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.