High-Potency Statin and Ezetimibe Use and Mortality in AMI
In total, 9597 patients (57% male, mean age of 65±13 years) matched study criteria: 6990 (72.8%) were identified to be in the simvastatin monotherapy group; 1883 (19.6%) had an initial prescription for simvastatin, but were switched during follow-up to rosuvastatin or atorvastatin and included in the high-potency statin group; and 724 (7.5%) patients were on a combination of ezetimibe in addition to statin and were identified as the ezetimibe/statin combination group. The mean dose of simvastatin during follow-up in the simvastatin monotherapy group was 35±10 mg. The mean doses of high-potency statins were 12±6 mg for rosuvastatin and 30±22 mg for atorvastatin. In the ezetimibe/statin combination group, the mean dose of ezetimibe was 10±0 mg, simvastatin was 36±13 mg, atorvastatin was 35±23 mg and rosuvastatin was 13±7 mg.
The patients in the ezetimibe/statin combination group were slightly younger and were also more likely to be smokers (Table 1). The high-potency statin group had lower baseline blood pressure compared with the simvastatin monotherapy and ezetimibe/statin combination groups.
Lipid levels for baseline as well as following lipid-lowering therapy were only available in a proportion of patients. As patients do not always have available total cholesterol, LDL-C and HDL levels at the same time, there were different proportions of patients having lipid levels for total cholesterol, LDL-C and HDL at baseline and following lipid-lowering therapy (Table 2). Baseline total cholesterol was higher in the high-potency statin and ezetimibe/statin combination groups compared with the simvastatin monotherapy group (Table 2). There was a decrease in total cholesterol and LDL-C in all three groups with significantly greater percentage decrease in these measures in the high-potency statin group and the ezetimibe/statin combination group compared with the simvastatin monotherapy group (Table 2). Because of the higher baseline total cholesterol levels, the best achieved total cholesterol levels were not lower in the high-potency statin and ezetimibe/statin combination groups (Table 2).
During a mean follow-up of 3.2 years, there were 1134 (12%) deaths. In the multivariate proportional hazards model, the adjusted HR for the high-potency statin group was 0.72 (95% CI 0.59 to 0.88, p<0.001), and for the ezetimibe/statin combination group, the adjusted HR was 0.96 (95% CI 0.64 to 1.43, p<0.85). The proportional hazards model is shown in Table 3.
A similar result was also obtained in the propensity score analysis with an adjusted HR of 0.67 (95% CI 0.54 to 0.81, p<0.001) for high-potency statin use and an adjusted HR of 0.93 (95% CI 0.62 to 1.38, p<0.717) for ezetimibe use. In the subgroup analysis of 2787 patients with complete data for GFR, cholesterol and blood pressure, the HR for ezetimibe use and high-potency statin use were 1.03 (95% CI 0.47 to 2.23, p=0.943) and 0.79 (95% CI 0.55 to 1.131, p=0.19), respectively.
Results
Patient Characteristics
In total, 9597 patients (57% male, mean age of 65±13 years) matched study criteria: 6990 (72.8%) were identified to be in the simvastatin monotherapy group; 1883 (19.6%) had an initial prescription for simvastatin, but were switched during follow-up to rosuvastatin or atorvastatin and included in the high-potency statin group; and 724 (7.5%) patients were on a combination of ezetimibe in addition to statin and were identified as the ezetimibe/statin combination group. The mean dose of simvastatin during follow-up in the simvastatin monotherapy group was 35±10 mg. The mean doses of high-potency statins were 12±6 mg for rosuvastatin and 30±22 mg for atorvastatin. In the ezetimibe/statin combination group, the mean dose of ezetimibe was 10±0 mg, simvastatin was 36±13 mg, atorvastatin was 35±23 mg and rosuvastatin was 13±7 mg.
The patients in the ezetimibe/statin combination group were slightly younger and were also more likely to be smokers (Table 1). The high-potency statin group had lower baseline blood pressure compared with the simvastatin monotherapy and ezetimibe/statin combination groups.
Lipid Levels
Lipid levels for baseline as well as following lipid-lowering therapy were only available in a proportion of patients. As patients do not always have available total cholesterol, LDL-C and HDL levels at the same time, there were different proportions of patients having lipid levels for total cholesterol, LDL-C and HDL at baseline and following lipid-lowering therapy (Table 2). Baseline total cholesterol was higher in the high-potency statin and ezetimibe/statin combination groups compared with the simvastatin monotherapy group (Table 2). There was a decrease in total cholesterol and LDL-C in all three groups with significantly greater percentage decrease in these measures in the high-potency statin group and the ezetimibe/statin combination group compared with the simvastatin monotherapy group (Table 2). Because of the higher baseline total cholesterol levels, the best achieved total cholesterol levels were not lower in the high-potency statin and ezetimibe/statin combination groups (Table 2).
Outcomes
During a mean follow-up of 3.2 years, there were 1134 (12%) deaths. In the multivariate proportional hazards model, the adjusted HR for the high-potency statin group was 0.72 (95% CI 0.59 to 0.88, p<0.001), and for the ezetimibe/statin combination group, the adjusted HR was 0.96 (95% CI 0.64 to 1.43, p<0.85). The proportional hazards model is shown in Table 3.
A similar result was also obtained in the propensity score analysis with an adjusted HR of 0.67 (95% CI 0.54 to 0.81, p<0.001) for high-potency statin use and an adjusted HR of 0.93 (95% CI 0.62 to 1.38, p<0.717) for ezetimibe use. In the subgroup analysis of 2787 patients with complete data for GFR, cholesterol and blood pressure, the HR for ezetimibe use and high-potency statin use were 1.03 (95% CI 0.47 to 2.23, p=0.943) and 0.79 (95% CI 0.55 to 1.131, p=0.19), respectively.
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