Use Of High-intensity Statin Therapy Research Articles

Coronary and Extra-coronary Subclinical Atherosclerosis to Guide Lipid-Lowering Therapy.

To discuss and review the technical considerations, fundamentals, and guideline-based indications for coronary artery calcium scoring, and the use of other non-invasive imaging modalities, such as extra-coronary calcification in cardiovascular risk prediction. The most robust evidence for the use of CAC scoring is in select individuals, 40-75 years of age, at borderline to intermediate 10-year ASCVD risk. Recent US recommendations support the use of CAC scoring in varying clinical scenarios. First, in adults with very high CAC scores (CAC ≥ 1000), the use of high-intensity statin therapy and, if necessary, guideline-based add-on LDL-C lowering therapies (ezetimibe, PCSK9-inhibitors) to achieve a ≥ 50% reduction in LDL-C and optimally an LDL-C < 70 mg/dL is recommended. In patients with a CAC score ≥ 100 at low risk of bleeding, the benefits of aspirin use may outweigh the risk of bleeding. Other applications of CAC scoring include risk estimation on non-contrast CT scans of the chest, risk prediction in younger patients (< 40 years of age), its value as a gatekeeper for the decision to perform nuclear stress testing, and to aid in risk stratification in patients presenting with low-risk chest pain. There is a correlation between extra-coronary calcification (e.g., breast arterial calcification, aortic calcification, and aortic valve calcification) and incident ASCVD events. However, its role in informing lipid management remains unclear. Identification of coronary calcium in selected patients is the single best non-invasive imaging modality to identify future ASCVD risk and inform lipid-lowering therapy decision-making.

1021-P: Targeting Lower LDL Levels in Patients with Diabetes and ASCVD through a Novel Healthy Heart Program

The US prevalence of ASCVD with DM in the elderly has been reported to be 50%. This population is at significant risk for future CV complications. (1) Aggressive management of dyslipidemia in the primary care setting should be a central focus to reduce associated morbidity and mortality. (2) Current US LDL targets for pts with DM are &amp;lt; 70 mg/dl. Recent ESC/EAS Guidelines in pts with DM and ASCVD, defined as a very high risk (VHR) population, target LDL levels at &amp;lt;55 mg/dl. (3) This study evaluates the impact of a protocol driven program, Healthy Heart (HH), in achieving lower LDL levels in elderly Medicare Advantage pts with DM and ASCVD in the primary care setting. The HH program is a pre-defined intervention protocol administered by specially trained APRNs in primary care offices, with cardiology oversight. Continuity with PCP directed care was maintained. At each visit, ASCVD risk factors were measured and managed along with recommended lifestyle modification. In the first year, 421 pts referred to HH had DM with established ASCVD. Baseline and final LDL values along with high intensity statin (HIS) use are reported. Demographics: Mean age 75+/-5.9 YO, 69% F, 84% Hispanic/Latino, &amp;lt;1% AA, BMI 30.0+/-5.3 kg/m², previous CABG 38%, CHF 24%, Carotid AD 23%, and prior stroke/TIA 3%. Mean time between baseline and final LDL was 320+/-107 days. The average number of HH visits was 3.5+/-1.7. Results: At baseline, 12.5% of the cohort had an LDL of &amp;lt;70 mg/dl, significantly improving to 55.1% after intervention. For the lower LDL target of &amp;lt;55 mg/dl, 10.6% of the cohort were at target improving to 29.2%, the use of HIS therapy improved from 40.3% at baseline to 84.3%. All findings were significant (P&amp;lt; 0.0001). Conclusion: Using a pre-defined protocol administered by APRNs in a primary care setting significantly improved the percentage of VHR patients achieving LDL targets of &amp;lt;70 and &amp;lt;55 mg/dl. The use of HIS more than doubled. Additional study to evaluate clinical outcomes is warranted. Disclosure E.Antunez: None. R.E.Kenney: None. R.Aguilar: None. V.Mccloskey: None. J.Rivera: None.

Prevalent use of high-intensity statin therapy and LDL-C target attainment among PAD patients undergoing angioplasty.

Background: The global burden of peripheral arterial disease (PAD) is substantial. Reducing the major modifiable risk factors for noncommunicable disease, including dyslipidaemia, represents a public health priority. Aim is to evaluate the prevalent adequate use of lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) attainment among patients with PAD of the lower extremities undergoing percutaneous transluminal angioplasty. Patients and methods: We screened PAD patients treated at the University Hospital Zurich (January 2012-December 2018). We excluded patients <18 years, without classifiable severity of PAD, or with missing LDL-C or medication data. In this cross-sectional study, we studied the prevalent LLT use and LDL-C values in target according to the most recent European guidelines. Available clinical data included demographic information, lipid profile, type and dose of LLT, characteristics of the artery obstruction and angioplasty. Results: A total of 2,148 angioplasties were performed in 956 patients: 614 (64%) were men; the mean age was 70.6 (SD 11.4) years. A total of 608 (64%) had a non-critical PAD (Fontaine stage I-IIb), whereas the remaining had a critical limb ischemia or a diabetic foot syndrome. Their median LDL-C value was 2.00 (Q1-Q3: 1.50-2.60) mmol/L. In accordance to the 2016 and 2019 European Society of Cardiology guidelines, the LDL-C target of 1.8 and 1.4 mmol/L was not reached in 63% (n=599) and in 79% (n=760) of patients, respectively. Only 41% (n=390) of patients were on high-intensity statin therapy. Conclusions: The attainment of LDL-C targets, as recommended by current European guidelines, and the use of high-intensity LLT were unsatisfactory in the majority of PAD patients.

DA VINCI study: Change in approach to cholesterol management will be needed to reduce the implementation gap between guidelines and clinical practice in Europe

DA VINCI study: Change in approach to cholesterol management will be needed to reduce the implementation gap between guidelines and clinical practice in Europe

Role of Lipid-Lowering Therapy in Low-Density Lipoprotein Cholesterol Goal Attainment: Focus on Patients With Acute Coronary Syndrome.

:Dyslipidemia is a major risk factor for cardiovascular (CV) disease, which is the leading cause of death globally. Acute coronary syndrome (ACS) is a common cause of death, accounting for nearly half of the global burden of CV mortality. Epidemiologic studies have identified low-density lipoprotein cholesterol (LDL-C) as an independent CV risk factor, and this is now the primary target for initiating and adjusting lipid-lowering therapies in most current guidelines. Evidence from pivotal studies supports the use of high-intensity statin therapy and a lower level for optimal LDL-C in secondary prevention of atherosclerotic CV disease, especially in patients with ACS undergoing percutaneous coronary intervention. However, current research has identified a gap between the target LDL-C goal attainment and target LDL-C levels recommended by the guidelines. Statins have proven benefits in the management of CV disease and are the cornerstone of lipid-lowering management in patients with ACS. Recent randomized controlled trials have also demonstrated the benefits of cholesterol absorption inhibitors and proprotein convertase subtilisin/kexin type 9 inhibitors. This review summarizes the current evidence for LDL-lowering therapy in patients with ACS, with an emphasis on the importance of LDL-C goal attainment, rapid LDL-C lowering, and duration of LDL-C–lowering therapy.

Evolocumab treatment in patients with HIV and hypercholesterolemia/mixed dyslipidemia: BEIJERINCK study design and baseline characteristics

People living with human immunodeficiency virus (PLHIV) are at higher risk of atherosclerotic cardiovascular disease (ASCVD) due to traditional and HIV- or antiretroviral treatment (ART)-related risk factors. The use of high-intensity statin therapy is often limited by comorbidities and drug-drug interactions with ART. Herein, we present the design and baseline characteristics of the BEIJERINCK study, which will assess the safety and efficacy of evolocumab in PLHIV and hypercholesterolemia/mixed dyslipidemia. Randomized, double-blind, placebo-controlled, multinational trial that investigates monthly subcutaneous evolocumab 420 mg versus placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia who are treated with maximally-tolerated statin therapy. The primary outcome is the baseline to week 24 percent change in low density lipoprotein cholesterol (LDL-C). Secondary outcomes include achievement of LDL-C < 70 mg/dL and percent change in other plasma lipid and lipoprotein levels. Safety will also be examined. This study enrolled and dosed 464 patients who had a mean age of 56.4 years and were mostly male (82.5%). Mean duration with HIV was 17.4 years, and, by design, HIV viral load at screening was ≤50 copies/mL. ASCVD was documented in 35.6% of patients. Mean LDL-C of enrolled patients at baseline was 133.3 mg/dL. Statin use was prevalent (79.3% overall) with 74.6% receiving moderate or high-intensity statins. In total, 20.7% of patients did not receive statins due to intolerance/contraindications. The BEIJERINCK study is the first clinical trial to examine the lipid-lowering efficacy and safety of a fully human PCSK9 monoclonal antibody inhibitor in a moderate/high cardiovascular risk population of PLHIV.

Trends in high intensity statin use among secondary prevention patients 76 years and older.

Background:High intensity statin therapy (HIST) is the gold standard therapy for decreasing the risk of recurrent atherosclerotic cardiovascular disease (ASCVD); however, little is known about the use of HIST in older adults with ASCVD.Objectives:The aim of this cross-sequential study was to determine trends in statin intensity in older adults over a 10-year timeframe.Methods:The study was conducted in an integrated healthcare delivery system. Patients were 76 years or older with validated coronary ASCVD. Data were collected from administrative databases. Statin intensity level was assessed in eligible patients on January 1st and July 1st from January 1, 2007 to December 31, 2016.Results:Overall, a total of 5,453 patients were included with 2,119 (38.9%) and 3,334 (61.1%) categorized as HIST and Non-HIST, respectively. Included patients had a mean age of 79.8 years and were primarily male and white and had a cardiac intervention. The rate of HIST use increased from 14.5% to 41.3% over the study period (p<0.001 for trend). Conversely, the rates of moderate and low intensity statin use decreased from 61.8% and 9.8% to 41.2% and 4.8%, respectively (both p<0.001 for trend). Similar trends were identified for females and males.Conclusions:The percentage of patients with ASCVD 76 years and older who received HIST substantially increased from 2007 to 2016. This trend was identified in both females and males. Future comparative effectiveness research should be conducted in this patient population to examine cardiac-related outcomes with HIST and Non-HIST use.

The Role of PCSK9 Inhibitors in the Improvement of Outcomes in Patients after Acute Coronary Syndrome: Results of ODYSSEY OUTCOMES Trial

The aim of this review was to present the recently published results of ODYSSEY OUTCOMES trial and discuss the clinical perspective of these data. Patients with acute coronary syndrome are at very high risk of recurrent ischemic cardiovascular complications, especially during the first year after the event. The use of high-intensity statin therapy in this group of patients does not always lead to the achievement of target levels of atherogenic lipoproteins. PCSK9 inhibitors, administered in addition to statins, can provide additional reduction of low-density lipoprotein cholesterol, which leads to further improvements of outcomes in patients with atherosclerotic cardiovascular disease. According to the latest results from ODYSSEY OUTCOMES trial, among patients with recent acute coronary syndrome, who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who were treated with alirocumab then among those who received placebo. The treatment with alirocumab in patients with recent acute coronary syndrome was associated with reduction in death from any causes. The absolute risk reduction with alirocumab was the most prominent in the subpopulation of patients with low-density lipoprotein cholesterol ≥2,6 mmol/l at baseline. These results have implication for clinical practice and may play an important role for the improvement of outcomes in patients at highest cardiovascular risk after acute cardiovascular syndrome.

Long-term benefits of high-intensity atorvastatin therapy in Chinese acute coronary syndrome patients undergoing percutaneous coronary intervention: A retrospective study.

There is lack of long-term data on high-intensity statin therapy of Chinese acute coronary syndrome (ACS) patients scheduled to undergo percutaneous coronary intervention (PCI). In this retrospective study, we compared the long-term efficacy and safety of high-intensity and conventional atorvastatin therapy in reducing low-density lipoprotein cholesterol (LDL-C) and plaque size, and improving cardiac function of ACS patients who underwent PCI.We retrospectively analyzed the clinical records of 120 consecutive ACS patients who underwent PCI at our hospital. Group I received a loading dose of atorvastatin (80 mg/day) prior to PCI, followed by a maintenance dose of 40 mg/day for 3 months post-PCI. Group II received a regular dose of atorvastatin (20 mg/day) from the date of admission until 1 year post-PCI. The composite primary efficacy end point was the mean percent change in calculated LDL-C from baseline to week 48 in both groups and percentage of patients achieving the LDL-C target of ≤1.81 mmol/L.Group I had significantly higher mean baseline LDL-C than group II. Moreover, 8.3% of group I patients had an LDL-C ≤1.81 mmol/L versus 43.3% for group II. At week 24, 75.0% and 90.0% of group I and II patients, respectively, achieved the LDL-C target. At week 48, 85.0% and 96.7% of group I and II patients, respectively, achieved the LDL-C target. Additionally, the mean percent changes at week 4 from baseline in LDL-C were −33.6% ± 20.0% for group I versus −12.8% ± 19.6% for group II, and −47.0% ± 25.5% at week 48 for group I versus −36.4% ± 20.2% for group II. Meanwhile, significant reduction in plaque size and marked improvement in cardiac function were seen in patients receiving high-intensity atorvastatin therapy.Compared to conventional therapy, high-intensity statin therapy is more effective in reducing LDL-C and improving cardiac function of ACS patients, with a general benign safety profile over a period of 48 weeks. Our findings support the use of high-intensity statin therapy for Chinese ACS patients to improve the proportion of patients attaining the LDL-C target and reduction in plaque size and improvement cardiac function.

Trends in high-intensity statin use and low-density lipoprotein cholesterol control among patients enrolled in a clinical pharmacy cardiac risk service

Although high-intensity statin therapy (HIST) is recommended for most patients between 21 and 75years of age with atherosclerotic cardiovascular disease (ASCVD), several recent analyses examining contemporary statin use trends have identified a clinical care gap in the utilization of HIST. The objective of this study was to assess secular trends in lipid management for patients with ASCVD enrolled in a clinical pharmacy program within an integrated health care delivery system. We performed serial cross-sectional studies over time, comprising 18,006 adults with both acute and chronic ASCVD, to assess trends in statin use and low-density lipoprotein cholesterol (LDL-C) levels from 2007 to2016. Although the use of statin therapy (any intensity) remained relatively consistent throughout the 10-year study period (89% in 2007, 87% in 2016), the proportion of patients receiving HIST increased over time (44% in 2007, 67% in 2016; P<.001 for trend). Population mean LDL-C levels ranged from 73 to 83mg/dL with a downward trend over the 10-year study period (P<.001 for trend). By 2016, the proportion of patients attaining an LDL-C <100mg/dL and <70mg/dL was 85% and 54%, respectively. Nonstatin lipid-lowering therapy use decreased over the study period, which was primarily driven by decreased use of ezetimibe (24% in 2007, 2% in 2016; P<.001 for trend). Among adults with ASCVD enrolled in a clinical pharmacy cardiac risk reduction service, guideline-directed use of HIST significantly increased over the past 10years and coincided with decreased population LDL-C levels.

Use of High-Intensity Statin Strategy. Are the Guidelines Followed?

Background: Secondary prevention in patients < 76 years with history of a vascular event or previous revascularization includes the use of high intensity-statin therapy. Objective: The aim of this study is to evaluate the 1-year adherence to treatment since patients’ discharge from the coronary care unit. Methods: We conducted a prospective study of consecutive patients between January and November 2015. Median follow-up was 9 months. Results: A total of 210 patients were included; 83% were men and median age was 59 years (52-67.5). Most patients (74.5%) were discharged with atorvastatin 40 mg/day, 19% with rosuvastatin 20 mg/day, 2.7% with atorvastatin 80 mg/day and 3.9% with rosuvastatin 40 mg/day. Half of the patients continued with high-intensity statins, 28% reduced the dose and 22% stopped the treatment. Conclusions: Only half of the patients with high vascular risk or history of recent revascularization continues with the treatment after one year.

Best Treatment Strategies With Statins to Maximize the Cardiometabolic Benefits

Statins are important for preventing adverse cardiovascular events in patients with both high and low risk of vascular disease, by reducing the levels of low-density lipoprotein cholesterol (LDL-C). However, statins dose-dependently increase adverse effects and increase the risk of type 2 diabetes. Previously, it was hypothesized this was caused by to off-target effects, but recent studies demonstrate it is caused by on-target effects. Nonetheless, the American guidelines recommend the use of high-intensity statin therapy, and extend its use to most people at risk of vascular diseases, particularly older people. In contrast, European, Korean, and Japanese committees have expressed concerns about the potential adverse effects of using high-intensity statins for lifelong periods in a large fraction of the population. Patients who have achieved LDL-C levels below currently recommended targets may still experience cardiovascular events, resulting from residual risk. Ezetimibe, PCSK9 inhibitors, inclisiran, and ANGPTL3 antisense oligonucleotides are promising alternative non-statin drugs. Of interest, cross-talk between hypercholesterolemia and the renin-angiotensin-system exists at multiple levels of insulin resistance and endothelial dysfunction. There are still unanswered questions on how to maximize the cardiometabolic benefits of statins in patients. We will discuss the results of randomized clinical trials, meta-analysis, and recent clinicopharmacogenetic studies, and propose practical guidelines to maximize the cardiometabolic benefits while reducing adverse effects and overcoming residual risk.

Statins at Discharge in Acute Coronary Syndromes over the past 10 Years. The Epi-Cardio Registry

Background: Statins have been incorporated for secondary prevention of cardiovascular disease for over two decades, with a remarkable impact in reducing morbidity and mortality. Currently, the evidence available recommends the use of high-intensity statin therapy in all the patients presenting an acute coronary syndrome. Objective: The aim of this study was to evaluate the use of statins at discharge in acute coronary syndrome patients included in the Epi-Cardio registry and its variation over the past 10 years. Methods: Patients hospitalized between 2005 and 2014 with diagnosis of acute coronary syndrome were included; those deceased or without data of the treatment at discharge were excluded. The frequency of indication of statins, agents, doses used over the 10-year period and the indication of high-intensity therapy (rosuvastatin 20-40 mg, atorvastatin 40-80 mg) were analyzed. The use according to the field of care was compared. Results: 22,905 records were analyzed. The most common agents used were atorvastatin 68%, simvastatin 22.7% and rosuvastatin 9.1%. The temporal trend revealed higher frequency of statin prescription (from 83% in 2005-2007 to 92.5% in 2014), higher doses, lower indication of simvastatin and higher of other agents, and greater use of high-intensity statin therapy from 7.7% in 2005-2007 to 52.6% in 2014. The use of high-intensity therapy was lower in the public health care system.Conclusions: The frequency of statin indication reaches optimal levels and the use of high-intensity therapy increased during the period evaluated, including over half of the patients. The differences in the public health care system suggest a lower access to treatment. Additional studies are necessary to identify the barriers for implementing high-intensity statin therapy.

Abstract 12169: LDL-C Levels and Treatment Patterns Among Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry

Introduction: In the US, LDL-C levels and treatment patterns of patients with familial hypercholesterolemia (FH) – a group prioritized for statin therapy in the 2013 ACC/AHA cholesterol guidelines – remain poorly described. In 2013 the FH Foundation launched the CAscade SCreening for Awareness and DEtection (CASCADE) of FH Registry, the only active US FH patient registry addressing this knowledge gap. Methods: We conducted a 2-year (2013-2015) cross-sectional analysis among 1,295 adults with heterozygous FH enrolled in the CASCADE FH Registry from 10 US lipid clinics. Results: Mean (SD) age at enrollment was 54 (16) years; mean age at FH diagnosis was 45 (19) years; 59% were female; and 80% were white. Mean pretreatment and post-treatment LDL-C levels were 256 (66) and 156 (71) mg/dl, respectively. At enrollment, 43% of patients were taking high-intensity statin therapy; 25% were not taking a statin; and 45% received &gt;1 LDL-lowering therapy. Among FH patients on LDL-lowering therapy, 25% achieved an LDL-C &lt;100 mg/dl, and 41% achieved a ≥50% LDL-C reduction (Table). Factors associated with a ≥50% LDL-C reduction included high-intensity statin use (adjusted OR 2.24, 95% CI 1.47-3.42) and use of &gt;1 LDL-lowering therapy (1.94, 1.29-2.93) (Figure). Atherosclerotic cardiovascular disease (ASCVD) was present in 37%, of whom 44% achieved a ≥50% LDL-C reduction and 9% achieved an LDL-C &lt;70 mg/dl. Conclusions: Despite the high prevalence of ASCVD, several care gaps exist for FH patients enrolled in the CASCADE US registry: lack of early diagnosis, insufficient use of high-intensity statin therapy, and failure to achieve adequate LDL-C reductions.

Impact of Baseline Lipoprotein and C-Reactive Protein Levels on Coronary Atheroma Regression Following High-Intensity Statin Therapy

Guidelines now recommend high-intensity statin therapy in all patients with proven atherosclerotic disease. Yet the impact of baseline lipoprotein and C-reactive protein (CRP) levels on measures of disease regression to this therapy are unknown. The aim of this study was to test the hypothesis that high-intensity statin therapy causes equivalent degrees of coronary atheroma regression irrespective of baseline lipoprotein and CRP levels. In 8 prospective randomized trials using serial coronary intravascular ultrasound, 1,881 patients who maintained or switched to 18- to 24 months of high-intensity statin therapy (rosuvastatin 40 mg or atorvastatin 80 mg) were stratified according to baseline lipoprotein and CRP levels. Changes in coronary percentage atheroma volume (PAV) and total atheroma volume (TAV) were evaluated. High-intensity statin therapy produced significant reductions from baseline in low-density lipoprotein cholesterol by 38.4%, non-high-density lipoprotein (HDL) cholesterol by 33.6%, triglycerides by 13.1%, and CRP by 33.3%, while increasing HDL cholesterol by 11.7% (p <0.001 for all). This was associated with regression of PAV by 0.7% and of TAV by 8.2 mm(3) (p <0.001 for both). No significant differences of changes in PAV and TAV were observed across baseline quintiles of low-density lipoprotein cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, or CRP. Moreover, across all measured lipoproteins and CRP, most patients demonstrated plaque regression (defined as any change from baseline in PAV or TAV <0). In conclusion, high-intensity statin therapy attenuated the natural progression of coronary atherosclerosis in all strata of patients with coronary artery disease irrespective of baseline lipoprotein or CRP levels. These findings provide support for the latest United States guideline recommendations for the broad use of high-intensity statin therapy in all patients with atherosclerosis, regardless of baseline lipid status.

Use of high-intensity statin therapy with simvastatin 80 mg and atorvastatin 80 mg in primary care

Cardiovascular disease (CVD) is the most common cause of death worldwide. Pharmaceutical risk reduction with high-intensity statin therapy is advisable for high-risk patients. Clinicians face a conflict between prescribing for cost (simvastatin 80 mg) or for efficacy (atorvastatin 80 mg). The aim of this audit was to examine the use, efficacy and tolerability of high intensity statin treatment (simvastatin 80 mg; atorvastatin 80 mg) in primary care. Electronic medical records were examined from two general practitioners' surgeries. Analyses involved Mann-Whitney U and χ(2) tests. A total of 116 patients had taken simvastatin 80 mg or atorvastatin 80 mg. Patients were similar between treatment groups: mostly men (62.9%), over 60 years old (68.1%), non-smokers (81.0%) taking statins for secondary prevention (56.9%). More patients on simvastatin withdrew from treatment as a result of inefficacy (49.3% vs. 23.2%, p=0.025) compared with the atorvastatin group. Furthermore, patients on simvastatin were more likely to be failing conventional targets of lipid control, compared with patients on atorvastatin 80 mg (43.5% vs. 21.3%, p=0.006). Tolerability was similar between the two groups. UK guidelines recommend simvastatin 80 mg as an economic choice, despite scant evidence at this dose and recent safety concerns. Conversely, robust evidence exists for atorvastatin 80 mg. Head-to-head clinical trials or clinical studies comparing these agents are lacking. The present study suggests that atorvastatin 80 mg compares favourably to simvastatin in terms of efficacy and has a similar tolerability profile. This retrospective observational study suggests that despite national guidelines, atorvastatin 80 mg is used in clinical practice and is more effective and at least as well tolerated as simvastatin 80 mg.