Prevalence of atherosclerotic cardiovascular disease and subsequent major adverse cardiovascular events in Alberta, Canada: A real‐world evidence study

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5‐year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada. Methods A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five‐year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One‐year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined. Results There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5‐year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1‐year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03–6.26) per 100 person‐years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45–15.20) per 100 person‐years. Conclusions This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD.


| INTRODUCTION
ASCVD continues to be a leading cause of morbidity and mortality worldwide. 1 A global mortality rate of over 17.9 million people is associated with cardiovascular (CV) diseases annually, accounting for 31% of overall deaths per year. 2 Similarly, in Canada, not only is ASCVD the second leading cause of death following cancer, but the 10-year risk of a CV event was 8.9%. 3,4 In addition to the considerable impact on patient health, the global cost of ASCVD in 2010 was estimated to be $863 billion USD. 1 Although estimates of the financial burden of ASCVD across Canada are lacking, a recent study conducted in Ontario, Canada reported the cost associated with newly diagnosed ASCVD was $66.6 billion CAD between 2005 and 2016, 5 further highlighting the burden of ASCVD on the Canadian healthcare system.
Recent trends also suggest that mortality rates, among those with ASCVD, are rising due to an increasing prevalence of cardiometabolic risk factors, such as diabetes and obesity, 6,7 and the risk of recurrent CV events. 8 Pre-existing ASCVD has been shown to predict recurrent CV events in the same or different arteries or arterial beds. 9 Several trials investigating patients with already established acute coronary syndromes (ACS) found that the rate of subsequent CV events over 8-17 months was 7.5%-19.9%. [10][11][12][13][14][15] Similarly, when pooling individual patient-level data from four post-ACS trials of 46 694 patients with a median follow-up of 358 days, the rate of myocardial infarction (MI), stroke, or CV death combined was 9.2%, with MI events being the most reported event at 5.8%. 16 In addition, this study reported that almost one-third of patients with a first event, then had a subsequent event; a subsequent MI was the most common secondary event among those with an initial MI. 16 A Canadian study reported that acute MI (AMI) had one of the highest rates of hospitalization, especially among men, 17 relative to other CV events. Although preventative strategies, such as lipid-lowering therapies (LLT) and lifestyle modifications are wellestablished and recommended to improve patient outcomes, 18 there remains a high residual risk for recurrent MACE outcomes, and in particular, more severe ASCVD conditions, such as AMI. 16,17,19 Although previous publications worldwide have examined the burden of ASCVD, there is limited Canadian evidence evaluating the burden of ASCVD and subsequent MACE outcomes, including studies with real-world data. 20 In particular, some evidence has shown that patients outside of a clinical trial setting (i.e., realworld studies) experience more severe outcomes. 21,22 Therefore, the aim of the current study was to confirm the findings in previous literature that subsequent MACE outcomes among patients with clinical ASCVD are substantial, utilizing real-world population-based data from the Albertan health system. The objectives of the study were to estimate the 5-year period prevalence of ASCVD in Alberta, to describe the 1-year incidence of subsequent MACE outcomes after an ASCVD event, and to examine a subgroup of patients with AMI as their index ASCVD event.
index ASCVD diagnostic event. Since this AMI subgroup was derived based on the index ASCVD event within the study period, the subgroup does not represent the total AMI population in Alberta.  (Table S3). Subsequent MACE outcomes occurring within the first 30-days of the ASCVD diagnosis index date were excluded to remove any follow-up records attributed to the initial ASCVD diagnostic event. Demographic and clinical characteristics were reported descriptively for the overall ASCVD population and for the subgroup of patients with an AMI as their index event. The 1-year incidence rates (IRs) and corresponding 95% confidence intervals (CIs) of subsequent MACE outcomes were also calculated (events/100 person-years). All statistical analyses presented here were performed in SAS ® version 9.4.

| ASCVD period prevalence
The 5-year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons ( Figure 1). The prevalence of ASCVD was higher in males than females (103.3 vs. 76.2 per 1000 persons) and increased with age. The highest prevalence was observed among males over the age of 75 years (477.2 per 1000 persons). The mean (standard deviation [SD]) age of the ASCVD study cohort was 63.9 (15.6) years (Table 1). Approximately half of the study cohort (49.5%) were ≥ 65 years old at their index date, 56.6% were male, and most patients (64.8%) had a CCI score of ≥1. Just under half of the study cohort (47.5%; n = 94 252) received statin therapy within the first 6 months following ASCVD index date; among those, almost all were prescribed moderate-or high-intensity statins (96.9%).

| Study cohort and characteristics
In the subgroup analysis, patients with an AMI index event were slightly older (mean age [SD] of 67.9 [15.4] years), had a higher proportion of patients with a CCI score of ≥1 (100%), and a greater proportion receiving statin therapy within 6 months of index (69.3%), relative to the overall ASCVD cohort.

| Subsequent MACE outcome rates
Within the overall ASCVD cohort, the proportion of patients with a subsequent primary and secondary MACE outcome 30 days after and within 1-year following ASCVD diagnosis were 5.7% and 3.4%, respectively, and the most common individual MACE outcome was coronary revascularization (2.6%) (

| DISCUSSION
This study examined real-world data from the health system of Alberta, Canada to describe the prevalence of ASCVD, as well as the rate of subsequent MACE outcomes following an initial ASCVD event and within a subgroup of patients with an index AMI event. The 5- year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons, or 8.99%, which aligns with previously published data from Statistics Canada reporting the 10-year risk of a CV disease event to be 8.9%. 4 Further, our study followed similar trends to the global burden of ASCVD, regarding higher rates of ASCVD prevalence among males and those with increasing age. 1 In the overall ASCVD incident cohort, the 1-year rate for subsequent primary and secondary MACE outcomes were 6.15 and 3.67 Given the substantial burden of ASCVD and AMI across populations, secondary prevention efforts are essential for patient management. The most studied modifiable risk factor of CV disease is low-density lipoprotein cholesterol (LDL-C). 27 Canadian guidelines recommend statins for all patients with established ASCVD, additionally, ezetimibe and PCSK9 inhibitors are recommended to lower LDL-C, 28 and decrease the risk of subsequent CV events in ASCVD patients above the LDL-C threshold of 1.8 mmol/L. 18,[29][30][31] However, despite an emphasis on secondary prevention of CV events with lipidlowering therapies, there remains a high residual risk for recurrent MACE outcomes and a substantial overall ASCVD burden. 19 Our study found that only 47.5% of patients with ASCVD and 69.3% of patients with an AMI event received statin therapy within 6 months after their events. Recent international guidelines have recognized the T A B L E 2 One-year subsequent MACE outcome incidence rates/100 person-years in patients with ASCVD overall and the subgroup of patients with an index AMI event importance of additional LLTs to ensure patients with ASCVD achieve guideline-recommended LDL-C goal levels 18,28,32