Discussion
In this retrospective observational cohort study, we found that the use of two high-intensity doses of atorvastatin (40mg vs. 80mg) post-ACS was associated with similar cardiovascular outcomes, including CVD-related death, non-fatal ACS, and non-fatal stroke at 1 month and 12 months post-discharge. In addition, the two high-intensity doses of atorvastatin resulted in similar safety outcomes. Since a high-intensity statin therapy, such as atorvastatin 40mg or 80mg, is recommended by clinical practice guidelines for secondary prevention post atherosclerotic CVD based on landmark trials that mainly evaluated the efficacy and safety of atorvastatin 80mg,1,2 it was hypothesized that atorvastatin 40mg would result in comparable CV benefit post-ACS when compared to the atorvastatin 80mg.
The cardiovascular benefit of high-intensity statin therapy was demonstrated in a meta-analysis of five randomized controlled trials evaluating more vs. less intensive statin therapy among a total of 39,612 individuals.13 The meta-analysis showed a significant reduction in the major adverse vascular events of 15% (95% CI 11–18; p <0.0001), non-fatal myocardial infarction (MI) of 13% (95% CI 7–19; p <0.0001), coronary revascularization of 19% (95% CI 15–24; p <0.0001), and ischemic stroke of 16% (95% CI 5–26; p=0.005) with the use of high-intensity statin. The benefit of atorvastatin 80mg post-ACS specifically was well established in the PROVE-IT and IDEAL trials.8,14 In the PROVE-IT trial, the use of atorvastatin 80mg compared to pravastatin 40mg over 2 years had resulted in a significant reduction in a composite endpoint of all-cause mortality, MI, UA requiring hospitalization, revascularization, and stroke (22.4% vs. 26.3, 95% CI 5-26; p=0.005).8 In the IDEAL trial, atorvastatin 80mg compared to simvastatin 20mg reduced non-fatal MI significantly (6% vs. 7.2%, HR = 0.83; 95% CI, 0.71-0.98; p=0.02) over a follow-up period of 4.8 years among patients with previous history of MI.14 Compared to the PROVE-IT and IDEAL trials, the present study reported a lower event rate of the CV outcomes, which might be explained by the shorter follow-up period of 12 months. Nevertheless, the current study demonstrated a novel and reassuring observation, that atorvastatin 40mg has similar CV benefits post-ACS in comparison to atorvastatin 80mg.
According to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) guidelines for dyslipidemia for secondary prevention of cardiovascular events among patients who have atherosclerotic CVD, a high-intensity statin is defined as a statin therapy that lowers LDL-C by ≥50%.2 In the current study, atorvastatin 80mg was significantly better in lowering LDL-C by ≥50% compared to atorvastatin 40mg which is consistent with the CURE-ACS trial that mainly aimed at evaluating the LDL-C lowering effects of atorvastatin 40mg versus 80mg and showed a greater reduction of LDL-C in the atorvastatin 80mg group compared to the 40mg group (27.5% vs 19.04%).11 Despite that the baseline LDL-C was significantly higher in the atorvastatin 80mg group (130 ± 44.7 vs. 110 ± 41.9 mg/dL ; p <0.001), both doses were able to reduce LDL-C to less than 70mg/dL, which is the target LDL-C for patients with very high risk of atherosclerotic CVD as per the 2018 ACC/AHA guidelines for dyslipidemia.2 However, the follow-up data of LDL-C was only available for 40% of the study patients, which might be explained by the fact that 2013 ACC/AHA guidelines for dyslipidemia for secondary prevention of cardiovascular events recommended using a high-intensity statin post-ACS regardless of LDL-C.1Therefore, this finding should be interpreted in the light of this limitation.
In addition to similar effectiveness between the two high-intensity doses of atorvastatin, this study demonstrated similar safety outcomes, including liver toxicity, myopathy, and rhabdomyolysis, with a very low event rate of < 1%, which is consistent with high-intensity statin landmark trials.8,10,14
In the present study, we further investigated the predictors of prescribing atorvastatin 80mg compared to 40mg as the rate of prescribing 80mg at our facility is low, which resulted in unbalanced study groups in terms of the number of the study participants. Upon conducting the screening of patients who were prescribed high-intensity atorvastatin doses at our facility during the study period, we found that atorvastatin 80mg to 40mg prescribing ratio was 1:19. The factors that were significantly associated with prescribing atorvastatin 80mg were STEMI as an index event, PCI as the method of treatment of the index event, and BMS implantation. These findings demonstrate the prescribing pattern of atorvastatin high-intensity doses at our facility, but do not present causality.
This study was a retrospective observational cohort study using real-world data that is susceptible to potential limitations. First, data were collected from electronic medical records retrospectively with the expectation of missing some important clinical information. Second, the effectiveness outcomes were adjusted for clinically significant patient and disease variables; however, there is a potential for other measured or unmeasured variables to influence the results. Third, the number of atorvastatin 40mg and 80mg users was relatively small, and the groups had an unequal number of participants due to the prescribing pattern of atorvastatin high-intensity doses at our facility, which might have affected the robustness of the analyses. Nevertheless, this retrospective observational cohort study aimed to answer a clinically important question that is faced by cardiologists in daily practice, and it could serve as a preliminary indicator for future prospective studies to assess the impact of atorvastatin 40mg post-ACS on cardiovascular outcomes.
In conclusion, the use of atorvastatin 40mg in comparison to atorvastatin 80mg after ACS had resulted in comparable effectiveness and safety outcomes over a follow-up period of 1 year. Therefore, following ACS, clinicians may use either high-intensity atorvastatin dose. However, larger studies with a longer follow-up period are warranted to confirm the findings of the present study.