Assessing the Impact of Long-Term High-Dose Statin Treatment on Pericoronary Inflammation and Plaque Distribution-A Comprehensive Coronary CTA Follow-Up Study.

Computed tomography angiography (CTA) has validated the use of pericoronary adipose tissue (PCAT) attenuation as a credible indicator of coronary inflammation, playing a crucial role in coronary artery disease (CAD). This study aimed to evaluate the long-term effects of high-dose statins on PCAT attenuation at coronary lesion sites and changes in plaque distribution. Our prospective observational study included 52 patients (mean age 60.43) with chest pain, a low-to-intermediate likelihood of CAD, who had documented atheromatous plaque through CTA, performed approximately 1 year and 3 years after inclusion. We utilized the advanced features of the CaRi-Heart® and syngo.via Frontier® systems to assess coronary plaques and changes in PCAT attenuation. The investigation of changes in plaque morphology revealed significant alterations. Notably, in mixed plaques, calcified portions increased (p < 0.0001), while non-calcified plaque volume (NCPV) decreased (p = 0.0209). PCAT attenuation generally decreased after one year and remained low, indicating reduced inflammation in the following arteries: left anterior descending artery (LAD) (p = 0.0142), left circumflex artery (LCX) (p = 0.0513), and right coronary artery (RCA) (p = 0.1249). The CaRi-Heart® risk also decreased significantly (p = 0.0041). Linear regression analysis demonstrated a correlation between increased PCAT attenuation and higher volumes of NCPV (p < 0.0001, r = 0.3032) and lipid-rich plaque volume (p < 0.0001, r = 0.3281). Our study provides evidence that high-dose statin therapy significantly reduces CAD risk factors, inflammation, and plaque vulnerability, as evidenced by the notable decrease in PCAT attenuation, a critical indicator of plaque progression.

Impact of high-dose statin on cardiovascular outcomes in real-world patients with ST-elevation acute myocardial infarction.

Little is known about the impact of a high-dose statin on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real-world Japanese patients. Between July 2011 and June 2017, 1110 consecutive STEMI patients underwent primary percutaneous coronary intervention at our hospital and were discharged. A high-dose statin was administered in 117 patients (10.5%) and non-high-dose statin was administered in 947 patients (85.3%). The low-density lipoprotein cholesterol level was significantly higher in the high-dose statin group at admission (129.8 ± 44.9 vs. 110.4 ± 32.7, p < 0.0001), but the levels were not significantly different at follow-up (86.7 ± 25.7 vs. 85.0 ± 25.0, p = 0.52). The cumulative 2-year incidence of a composite of cardiac death, myocardial infarction, ischemic stroke, and any unplanned coronary revascularization was significantly lower in the high-dose statin group (6.2% vs. 16.9%, log-rank p = 0.004). Propensity score matched analysis indicated similar results. Among the types of coronary revascularization, a high-dose statin was significantly correlated with a lower rate of de novo lesion revascularization (hazard ratio 0.31; 95% confidence interval 0.08-0.83; p = 0.02). The results of our analyses indicate that administration of a high-dose statin may result in better cardiovascular outcomes after STEMI mainly by reducing the rate of revascularization for de novo lesions regardless of the achieved low-density lipoprotein cholesterol level in real-world patients.

Rationale and Design of Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) Trial.

Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However, such evidence has not yet been fully established in Asian populations, including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD.REAL-CAD is a prospective, multicenter, randomized, open-label, blinded-endpoint, physician-initiated phase 4 trial in Japan. The study will recruit up to 12,600 patients with stable CAD. Patients are assigned to receive either pitavastatin 1 mg/day or pitavastatin 4 mg/day. LDL-C levels are expected to reach approximate mean values of 100 mg/dL in the low-dose pitavastatin group and 80 mg/dL in the high-dose group. The primary endpoint is the time to occurrence of a major CV event, including CV death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization during an average of 5 years. The large number of patients and the long follow-up period in the REAL-CAD study should ensure that there is adequate power to definitively determine if reducing LDL-C levels to approximately 80 mg/dL by high-dose statin can provide additional clinical benefit.After the study is completed, we will have categorical evidence on the optimal statin dose and target LDL-C level for secondary prevention in Japanese patients.

High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings.

Efficacy of single high-dose statin prior to percutaneous coronary intervention in acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: The impacts of single high-dose statin preloading in patients undergoing percutaneous coronary intervention (PCI) have not been fully examined. This study aims to evaluate post-procedure impacts of single high-dose statin pretreatment with acute coronary syndrome (ACS). METHODS: The meta-analysis reviewed Cochrane, PubMed, and Medline databases for studies comparing single high-dose atorvastatin or rosuvastatin to placebo in ACS patients undergoing PCI. The primary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), all-cause mortality, and target vessel revascularization (TVR) at three months. Secondary endpoints examined were the TIMI flow grade 3 and left ventricular ejection fraction (LVEF). RESULTS: Comprehensive analysis was conducted on fifteen RCTs, encompassing a total of 6,207 patients (3090 vs 3117 patients). The pooled results demonstrated that a single high-dose of statin administered prior to PCI led to a significant decrease in the incidence of MACE at three months post-PCI compared to the control group (OR 0.50, 95%CI 0.35-0.71, p = 0.0001). The occurrence of MI (OR 0.57, 95%CI 0.42-0.77, p = 0.0002), all-cause mortality (OR 0.56, 95%CI 0.39-0.81, p = 0.0002), and TVR (OR 0.56, 95%CI 0.35-0.92, p = 0.02) was significantly lower in the statin single high-dose group compared to the control group. No significant effects on TIMI flow grade 3 (OR 1.20, 95%CI 0.94-1.53, p = 0.14) or left ventricular ejection fraction (OR 2.19, 95%CI - 0.97 to 5.34, p = 0.17) were observed. Subgroup analysis demonstrated reduced incidence of MACE with a single dose of 80 mg atorvastatin (OR 0.66, 95%CI 0.54-0.81, p < 0.0001) and 40 mg rosuvastatin (OR 0.19, 95%CI 0.07-0.54, p = 0.002). CONCLUSIONS: Single high-dose statin before PCI in patients with ACS significantly reduces MACE, MI, all-cause mortality, and TVR three months post-PCI.

Lipid-Lowering Treatment and the Lipid Goals Attainment in Patients with a Very High Cardiovascular Risk.

Hypercholesterolemia is the main cardiovascular (CV) risk factor with a large body of evidence. Our aim was to assess the achievement of the main therapeutic goal of Low-Density Lipoprotein Cholesterol (LDL-C) in patients with a very high CV risk and a high-dose statin therapy. The study group consisted of 1413 consecutive patients hospitalised at the Upper-Silesian Medical Centre in Katowice due to acute myocardial infarction (AMI) treated with atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg. The lipid profile was performed on admission and within 12 months after AMI. The main therapeutic goal was defined as LDL-C < 55 mg%. The study group (n = 1413) included 979 males (69.3%) with arterial hypertension (83.3%), diabetes (33.5%), peripheral artery disease (13.6%) and nicotinism (46.2%). In the study group, only 61 patients (4.3%) were additionally taking ezetimibe. During hospitalisation, the primary LDL-C goal was found in only 186 patients (13.2%). Subsequently, a follow-up lipidogram within 12 months was performed in 652 patients (46%), and the therapeutic goal was achieved in 255 patients (39%). There were 258 (18.26%) patients who died within 12 months after myocardial infarction. The lowest mortality rate was found in the subgroup of patients with LDL-C < 55 mg% during follow-up (11.02%). The primary lipid goal attainment among patients with a high-dose statin and a very high CV risk is low and far from the expected rate. Patients hospitalised for AMI should be given a combination of statin and ezetimibe more frequently. Low LDL-C levels measured at follow-up predict a lower risk of death at 12-month follow-up in a large group of patients.

Low-to-moderate dose statins improve the functional outcome of acute ischemic stroke with conventional medication treatment.

Background: Low-to-moderate dose statins (LMDSs) are more commonly used among Asian acute ischemic stroke (AIS) patients in clinical practice. However, the correlation between the LMDS use and prognosis has not been evaluated in AIS patients with conventional medication treatment alone. This study aimed to investigate the influence of LMDS on the prognosis of AIS patients and how prognosis and potential prognostic factors interact with different statin doses. Methods: This retrospective cohort study included AIS patients who were admitted within 7 days after symptom onset and received conventional medication treatment alone from November 2019 to November 2020 in the Neurology, Department of West China Hospital, Sichuan University. From a total of 782 initial patients, a final cohort of 327 patients was included in the study. These patients were divided into three groups based on statin doses: non-statin (48 patients), LMDS (152 patients), and high-dose statin (HDS) (127 patients). The follow-up period was 3 months after the onset of stroke and the primary outcome was defined as a modified Rankin scale (mRS) score of 0 to 2 at 3 months, secondary outcomes were hemorrhagic transformation (HT) and death within 3 months. Stratified analysis was also conducted to test the robustness of the relationship between the use of different statin doses and functional outcomes in various subgroups. Results: Compared with non-statin therapy, both LMDS therapy and HDS therapy were associated with good functional outcomes [odds ratio (OR) =3.68, 95% confidence interval (CI): 1.13-12.01, P=0.0309; OR =3.45, 95% CI: 1.06-11.26, P=0.0402, respectively] and a lower risk of HT (OR =0.30, 95% CI: 0.11-0.86, P=0.0253; OR =0.36, 95% CI: 0.13-0.99, P=0.0488, respectively). However, there was no significant difference in all-cause death within 3 months among the three groups (OR =0.84, 95% CI: 0.29-2.46, P=0.7468; OR =0.76, 95% CI: 0.26-2.22, P=0.6104). Additionally, no significant differences were observed between LMDS therapy and HDS therapy regarding good functional outcomes at 3 months (OR =0.94, 95% CI: 0.50-1.77, P=0.8411) and the occurrence of HT (OR =1.19, 95% CI: 0.47-3.02, P=0.7093). The results of the relationship between different statin doses and 3-month good functional outcome were consistent after interaction tests. Conclusions: Our findings provide evidence for the benefit and safety of LMDS therapy in AIS patients with medication treatment alone. LMDS therapy is associated with favorable impacts on 3-month functional outcomes and a reduced risk of HT compared to non-statin therapy. There were no significant differences in achieving 3-month good functional outcome, the risk of HT or death within 3 months were observed between LMDS and HDS therapy in our study. Further studies with prospective design and larger sample sizes are necessary to validate our results.

Comorbidities Associated With Residual Cardiovascular Risk in Patients With Chronic Coronary Syndrome Receiving Statin Therapy　- Subanalysis of the REAL-CAD Trial.

Background: Even with high-dose statin therapy, residual cardiovascular event risks remain in patients with chronic coronary syndrome (CCS). Thus, future treatment targets need to be elucidated. This study determined the factors associated with residual cardiovascular risk in patients with CCS treated with high-dose statins. Methods and Results: This study was a subanalysis of the REAL-CAD study. This study enrolled 5,540 patients with CCS receiving 4 mg/day pitavastatin and assessed the impacts of 3 representative risk factors (i.e., blood pressure, glucose level, and renal function), alone or in combination, on clinical outcomes. Each risk factor was classified according to its severity. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization. After adjusting for the effects of confounders, a significantly worse prognosis was observed in the group with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 (hazard ratio [HR] 1.36; 95% confidence interval 1.03-1.80; P=0.028). No other factors or combinations were associated with the primary endpoint. An eGFR ≤60 mL/min/1.73 m2 was also associated with cardiac (HR 2.38; P=0.004) and all-cause (HR 1.51; P=0.032) death. Conclusions: Insufficient renal function was associated with a worse prognosis in patients with CCS undergoing high-dose statin therapy, suggesting that renal function is the next target for reducing the risk of residual cardiovascular events.

Significant reduction in the LDL cholesterol increases the risk of intracerebral hemorrhage: a systematic review and meta-analysis of 33 randomized controlled trials.

The dose-dependent pleiotropic effects of statin therapy may have unwanted side effects such as increasing the risk of intracerebral hemorrhage (ICH). The relationships among statin therapy, LDL-cholesterol levels, and ICH risk remain controversial. Here, we conduct a systematic review and meta-analysis of dose-dependent statin therapy and ICH risk. Eligible articles were identified by searching MEDLINE from inception up to December 1, 2018. Reference lists of previous meta-analyses were manually searched to retrieve all relevant publications. Statin doses were allocated into one of two groups according to the observed reduction of LDL cholesterol: doses that lowered LDL-cholesterol levels ≥35% were regarded as high-dose statin therapy, whereas those that lowered LDL-cholesterol levels <35% were regarded as low-dose statin therapy. We retrieved 33 studies involving 203,305 subjects. The pooled analysis indicated that high-dose statin treatment significantly increased the risk of ICH [relative risk (RR), 1.35; 95% confidence interval (CI), 1.08-1.68] and reduced the risk of all stroke (RR, 0.85; 95% CI, 0.78-0.92), ischemic stroke (RR, 0.79; 95% CI, 0.72-0.87), and all-cause mortality (RR, 0.94; 95% CI, 0.90-0.98). The analyses did not detect any association between low-dose statin treatment and ICH (RR, 1.05; 95% CI, 0.88-1.25). Low-dose statin therapy significantly reduced the incidence of all stroke (RR, 0.84; 95% CI, 0.79-0.89), ischemic stroke (RR, 0.81; 95% CI, 0.76-0.86), and all-cause mortality (RR, 0.94; 95% CI, 0.92-0.97). Our data indicate that low-dose statin therapy is a safe and effective ICH treatment, whereas high-dose statin therapy is associated with increased ICH risk. Hence, our meta-analysis suggests that the dose-dependent pleiotropic effects of statin therapy are related to the measured reduction in LDL cholesterol.

Effects of High Dose of Atorvastatin for Preventing Periprocedural Ischemic Brain Damage in Patients Undergoing Carotid Artery Stenting (PICAS) in China: A Randomized Controlled Clinical Trial.

Background: Research conducted in Western countries has suggested that high-dose statin therapy can lead to the regression of carotid atherosclerotic plaques and can reduce periprocedural ischemic complication rates in individuals undergoing carotid artery stenting (CAS). However, whether this same therapeutic approach is of value in patients of Chinese ethnicity is not as well-established. Methods: This is a single-center, prospective, parallel-controlled, intervention-based efficacy study that will enroll a total of 130 Chinese patients with cervical carotid stenosis who are scheduled to undergo CAS. These patients will be randomly divided into a routine treatment group and a high-dose atorvastatin group. Individuals in the routine treatment group will be administered standard of care 20 mg/day atorvastatin treatment. Individuals in the high-dose atorvastatin group will be administered 80 mg/day atorvastatin for 3 days prior to and following CAS. The primary outcome of this study will be the cumulative incidence of new cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging (DW-MRI) within 5 days following CAS, and of transient ischemic attacks (TIAs) or ischemic stroke within 30 days after CAS. Discussion: This study is the first to assess whether high-dose atorvastatin treatment is capable of reducing the incidence of perioperative cerebral ischemic injury in patients of Chinese ethnicity undergoing CAS. These results will offer evidence regarding which statin treatment regimens are more appropriate when treating Chinese patients undergoing CAS in an effort to minimize their risk of any perioperative cerebral ischemic injury. Trial Registration: ClinicalTrials.gov NCT03079115; registered March 14, 2017.

Effect of sarpogrelate and high-dose statin on the reduction of coronary spasm in vasospastic angina: A two by two factorial, pilot randomized study.

BACKGROUND: Vasospastic angina (VSA) is characterized by coronary spasm, which can be aggravated by vasoactive substances such as serotonin. Hypothesis Sarpogrelate, a selective serotonin receptor antagonist, and high-dose statin have some effects on the reduction of coronary spasm in patients with VSA. METHODS: We recruited 100 patients with angiographically confirmed VSA, and randomly assigned them into four groups: sarpogrelate with high-dose statin (Group A, n = 25), sarpogrelate with low-dose or no statin (Group B, n = 25), placebo with high-dose statin (Group C, n = 25), and placebo with low-dose or no statin (Group D, n = 25). The primary endpoint was the remission of coronary spasm on 1-year follow-up provocation test. RESULTS: The most common site of coronary spasm was left anterior descending artery (42%). Most patients (96%) took calcium channel blockers, and 46% were treated with vasodilators. Overall, 40% of patients reported no chest pain at 1 year, and 23% showed complete remission of coronary spasm on 1-year follow-up provocation test. No difference was observed in symptomatic and angiographically complete remission rate between the sarpogrelate and the placebo group. Although the apolipoprotein B level at the 1-year follow-up was significantly lower in the high-dose statin group, symptomatic and angiographic outcomes were not different according to statin intensity. Distal thrombolysis in myocardial infarction (TIMI) flow on initial provocation test was independently associated with angiographically complete remission. CONCLUSIONS: Sarpogrelate or high-dose statin did not significantly improve the angiographic remission rate in patients with VSA. Distal TIMI flow on initial provocation test could predict the complete remission of coronary spasm at follow-up.

Renal impact of high-loading-dose statin pre-cardiac catheterization in patients with chronic kidney disease and long-term statin use.

Previous studies have reported that short-term statin loading effectively protects statin-naive patients with mild renal insufficiency from contrast-induced acute kidney injury (CI-AKI). The aim of the present study was to determine whether patients with more advanced chronic kidney disease (CKD) and long-term statin therapy also benefit from high-loading statin pretreatment. A total of 256 consecutive patients with moderate-to-severe CKD receiving long-term statin therapy and undergoing percutaneous coronary intervention (PCI) or coronary artery angiography (CAG) were divided into the statin-loading group (n=34) and the no statin-loading group (n=222), depending on whether the respective patient received high-dose statin within 24 h prior to the intervention. The primary endpoint was the percent change in serum creatinine (SCr) levels. Additional endpoints included absolute change in SCr levels, estimated glomerular filtration rate (eGFR) at 48-72 h after contrast exposure, incidence rate of CI-AKI and composite in-hospital adverse events. The mean SCr decreased from baseline in either of the two groups, and the differences in the percent (P=0.930) and absolute change (P=0.990) in SCr levels were not significant between the two groups. Furthermore, no significant difference in the post-procedural eGFR was observed between the two groups. The incidence rates of CI-AKI (2.9 vs. 4.1%, P>0.999) and in-hospital adverse events (0.0 vs. 3.6%, P=0.602) were also similar between the two groups. Stratified analyses were then performed, which yielded results consistent with the above. Multiple linear regression indicated that the baseline eGFR value and current smoking status were independent factors affecting the post-procedural eGFR value, while high-dose statin loading was not. Therefore, statin reloading prior to intervention may not provide any further renal protection or decrease the occurrence of in-hospital adverse events in patients with moderate-to-severe CKD receiving long-term statin therapy, which warrants validation in prospective trials.

Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study.

BACKGROUND: Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. OBJECTIVES: This study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy. METHODS: In a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion. All subjects received 40 mg of rosuvastatin daily for 8 to 12 weeks, when the nonculprit lesion was reimaged and intervention performed. Blood samples were drawn at both times to assess CEC and transcriptomic profile in PBMC. RESULTS: Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 µm, which increased to 108.6 ± 39.6 µm at follow-up, and baseline CEC was 0.81 ± 0.14, which increased at follow-up to 0.84 ± 0.14 (p = 0.003). Thin-cap fibroatheroma prevalence decreased from 20.0% to 7.1% (p = 0.003). Changes in FCT were independently associated with CEC increase by multivariate analysis (ß: 0.30; p = 0.01). PBMC microarray analysis detected 117 genes that were differentially expressed at follow-up compared to baseline, including genes playing key roles in cholesterol synthesis (SQLE), regulation of fatty acids unsaturation (FADS1), cellular cholesterol uptake (LDLR), efflux (ABCA1 and ABCG1), and inflammation (DHCR24). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable FCT and CEC changes. CONCLUSIONS: The study demonstrated an independent association between fibrous cap thickening and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients taking intensive statin therapy. Furthermore, the significant perturbations in PBMC transcriptome may help determine the beneficial effects of statin on plaque stabilization. (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering [YELLOW II]; NCT01837823).

Longitudinal treatment patterns among US patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia initiating lipid-lowering pharmacotherapy.

BACKGROUND: The most recent American College of Cardiology-American Heart Association guidelines recommend high-dose statin therapy for most patients with confirmed atherosclerotic cardiovascular disease (ASCVD) and patients with high cardiovascular risk. There is limited information regarding long-term treatment patterns among these patients. OBJECTIVE: To examine longitudinal treatment modifications in patients with ASCVD or familial hypercholesterolemia (FH). METHODS: This retrospective analysis of administrative claims data identified patients initiating statin or ezetimibe therapy between January 1, 2007, and December 31, 2012, who had evidence of ASCVD or FH. Patients were followed for up to 3 years and up to 4 treatment episodes. After initial treatment, subsequent treatment episodes began on the date of a treatment modification, which included discontinuation, statin dose change, switching, and augmentation. RESULTS: A total of 92,621 patients (mean age 64.7 years, 57.3% male) were identified; 91,740 had ASCVD, 937 had FH (56 had both). Most ASCVD (89.6%) and FH (85.8%) patients initiated on statin monotherapy. The most common treatment modification in the first treatment episode was discontinuation (ASCVD: 42.0%; FH: 58.4%); among patients who discontinued, most reinitiated therapy (70.5% of ASCVD, 76.8% of FH). Most ASCVD (68.2%) and FH (71.1%) patients initiated on moderate-dose statins; statin dose increase occurred in 10.3% of ASCVD and 18.5% of FH patients in the first episode. CONCLUSION: Among patients with high cardiovascular risk, most initiated on moderate-dose statins with infrequent uptitration. In light of the recent American College of Cardiology-American Heart Association guidelines, statin initiation practices will need to change to ensure appropriate therapy for high-risk patients.

High-dose statin therapy with rosuvastatin reduces small dense LDL and MDA-LDL: The Standard versus high-dose therApy with Rosuvastatin for lipiD lowering (SARD) trial.

BACKGROUND: Cardiovascular events (CV) continue to occur due to residual risks in high-risk patients in spite of substantial reductions in the low-density lipoprotein cholesterol (LDL) with statins. It has been reported that the small-dense LDL (sd-LDL) components of high atherogenic particles are associated with an increased risk of CV, more than large buoyant LDL. However, there are few reports regarding the effects of high-dose statin therapy in improving atherogenic lipoproteins. METHODS AND RESULTS: In this prospective, randomized, open-label, multicenter study, a total of 111 high-risk patients were randomly assigned to two groups. In the high-dose therapy group, 58 patients were administered 5mg of rosuvastatin per day for four weeks, after which the dose was titrated to 10mg for the following eight weeks. In the low-dose therapy group, 53 patients were given 2.5mg for 12 weeks. We evaluated the lipid profiles, including the levels of sd-LDL, malondialdehyde-modified LDL-cholesterol (C) (MDA-LDL) as oxidized-LDL, and remnant-like particle-cholesterol. The LDL-C, non-high-density lipoprotein (HDL), and LDL-C/HDL-C ratio were decreased in the high-dose therapy group (p<0.01). Moreover, the sd-LDL and MDA-LDL levels were significantly reduced in the high-dose therapy group (p<0.05). There were no serious adverse events in either group. CONCLUSIONS: High-dose statin therapy significantly reduced the sd-LDL and MDA-LDL components of atherosclerotic lipoproteins without adverse events in comparison with low-dose statin therapy.