Current guidelines recommend the measurement of fasting lipid profile and use of statins in all patients with acute coronary syndrome (ACS). However, the temporal trends of lipid testing and statin therapy in “real-world” patients with ACS are unclear. From January 1999 through December 2008, the prospective, multicenter, Global Registry of Acute Coronary Events (GRACE/GRACE 2 /CANRACE) enrolled 13,947 patients with ACS in Canada. We stratified the study population based on year of presentation into 3 groups (1999 to 2004, 2005 to 2006, and 2007 to 2008) and compared the use of lipid testing and use of statin therapy in hospital. Overall, 70.8% of patients underwent lipid testing and 79.4% received in-hospital statin therapy; these patients were younger and had lower GRACE risk scores (p <0.001 for the 2 comparisons) compared to those who did not. Over time there was a significant increase in rates of in-hospital statin therapy (70% in 1999 to 2004 to 84.5% in 2007 to 2008, p for trend < 0.001) but only a minor increase in rates of lipid testing (69.4% in 1999 to 2004 to 72.4% in 2007 to 2008, p for trend = 0.003). After adjusting for confounders, this increasing temporal trend remained statistically significant for statin therapy (p <0.001) but not for lipid testing. Lipid testing was independently associated with in-hospital statin use (adjusted odds ratio 1.62, 95% confidence interval 1.27 to 2.08, p <0.001). In patients who did have lipid testing, those with low-density lipoprotein cholesterol level >130 mg/dl (3.4 mmol/L) were more likely to be treated with in-hospital statins. In conclusion, there has been a significant temporal increase in the use of in-hospital statin therapy but only a minor increase in lipid testing. Lipid testing was strongly associated with in-hospital statin use. A substantial proportion of patients with ACS, especially those at higher risk, still do not receive these guideline-recommended interventions in contemporary practice.
Several studies have shown that lipid-lowering therapies and lipid screening are, in real-life practice, underused in patients with acute coronary syndrome (ACS), although there seems to be a trend toward increased statin prescription on discharge of patients with ACS. However, there are limited data on the contemporary use of in-hospital lipid testing and statin therapy in patients with ACS since the publication of landmark statin trials. Using data from the Global Registry of Acute Coronary Events (GRACE and GRACE 2 ) and the Canadian Registry of Acute Coronary Events (CANRACE), we aimed to examine temporal trends in the use of lipid testing and statin therapy in hospital and the impact of lipid testing on in-hospital statin use in patients across the spectrum of ACS in Canada.
Methods
GRACE was established as a multinational prospective registry to describe the epidemiology, treatment patterns, and clinical outcomes of an unselected population of patients with the entire spectrum of ACS. Details of GRACE have been published previously. In brief, patients were eligible for enrollment into GRACE if they were ≥18 years old, alive at the time of presentation, and admitted with a presumptive diagnosis of ACS based on history and ≥1 of the following: abnormal cardiac biomarkers, electrocardiographic changes consistent with ACS, and/or documented history of coronary artery disease. Patients with ACS precipitated or accompanied by co-morbidities such as surgery, trauma, or gastrointestinal bleeding were excluded. Using predefined criteria, final ACS diagnosis was classified as ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina pectoris (UAP).
Enrolling sites were encouraged to consecutively recruit the first 10 to 20 eligible patients each month. Trained personnel at each site collected data using standardized case-report forms that captured patient demographics, medical history, clinical characteristics, electrocardiographic and other laboratory findings, medical therapies and interventional procedures, and in-hospital outcomes.
The original GRACE was expanded in 2003 to include several additional hospitals and countries (GRACE 2 ). Enrollment of GRACE and GRACE 2 ended in December 2007. Participating Canadian sites extended their data collection to December 2008 as the CANRACE using an identical study design. In total 57 hospitals across Canada participated in GRACE, GRACE 2 , and CANRACE. The present study consisted of all Canadian patients enrolled in these registries. The study was approved by local ethics review boards and informed consent was provided by participating patients.
We defined in-hospital lipid testing as measurement of the lipid profile, which included determination of low-density lipoprotein (LDL) cholesterol level. Use of statin therapy was recorded at 3 time points: before hospital admission, in hospital (before and 24 hours after admission), and after discharge (prescription). To explore temporal trends in use of lipid testing and statin therapy and to assess the impact of recent landmark trials on use of statins in ACS, we stratified the study population into 3 groups according to time of enrollment (1999 to 2004, 2005 to 2006, and 2007 to 2008). We used a longer interval for the first group to allow a comparable number of patients in each group because the number of participating centers and patient enrollment in the registries increased significantly with time. We compared use of lipid testing and statin therapy among these groups. To assess the impact of results of lipid testing on management, we stratified patients who had lipid testing into 3 groups (LDL cholesterol <100 mg/dl [<2.6 mmol/L], LDL cholesterol 100 to 130 mg/dl [2.6 to 3.4 mmol/L], LDL cholesterol >130 mg/dl [3.4 mmol/L]) based on guideline recommendations at time of enrollment.
Continuous variables are reported as medians with interquartile ranges and categorical variables as percentages. Comparisons were made using chi-square tests for categorical variables and Kruskal–Wallis test for continuous variables.
To characterize the relation among in-hospital lipid testing, in-hospital statin therapy, and time, a multivariable logistic regression analysis was performed with in-hospital statin therapy as the outcome variable. The model was adjusted for several patient and hospital factors that have been previously shown to be significantly associated using statin therapy. We used backward elimination (p >0.05) to arrive at a parsimonious model. Because patients admitted to the same hospital tend to be more similar, we used generalized estimating equations to account for clustering of patients within hospitals. We conducted a separate multivariable logistic regression analysis using in-hospital lipid testing as the dependent variable. To assess for survival bias, we performed a sensitivity analysis excluding patients who did not survive to hospital discharge. All statistical analyses were performed with SPSS 15.0 (SPSS, Inc., Chicago, Illinois), and a p value <0.05 (2-sided) denotes statistical significance.
Results
From January 1999 through December 2008, 14,015 patients with a final diagnosis of ACS were enrolled in these registries across Canada. We excluded patients who, according to the treating physician, had contraindications to statin therapy (n = 68). Of the 13,947 patients included in our cohort, 70.8% had lipid testing during admission, and 79.4% were treated with a statin during hospital admission. Final diagnoses were STEMI, NSTEMI, and UAP in 27.9%, 46.6%, and 25.5% of patients, respectively.
Table 1 lists baseline characteristics and clinical presentations of the study cohort stratified by in-hospital lipid testing and by in-hospital statin therapy. Overall, 53.7% of patients had a previous diagnosis of dyslipidemia and 40% of patients were on a statin before admission. In-hospital lipid testing was more common in younger patients and men. Patients who were already on statins were less likely to be tested, as were those with previous diabetes and hypertension. Patients with a cardiac history including angina, MI, previous revascularization, and heart failure were also less likely to have lipid testing. Patients who did not have lipid testing had higher GRACE risk scores. Lipid testing was more frequent in patients with a final diagnosis of STEMI and NSTEMI compared to patients diagnosed with UAP.
Variable | Overall (n = 13,947) | In-Hospital Lipid Testing | p Value | In-Hospital Statin Use | p Value | ||
---|---|---|---|---|---|---|---|
No (n = 4,079) | Yes (n = 9,868) | No (n = 2,803) | Yes (n = 11,069) | ||||
Age (years) ⁎ | 67 (57–77) | 70 (58–80) | 66 (56–76) | <0.001 | 72 (59–81) | 65 (56–76) | <0.001 |
Men | 66.6% | 61.9% | 68.5% | <0.001 | 59.4% | 68.4% | <0.001 |
Previous dyslipidemia | 53.7% | 53.1% | 53.9% | 0.349 | 36.2% | 58.2% | <0.001 |
Previous statin use | 40.0% | 43.6% | 38.4% | <0.001 | 16.8% | 45.8% | 0.001 |
Diabetes mellitus | 27.4% | 31.1% | 25.9% | <0.001 | 27.2% | 27.5% | 0.799 |
Hypertension | 60.4% | 62.8% | 59.4% | <0.001 | 60.8% | 60.3% | 0.627 |
Current smoker | 26.8% | 23.5% | 28.1% | <0.001 | 22.2% | 27.9% | <0.001 |
Angina pectoris | 43.1% | 48.4% | 40.9% | <0.001 | 42.2% | 46.2% | <0.001 |
Myocardial infarction | 32.6% | 38.1% | 30.3% | <0.001 | 32.0% | 32.8% | 0.431 |
Percutaneous coronary intervention | 17.6% | 19.7% | 16.8% | <0.001 | 11.9% | 19.1% | <0.001 |
Coronary bypass surgery | 12.3% | 14.3% | 11.4% | <0.001 | 9.2% | 13.1% | <0.001 |
Heart failure | 10.8% | 14.7% | 9.2% | <0.001 | 15.7% | 9.5% | <0.001 |
Transient ischemic attack/stroke | 9.2% | 11.7% | 8.1% | <0.001 | 10.8% | 8.8% | 0.001 |
Peripheral artery disease | 8.8% | 9.9% | 8.3% | 0.003 | 8.9% | 8.8% | 0.856 |
Clinical presentation | |||||||
Heart rate (beats/min) ⁎ | 78 (66–93) | 79 (67–94) | 78 (66–92) | <0.001 | 81 (68–98) | 77 (66–92) | <0.001 |
Systolic blood pressure (mm Hg) ⁎ | 143 (125–162) | 142 (123–160) | 144 (125–162) | <0.001 | 142 (122–160) | 144 (126–162) | <0.001 |
Positive cardiac biomarker | 47.9% | 46.7% | 48.4% | 0.064 | 44.7% | 48.7% | <0.001 |
ST-segment deviation | 46.2% | 44.8% | 46.8% | 0.026 | 46.5% | 46.1% | 0.703 |
Killip class | <0.001 | <0.001 | |||||
I | 83.6% | 77.8% | 85.9% | — | 74.0% | 86.0% | — |
II | 10.7% | 14.9% | 8.9% | — | 16.6% | 9.2% | — |
III | 5.4% | 6.5% | 4.9% | — | 8.6% | 4.6% | — |
IV | 0.4% | 0.8% | 0.2% | — | 0.9% | 0.3% | — |
Cardiac arrest | 1.5% | 2.4% | 1.1% | <0.001 | 3.2% | 1.0% | <0.001 |
Creatinine (μmol/L) ⁎ | 93 (78–112) | 94 (79–118) | 92 (78–110) | <0.001 | 96 (80–123) | 92 (78–110) | <0.001 |
GRACE risk score ⁎ | 127 (103–157) | 133 (107–166) | 125 (102–153) | <0.001 | 139 (108–176) | 124 (102–152) | <0.001 |
Final diagnosis | <0.001 | <0.001 | |||||
ST-segment elevation myocardial infarction | 27.9% | 23.7% | 29.6% | — | 25.9% | 28.4% | — |
Non–ST-segment elevation myocardial infarction | 46.6% | 44.9% | 47.3% | — | 43.2% | 47.4% | — |
Unstable angina pectoris | 25.5% | 31.4% | 23.1% | — | 30.9% | 24.2% | — |
⁎ Data are presented as median (twenty-fifth to seventy-fifth percentiles).
In-hospital statin therapy also was more common in younger patients and men. Previous statin use was much higher in those treated with in-hospital statins compared to those who were not. Median GRACE risk score was lower in patients who received in-hospital statins compared to those who did not. Patients with a final diagnosis of STEMI and NSTEMI were more likely to be treated with in-hospital statins compared to those with a diagnosis of UAP.
Table 2 presents in-hospital management stratified by lipid testing and in-hospital statin therapy. In-hospital lipid testing and in-hospital statin use were associated with increased use of evidence-based therapies including medications used within the first 24 hours and prescribed on discharge, and invasive procedures including coronary angiography and revascularization.
Variable | Overall (n = 13,947) | In-Hospital Lipid Testing | p Value | In-Hospital Statin Use | p Value | ||
---|---|---|---|---|---|---|---|
No (n = 4,079) | Yes (n = 9,868) | No (n = 2,803) | Yes (n = 11,069) | ||||
Medication use in first 24 hours | |||||||
Aspirin | 92% | 87.8% | 93.7% | <0.001 | 81.4% | 94.7% | <0.001 |
Clopidogrel | 65.7% | 60.0% | 68.0% | <0.001 | 44.4% | 70.4% | <0.001 |
Heparin | 87.2% | 80.5% | 89.9% | <0.001 | 79.9% | 89.0% | <0.001 |
Angiotensin-converting enzyme inhibitor | 54.9% | 50.7% | 56.6% | <0.001 | 37.1% | 59.3% | <0.001 |
β Blocker | 77.9% | 73.0% | 79.9% | <0.001 | 60.2% | 82.3% | <0.001 |
Thrombolytics | 12.8% | 9.9% | 14.0% | <0.001 | 11.6% | 13.1% | 0.03 |
In-hospital invasive management | |||||||
Coronary angiography | 60.4% | 50% | 64.7% | <0.001 | 41.4% | 65.2% | <0.001 |
Percutaneous coronary intervention | 34.1% | 31.0% | 35.3% | <0.001 | 21.1% | 37.3% | <0.001 |
Coronary bypass surgery | 3.3% | 2.3% | 3.7% | <0.001 | 2.8% | 3.4% | 0.13 |
Discharge therapies (n = 9,920) | |||||||
Aspirin | 86.5% | 80.8% | 88.9% | <0.001 | 75.6% | 89.2% | <0.001 |
Thienopyridines ⁎ | 60.5% | 55.2% | 62.7% | <0.001 | 39.2% | 65.6% | <0.001 |
Angiotensin-converting enzyme inhibitors | 61.9% | 57.1% | 63.8% | <0.001 | 48.7% | 65.0% | <0.001 |
β Blockers | 78.1% | 74.3% | 79.6% | <0.001 | 66.3% | 81.0% | <0.001 |
Statins | 79.9% | 72.9% | 82.8% | <0.001 | 6.3% | 93.7% | <0.001 |
Of the 40% of patients who were on statins before presentation, 91.5% were continued on statins while in hospital. Most patients who were treated with in-hospital statins (85.5%) were initiated on statins within 24 hours of admission. In patients who were discharged on a statin, 92.7% were on a statin during hospital admission and 79.3% were initiated on a statin within 24 hours of admission. Table 3 presents temporal trends of in-hospital lipid testing and statin therapy. There was a small but significant increase in rates of in-hospital lipid testing (p for trend = 0.003). We observed a significant increase in statin use over the 3 time periods, including rates of prior statin use, in-hospital statin use, and statin use on discharge (all p for trend <0.001).
Total | 1999–2004 (n = 3,625) | 2005–2006 (n = 5,089) | 2007–2008 (n = 5,232) | p Value for Trend | |
---|---|---|---|---|---|
In-hospital lipid-testing | 70.8% | 69.4% | 70.1% | 72.4% | 0.003 |
Statin therapy before admission | 40.0% | 35.6% | 42.0% | 41.0% | <0.001 |
In-hospital statin therapy | 79.8% | 70.0% | 81.9% | 84.5% | <0.001 |
Within first 24 hours | 68.2% | 55.0% | 71.5% | 74.1% | <0.001 |
After first 24 hours | 70.3% | 64.7% | 71.3% | 73.2% | <0.001 |
At discharge ⁎ | 79.9% | 71.1% | 82.2% | 83.6% | <0.001 |
In-hospital use of other lipid-modifying agents | 5.2% | 7.0% | 4.6% | 4.6% | <0.001 |
⁎ Data on discharge medications available for 9,920 patients only.
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