online Figure 2 for men).
Over the 2-year follow-up period, 1,227 patients experienced a recurrent ASCVD event. The ASCVD event rates were 50.4 per 1,000 person-years among all patients with a history of a major ASCVD event and 53.1 per 1,000 person-years among those who met the 2018 AHA/ACC cholesterol guideline definition for very high risk (Table 3). Among women with a history of a major ASCVD event and who met the 2018 AHA/ACC cholesterol guideline definition for very high risk ASCVD, the event rates were 50.3 and 53.1 per 1,000 person-years, respectively, and the event rates were 50.4 and 53.0 per 1,000 person-years, respectively, among men. The ASCVD event rates were within 5 events per 1,000 person-years between all patients with a recent ACS, history of MI, history of ischemic stroke and symptomatic PAD and their counterparts with each condition who met the 2018 AHA/ACC cholesterol guideline definition for very high risk. The ASCVD event rates for all patients with a history of a major ASCVD event and the subset who met the 2018 AHA/ACC cholesterol guideline definition for very high risk in sub-groups of those taking a high-intensity statin, ezetimibe and a high-intensity statin and ezetimibe are provided in Online Table 6.
Table 3.
Rates of atherosclerotic cardiovascular disease events among patients with a history of a major atherosclerotic cardiovascular disease event, recent acute coronary syndrome, myocardial infarction, ischemic stroke or symptomatic peripheral artery disease, overall and that meet the definition for being very high risk according to the 2018 AHA/ACC cholesterol guideline.
| History of a Major ASCVD Event | Type of major ASCVD event | ||||
|---|---|---|---|---|---|
|
| |||||
| Any (n=16,344) | Recent ACS (n=3,626) | History of MI (n=7,572) | History of IS (n=3,551) | Symptomatic PAD (n=5,919) | |
| Overall | Rate (95% confidence interval) per 1,000 person years | ||||
| Overall population | 50.4 (47.6, 53.3) | 64.0 (57.6, 71.2) | 51.5 (47.5, 55.9) | 58.2 (51.9, 65.3) | 69.3 (63.9, 75.1) |
| Very high risk | 53.1 (50.1, 56.1) | 68.6 (61.6, 76.3) | 53.2 (49.0, 57.7) | 62.6 (55.8, 70.2) | 71.3 (65.7, 77.3) |
| Women | Rate (95% confidence interval) per 1,000 person years | ||||
| Overall population | 50.3 (46.0, 55.1) | 70.9 (60.0, 83.8) | 54.8 (47.8, 62.9) | 53.8 (45.3, 63.9) | 63.0 (55.2, 71.9) |
| Very high risk | 53.1 (48.5, 58.2) | 75.2 (63.5, 89.0) | 56.2 (48.9, 64.5) | 58.2 (49.0, 69.2) | 65.6 (57.5, 75.0) |
| Men | Rate (95% confidence interval) per 1,000 person years | ||||
| Overall population | 50.4 (46.9, 54.1) | 60.2 (52.5, 68.9) | 49.9 (45.2, 55.2) | 62.2 (53.4, 72.5) | 73.7 (66.5, 81.5) |
| Very high risk | 53.0 (49.4, 57.0) | 64.8 (56.5, 74.3) | 51.7 (46.7, 57.2) | 66.5 (57.1, 77.5) | 75.1 (67.8, 83.2) |
ACC – American College of Cardiology, AHA – American Heart Association, ACS - acute coronary syndrome, ASCVD – Atherosclerotic cardiovascular disease, IS - ischemic stroke, MI - myocardial infarction, PAD - peripheral artery disease.
Very high risk is defined according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline as having multiple, two or more, major atherosclerotic cardiovascular disease events or one major atherosclerotic cardiovascular disease event and, two or more, high-risk conditions.
Discussion
In this study, more than 90% of patients with a recent ACS, history of MI other than a recent ACS, history of ischemic stroke or symptomatic PAD met the definition in the 2018 AHA/ACC guideline for very high risk. Regardless of the type of major ASCVD event that patients had experienced, the ASCVD event rate was very high. Additionally, the ASCVD event rates were similar among all patients with a history of a major ASCVD event and among patients who met the 2018 AHA/ACC cholesterol guideline definition of very high risk.
The 2018 AHA/ACC cholesterol guideline risk stratification algorithm identifies patients with a very high risk for future ASCVD events.1 In a secondary analysis of the ODYSSEY outcomes trial, the rate of major adverse cardiovascular events was 54.8 and 20.4 per 1,000 person-years among participants who met and did not meet the 2018 AHA/ACC cholesterol guideline definition of very high risk, respectively.3 In a previous analysis of the MarketScan database, the ASCVD event rate for those meeting versus not meeting the definition for very high risk was 53.1 versus 17.0 per 1,000 person-years, respectively.2 In the current study, the risk for ASCVD events was similar among all patients with a history of a major ASCVD event and those who met the 2018 AHA/ACC cholesterol guideline definition for very high risk. This is not surprising as over 90% of patients with a history of a major ASCVD event met the 2018 AHA/ACC cholesterol guideline definition for very high risk.
Based on data from the National Health and Nutrition Examination Survey (NHANES), over 15 million US adults have a history of a MI or stroke suggesting a large number of patients in the US may be eligible for the 2018 AHA/ACC cholesterol guideline recommendation for lipid-lowering therapy with a high-intensity statin and ezetimibe and/or a PCSK9 inhibitor.9 While we estimated that the risk for recurrent ASCVD events is very high in this population, it may be useful to further identify the patients with a history of a major ASCVD event who benefit most from intensive lipid-lowering treatment with ezetimibe and a PCSK9 inhibitor. Other guidelines provide different definitions of very high risk for recurrent ASCVD events and recommending intensive lipid-lowering treatment.10,11 For example, the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) cholesterol guideline recommends consideration of an LDL-C goal < 40 mg/dL for patients with ASCVD who experience a second vascular event within two years of an initial event.11 This recommendation is supported by subgroup analyses of FOURIER and ODYSSEY Outcomes. Future studies should evaluate the risk for ASCVD events and assess the risk reduction benefit of ezetimibe and a PCSK9 inhibitor in this population.
The current study focused on the definition of very high risk in the 2018 AHA/ACC cholesterol guideline. The 2019 ESC/EAS cholesterol guideline defines very high risk by the presence of documented ASCVD, diabetes mellitus with target organ damage, severe CKD and familial hypercholesterolemia with ASCVD or another risk factor.11 For patients with ASCVD risk deemed to have very-high risk, and LDL-C reduction of ≥ 50% and LDL-C goal of < 55 mg/dL is recommended. These goals are also recommended for patients with very high risk without familial hypercholesterolemia and should be considered for patients with familial hypercholesterolemia. Future studies should evaluate whether a simplified approach can be used to identify patients with very high risk as defined in the 2019 ESC/EAS cholesterol guideline.
In the current study, less than 50% of patients were taking a high-intensity statin and only 2.6% were taking a high-intensity statin and ezetimibe and only a small proportion of patients initiated these medications during follow-up. The baseline period for this study ended on December 31, 2015, and the proportion of patients filling prescriptions for a high-intensity statin has increased following hospital discharge for MI in the US and Europe.12,13 However, many patients discontinue or down-titrate statin therapy soon after initiation.12,14 The low proportion of patients with a history of major ASCVD events taking a high-intensity statin and ezetimibe indicates a need for strategies to increase the initiation of, and adherence to, intensive lipid-lowering therapies among patients with a history of major ASCVD events.
The degree to which the 2018 AHA/ACC cholesterol guideline algorithm for identifying very high risk patients will be used is unclear. Physicians have reported barriers to using the results of prediction models including the decision-making process being intuitive rather than analytical, difficulty in applying the results in decision-making and the results do not adequately weigh benefits and risks of subsequent treatment.15,16 As more than 90% of patients who had a recent ACS, history of MI other than recent ACS, history of ischemic stroke, or symptomatic PAD met the AHA/ACC definition for very high risk, clinicians can reasonably assume that the vast majority of their patients with a history of major ASCVD are very high risk without applying an algorithm.
There are several strengths associated with this study. This includes its large sample size and inclusion of patients from across the US. Therefore, this study has broad generalizability to US adults with a history of major ASCVD events. Additionally, we had two years of follow up for recurrent ASCVD events. This study has known and potential limitations. The applicability of the results to individuals outside of the US or without health insurance is unknown. We relied on insurance claims to define major ASCVD events and high-risk conditions. While claims have a high positive predictive value for many of these conditions, some algorithms have low sensitivity.17–19 Therefore, a higher proportion of patients with major ASCVD events than we report may meet the definition for very high risk.
In conclusion, over 90% of patients with a recent ACS, history of MI other than recent ACS, history of ischemic stroke or symptomatic PAD in the current study met the 2018 AHA/ACC cholesterol definition for very high risk for future ASCVD events. The ASCVD incidence rate was similar among patients with a history of a major ASCVD event and those who met the 2018 AHA/ACC cholesterol guideline definition for very high risk. These data suggest that patients with a history of a major ASCVD event can be assumed to have very high risk for future events without applying additional risk stratification algorithms.
Supplementary Material
Funding:
The design and conduct of the study, interpretation of the results, and preparation of the manuscript was supported through a grant from Amgen, Inc. (Thousand Oaks, CA).
Conflicts of interest/competing interests:
KKO, KEM, JE, EDS and RZ are employed by Amgen, Inc. KKO, KEM, and JE also have stock in Amgen, Inc. EAJ, RSR and PM receive research support from Amgen, Inc. RSR also receives research support from the Medicines Company, Novartis, Novo Nordisk and Regeneron; consulting fees from Amgen, C5, CVS Caremark and Corvidia; honoraria from Amgen, Kowa, Pfizer, Regeneron and 89bio; royalties from UpToDate, Inc.; and has stock ownership in MediMergent, LLC. EAJ receives royalties from UpToDate.
Footnotes
Publisher's Disclaimer: This Author Accepted Manuscript is a PDF file of a an unedited peer-reviewed manuscript that has been accepted for publication but has not been copyedited or corrected. The official version of record that is published in the journal is kept up to date and so may therefore differ from this version.
Ethics approval: Institutional review board was received from the University of Alabama at Birmingham.
Consent to participate: Data used for this study were obtained as part of routine clinical care. The requirement of consent was waived by the institutional review board for the analysis of de-identified data.
Consent for publication: The academic authors maintained the right to publish these data.
Code availability: Statistical code can be obtained by contacting the authors.
Availability of data and material:
The data used in the current analysis can be licensed from Truven Health Analytics, IBM Watson Health.
References
- 1.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: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):3168–3209. [DOI] [PubMed] [Google Scholar]
- 2.Colantonio LD, Shannon ED, Orroth KK, et al. Ischemic Event Rates in Very-High-Risk Adults. J Am Coll Cardiol. 2019;74(20):2496–2507. [DOI] [PubMed] [Google Scholar]
- 3.Roe MT, Li QH, Bhatt DL, et al. Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes. Circulation. 2019;140(19):1578–1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.van der Leeuw J, Ridker PM, van der Graaf Y, Visseren FL. Personalized cardiovascular disease prevention by applying individualized prediction of treatment effects. Eur Heart J. 2014;35(13):837–843. [DOI] [PubMed] [Google Scholar]
- 5.Cholesterol Treatment Trialists C, Mihaylova B, Emberson J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–590. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Salisbury AC, Spertus JA. Realizing the Potential of Clinical Risk Prediction Models: Where Are We Now and What Needs to Change to Better Personalize Delivery of Care? Circ Cardiovasc Qual Outcomes. 2015;8(4):332–334. [DOI] [PubMed] [Google Scholar]
- 7.Eichler K, Zoller M, Tschudi P, Steurer J Barriers to apply cardiovascular prediction rules in primary care: a postal survey. BMC Fam Pract. 2007;8:1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Whittaker R, Bramley D, Wells S, et al. Will a web-based cardiovascular disease (CVD) risk assessment programme increase the assessment of CVD risk factors for Maori? N Z Med J. 2006;119(1238):U2077. [PubMed] [Google Scholar]
- 9.Benjamin EJ, Muntner P, Alonso A, et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019;139(10):e56–e528. [DOI] [PubMed] [Google Scholar]
- 10.Solnica B, Sygitowicz G, Sitkiewicz D, et al. 2020 Guidelines of the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA) on laboratory diagnostics of lipid metabolism disorders. Arch Med Sci. 2020;16(2):237–252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.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 (1):111–188. [DOI] [PubMed] [Google Scholar]
- 12.De Backer G, Jankowski P, Kotseva K, et al. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis. 2019;285:135–146. [DOI] [PubMed] [Google Scholar]
- 13.Rosenson RS, Farkouh ME, Mefford M, et al. Trends in Use of High-Intensity Statin Therapy After Myocardial Infarction, 2011 to 2014. J Am Coll Cardiol. 2017;69(22):2696–2706. [DOI] [PubMed] [Google Scholar]
- 14.Colantonio LD, Huang L, Monda KL, et al. Adherence to High-Intensity Statins Following a Myocardial Infarction Hospitalization Among Medicare Beneficiaries. JAMA Cardiol. 2017;2(8):890–895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Kappen TH, van Loon K, Kappen MA, et al. Barriers and facilitators perceived by physicians when using prediction models in practice. J Clin Epidemiol. 2016;70:136–145. [DOI] [PubMed] [Google Scholar]
- 16.Muller-Riemenschneider F, Holmberg C, Rieckmann N, et al. Barriers to routine risk-score use for healthy primary care patients: survey and qualitative study. Arch Intern Med. 2010;170(8):719–724. [DOI] [PubMed] [Google Scholar]
- 17.Colantonio LD, Levitan EB, Yun H, et al. Use of Medicare Claims Data for the Identification of Myocardial Infarction: The Reasons for Geographic And Racial Differences in Stroke Study. Med Care. 2018;56(12):1051–1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Muntner P, Gutierrez OM, Zhao H, et al. Validation study of medicare claims to identify older US adults with CKD using the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Am J Kidney Dis. 2015;65(2):249–258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Kumamaru H, Judd SE, Curtis JR, et al. Validity of claims-based stroke algorithms in contemporary Medicare data: reasons for geographic and racial differences in stroke (REGARDS) study linked with medicare claims. Circ Cardiovasc Qual Outcomes. 2014;7(4):611–619. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data used in the current analysis can be licensed from Truven Health Analytics, IBM Watson Health.