Statin therapy/lipid lowering therapy among Indian adults with first acute coronary event: The dyslipidemia Residual and Mixed Abnormalities IN spite of Statin therapy (REMAINS) study

Introduction: The clinical benefit from LDL-C lowering therapy in the elderly remains debated. Aim: To synthesize the efficacy of lowering LDL-C in patients aged ≥75 years in the light of most recently published data. Methods: Medline database was searched for the most recent evidence (2015-2020). The key inclusion criterion was a randomized controlled cardiovascular outcome trial testing an LDL-C lowering therapy with data available in patients aged ≥75 years at randomization. For efficacy, we meta-analyzed the risk ratio (RR) of major vascular events (a composite of cardiovascular (CV) death, myocardial infarction, stroke or coronary revascularization) per 1-mmol/L reduction in LDL-C. Results: Among 244,090 patients from 29 trials, 21,492 (8.8%) were elderly; 11,750 from statin trials, 6209 from ezetimibe trials, and 3533 from PCSK9 inhibitor trials. Median follow-up ranged from 2.2-6.0 years. LDL-C lowering therapy significantly reduced major vascular events (n=3519) in the elderly by 26% per 1-mmol/L LDL-C reduction (RR 0.74 [0.61-0.89], P=0.002), which was at least as good as the magnitude of effect seen in the non-elderly patients (RR 0.85 [0.78-0.92]; P interaction =0.24). Amongst the elderly, the RR was similar for statin (0.81 [0.70-0.94]) and non-statin therapy (0.67 [0.47-0.95]; P interaction =0.60). The benefit of LDL-C lowering in the elderly was observed for each component of the composite, including CV death (RR 0.85 [0.73-0.996], P=0.045), myocardial infraction (RR 0.80 [0.70-0.92], P=0.001), stroke (RR 0.71 [0.58-0.87], P=0.001) and coronary revascularization (RR 0.78 [0.63-0.96], P=0.017). Conclusion: In patients 75 years and older, lipid-lowering therapy is as effective in reducing CV events as it is in younger adults. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin therapy, in the elderly.

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P5015Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events: A meta-analysis

European Heart Journal ◽

10.1093/eurheartj/ehz746.0193 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

I Dykun ◽

R Mincu ◽

M Totzeck ◽

T Rassaf ◽

A A Mahabadi

Keyword(s):

Myocardial Infarction ◽

Relative Risk ◽

Statin Therapy ◽

Risk Reduction ◽

Cardiovascular Events ◽

Ldl Cholesterol ◽

Meta Analysis ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy

Abstract Background Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors allow for reduction in LDL-cholesterol in addition to statin therapy. Purpose To perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe or PCSK-9 inhibitor in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of November 2018, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were “ezetimibe”, “evolocumab”, “alirocumab”, or “bococizumab” and “cardiovascular events”. Results A total of 100,610 patients from 9 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, SIPRE I, SPIRE II, ODYSSEY LONG TERM, OSLER-1 and OSLER-2, HIJ-PROPER) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 18% risk reduction in cardiovascular events (OR [95% CI]: 0.82 [0.75–0.89]). Effect sizes were similar for myocardial infarction (0.84 [0.76–0.92]) and even more pronounced for ischemic stroke (0.77 [0.67–0.83]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.94 [0.85–1.05]). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Comparing efficacy of LDL-reduction and relative risk redaction of cardiovascular events, a linear relationship was observed (figure). Figure 1. Correlation of reduction of LDL-cholesterol at one year with relative risk reduction (95% confidence interval) of cardiovascular events in included trials. Conclusion Intensified LDL-lowering therapy with ezetimibe or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. There is a linear relationship between LDL reduction and cardiovascular risk reduction, confirming the beneficial effects of LDL lowering therapy beyond statins in secondary prevention.

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PCSK9 inhibitors for in-hospital treatment of patients with acute coronary syndrome and severe lipid metabolism disorders

Russian Journal of Cardiology ◽

10.15829/1560-4071-2020-4010 ◽

2020 ◽

Vol 25 (8) ◽

pp. 4010

Author(s):

O. L. Barbarash ◽

N. V. Fedorova ◽

D. Yu. Sedykh ◽

O. V. Gruzdeva ◽

O. N. Khryachkova ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Statin Therapy ◽

Lipid Lowering ◽

High Density Lipoproteins ◽

Hospital Treatment ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitor ◽

Coronary Syndrome ◽

Lowering Therapy ◽

Baseline Values

Aim. To assess the efficacy and safety of PCSK9 inhibitor alirocumab as part of a combination lipid-lowering therapy in patients with acute coronary syndrome (ACS).Material and methods. This prospective, open-label, single-center activetreatment study included 13 patients hospitalized due to ACS. The main inclusion criterion was nonachievement of target low-density lipoprotein cholesterol (LDL-C) values (<1,4 mmol/L) with high-intensity statin therapy prior to ACS. During the first 30 days after ACS, all patients received therapy with atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day in combination with alirocumab 150 mg/ml (Praluent) administered by subcutaneous injection. Lipid and biochemical profiles were monitored. The first injection of the PCSK9 inhibitor was performed on days 3-5 of hospitalization, the second — after 2 weeks.Results. On admission, the median LDL-C was 4,3 [3,5;5,3] mmol/L. A day after administration, there was a decrease in LDL-C by 41,9% (median 2,5 [1,8;3,2] mmol/L; p=0,001) without a negative effect on high-density lipoproteins (HDL-C) (median 1,2 [0,8;1,4] mmol/L; p=0,270). Before the next injection, LDL-C decreased by another 8% (median 2,3 [1,1;4,1] mmol/L). A day after the second injection, a decrease in LDL-C from the baseline values was 69,8% (median 1,3 [0,7;1,5] mmol/L; p=0,010). Strengthening lipid-lowering therapy with a PCSK9 inhibitor within 30 days after ACS did not lead to clinical and biochemical deterioration.Conclusion. The use of subcutaneous 150-mg injections of alirocumab 2 times a week 30 days after ACS in patients who did not reach target LDL-C values with statin therapy, leads to a 69% decrease in LDL-C from baseline values and is safe.

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DOES AGGRESSIVE STATIN THERAPY REDUCE CORONARY ATHEROSCLEROTIC PLAQUE LIPID CONTENT? RESULTS FROM: REDUCTION IN YELLOW PLAQUE BY AGGRESSIVE LIPID LOWERING THERAPY (YELLOW) TRIAL

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(12)60305-2 ◽

2012 ◽

Vol 59 (13) ◽

pp. E304 ◽

Cited By ~ 7

Author(s):

Annapoorna Subhash Kini ◽

Pedro Moreno ◽

Jason Kovacic ◽

Atul Limaye ◽

Ziad Ali ◽

...

Keyword(s):

Statin Therapy ◽

Atherosclerotic Plaque ◽

Lipid Content ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

Yellow Plaque ◽

Coronary Atherosclerotic Plaque

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Lipid Lowering Therapy with Statins in Patients with Heterozygous Familial Hypercholesterolemia

Kardiologiia ◽

10.18087/cardio.2019.3.10238 ◽

2019 ◽

Vol 59 (3) ◽

pp. 27-35

Author(s):

V. A. Korneva ◽

T. Yu. Kuznetsova ◽

G. P. Tihova

Keyword(s):

Statin Therapy ◽

Familial Hypercholesterolemia ◽

Low Density Lipoprotein ◽

Myocardial Revascularization ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Factors Associated ◽

Lowering Therapy ◽

History Of

Aim: to analyze adherence of FH patients with familial hypercholesterolemia (FH) to the statin therapy and reveal factors, which influence it; to assess the degree of target level of low-density lipoprotein cholesterol (LDLCH) achievement by FH patients on statin therapy. Materials and methods. We included in this study 203 FH patients aged >18 years (mean age 50.0±1.1 years, 82 men). Definite FH was diagnosed in 96 persons, in the other patients FH was considered possible. For evaluating the adherence to therapy with statins we used the Morisky-Green questionnaire. Results. Among patients with definite FH 57 % were adherent to lipid-lowering therapy, 16 % were partially adherent, and 27 % – not adherent. Target LDLCH levels were achieved in 22.6 % and 12.5 % of patients with definite and possible FH, respectively. Smoking and gender were not associated with adherence to statin therapy. Factors associated with higher adherence were age (p=0.000003), arterial hypertension (odds ratio [OR] 1.90, 95 % confidence interval [CI] 1.02 to 3.55], p=0.044), ischemic heart disease (IHD) (OR=2.99, 95 %CI 1.50 to 5.97, p=0.002), history of myocardial infarction (MI) (OR 5.26, 95 %CI 2.03 to 13.60, p=0.0006), history of myocardial revascularization (OR 20.3, 95 %CI 2.64 to 156.11, p=0.004) and the fact of achieving target LDLCH level (OR 19.93, 95 %CI 7.03 to 56.50, p<0.0001). The main reason for the refuse from statin therapy in 87 % of patients was fear of side effects. Main reasons for stopping of ongoing therapy were: myalgia, an increase in transaminases, skin rashes, and high cost in 12, 35, 12, and 6 % of patients, respectively. The decision to withdraw therapy with statins was made by 29 % of patients by themselves. Conclusion. In this study 57 % of patients with definite FH were adherent to statin therapy. Factors associated with increased adherence were age, hypertension, IHD, history of MI, history of myocardial revascularization, achievement of target LDLCH level. Target LDLCH levels were achieved by 22.6 and 12.5 %% of patients with definite and possible FH, respectively.

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Lipid profile outcome gaps of Arabs and South Asians receiving chronic Statin therapy

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl4.4442 ◽

2020 ◽

Vol 11 (SPL4) ◽

pp. 2194-2200

Author(s):

Zahra Alagheband ◽

Seeba Zachariah ◽

Dixon Thomas ◽

Dave L Dixon

Keyword(s):

Lipid Profile ◽

Statin Therapy ◽

South Asian ◽

South Asians ◽

Lipid Profiles ◽

Lipid Lowering ◽

P Value ◽

Lipid Lowering Therapy ◽

Therapy Outcomes ◽

Lowering Therapy

Ethnicity is a variable in statin response, but the influence of it in Arabs and South Asians is not known. There is a possibility of under-treatment in the long-term management of dyslipidemia in the Arab population, ignoring post-initiation medication nonadherence and lifestyle. There could be potential genetic reasons also for the need for higher lipid-lowering therapy in Arabs. This study is to identify lipid profile outcome gaps of Arabs and South Asians who were receiving chronic statin therapy. A hypothesis generating retrospective cohort study was conducted to compare lipid profiles among patients treated with a statin for more than three months. The study compared two lipid profiles of Arab and South Asian patients on chronic management of dyslipidemia. T-test and Z-test were performed to compare the lipid profiles. The study participants included 42 Arabs and 28 South Asians. Arabs had a higher body mass index (P-value 0.05), and more of them were smokers compared to South Asians (P-value 0.04). Total cholesterol (P-value 0.03, 95%CI 1.08 to -21.29) and LDL cholesterol (P-value 0.03, 95% CI 0.51 to -17.51) reductions in 3 – 6 months were significant in South Asians, but not in Arabs. The lipid profiles in Arabs receiving chronic statin therapy might be poor compared to South Asians. Both populations need improvements in lipid-lowering therapy outcomes. This hypothesis should be studied further to prove inherent differences and poor therapy outcomes among Arab and South Asian population that might result in modifications in current healthcare management policies.

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Abstract 17862: Benefit and Safety of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes in 4416 Women in the IMPROVE-IT Trial

Circulation ◽

10.1161/circ.132.suppl_3.17862 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Eri Toda Kato ◽

Robert P Giugliano ◽

Michael A Blazing ◽

Erin Bohula May ◽

Sema Guneri ◽

...

Keyword(s):

Statin Therapy ◽

Coronary Revascularization ◽

Composite Endpoint ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Efficacy And Safety ◽

Primary And Secondary Prevention ◽

Primary Composite Endpoint ◽

Lowering Therapy ◽

Prevention Guidelines

Background: Statin therapy is established in primary and secondary prevention guidelines both for men and women, although some people have questioned the benefits in women, where data are more limited. Adding the non-statin ezetimibe to statin therapy further reduced future CV events post ACS in IMPROVE-IT, but detailed analyses by sex have not been reported. Methods: In the IMPROVE-IT trial, patients hospitalized with ACS and LDL-C ≤125 mg/dL were randomized to ezetimibe/simvastatin 40mg (E/S) or placebo/simvastatin 40mg (P/S) and were followed up for a median of 6 yrs. The primary composite endpoint was CVD, MI, hospitalization for UA, coronary revascularization >30 days, and stroke. Efficacy and safety outcomes in women vs men were compared, one of 23 pre-specified subgroups. Results: Among 18144 patients from IMPROVE-IT, 4416 (24%) were women. Compared with men, women were more likely to be older, diabetic, and hypertensive, but less likely to have prior revascularization or multiple vessel disease. At 12 months, the median difference in LDL-C in both women and men was 16 mg/dl between E/S and P/S. Women receiving E/S had a 12% RRR of the primary endpoint (HR vs P/S, 0.88; 95% CI, 0.79 to 0.99), compared with a 5% reduction for men (HR vs P/S; 0.95, 95% CI, 0.90 to 1.01; p interaction p=0.26). There were no differences between E/S and P/S in this or safety events (E/S vs. P/S; AST and/or ALT>3ULN, 2.5% vs. 2.6%, 2.5% vs. 2.2%, cholecystectomy, 1.8% vs. 1.6%, 1.4% vs. 1.4%, myopathy, 0.2% vs. 0.2%, 0.1% vs. 0.1%, gallbladder-related AEs, 3.9% vs. 4.3%, 2.9% vs. 3.3%, in women and in men, respectively, p=all NS). Conclusion: IMPROVE-IT demonstrated that adding ezetimibe to statin reduces LDL-C and CV events in both women and men. A safety profile of ezetimibe supports the use of intensive, combination lipid lowering therapy to optimize CV outcomes in women as well as men.

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Combined lipid-lowering therapy from standpoint of modern guidelines for management of dyslipidaemias

Medical alphabet ◽

10.33667/2078-5631-2021-17-13-19 ◽

2021 ◽

pp. 13-19

Author(s):

O. D. Ostroumova ◽

A. I. Kochetkov ◽

A. I. Listratov

Keyword(s):

Statin Therapy ◽

Safety Profile ◽

High Intensity ◽

Residual Risk ◽

Lipid Lowering ◽

High Density Lipoproteins ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

Increased Risk ◽

Wide Range

Coronary artery disease (CAD) remains the leading cause of death, and its prevalence is projected to increase in the near future. Dyslipidemia is one of the most important risk factors for CAD, and special attention is currently being paid to improving approaches to its correction. In the new revision of the Russian Guidelines for the Management of Patients with dyslipidemia (2020), priorities are given to high-intensity statin therapy: new more strict target levels of low-density lipoprotein cholesterol (LDL–C) are introduced. Experts also emphasize the important role of the cholesterol fraction of non-high-density lipoproteins (non-HDL–C), primarily triglycerides, and introduce their target levels. The concept of residual risk, which remains despite effective statin therapy and achievement of the target level of LDL–C, is closely related to non-HDL–C. Here, hypertriglyceridemia is of crucial importance, contributing to an increased risk of coronary heart disease and cardiovascular mortality. Therefore, combined lipid-lowering therapy in the form of a combination of high-intensity statin and fenofibrate is an effective approach to significantly improve the prognosis and reduce the residual risk. According to research data, rosuvastatin provides a reduction in LDL–C by ≥ 50 %, has a wide range of pleiotropic effects in combination with an optimal safety profile. Fenofibrate allows you to effectively reduce the level of triglycerides and implements additional protective effects on the cardiovascular system. The logical continuation of the principle of combined lipid-lowering therapy was the appearance of a fixed combination (FC) of rosuvastatin and fenofibrate, which already has its own evidence base of studies indicating a complex and complementary effect on the disturbed blood lipid spectrum, a good safety profile of therapy, and the form of ‘single-pill’ significantly increases patients adherence to treatment. It can be expected that the widespread use of rosuvastatin and fenofibrate in clinical practice will effectively reduce the residual cardiovascular risk and thus provide an improved prognosis for patients.

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Effectiveness of lipid-lowering therapy in outpatients with coronary artery disease living in a large industrial center of Eastern Siberia

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2021-3135 ◽

2022 ◽

Vol 20 (8) ◽

pp. 3135

Author(s):

N. G. Gogolashvili ◽

R. A. Yaskevich

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Statin Therapy ◽

High Intensity ◽

Lipid Lowering ◽

Moderate Intensity ◽

Lipid Lowering Therapy ◽

Target Level ◽

Lowering Therapy ◽

Artery Disease

Aim. To study the prescription rate of lipid-lowering therapy and achieving the target low-density lipoprotein cholesterol (LDL-C) values in outpatients with coronary artery disease (CAD) living in Krasnoyarsk.Material and methods. The study included all patients with CAD hospitalized in the cardiology department of the clinic of the Research Institute of Medical Problems of the North (Krasnoyarsk) in 2018-2019. The analysis included data from 1671 patients (men, 770; women, 901). During hospitalization, an in-depth survey of patients was carried out on the subject of prescribing and taking lipid-lowering drugs. On admission, lipid profile was assessed in all patients.Results. At the time of admission, only 51,4% of patients received lipidlowering therapy. The majority received statin monotherapy (99,2%). Only 0,8% of patients received combination therapy (statin+ezetimibe). The most frequently prescribed statin in the study was atorvastatin — 74,6%. Rosuvastatin was received by 17,1% of patients. In most cases, the doses of atorvastatin and rosuvastatin corresponded to the moderate-intensity statin therapy regimen. The frequently prescribed dose of atorvastatin was 20 mg/day — 54,4%, rosuvastatin — 10 mg/day — 68,7%. The target level of LDL-C <1,8 mmol/L was reached by 16,3%, <1,5 mmol/L — by 9,0%, <1,4 mmol/L — only 6,5% of patients. Most often, the target LDL-C levels were achieved by patients receiving high-intensity statin (HIS) therapy. The target level of LDL-C <1,8 mmol/L was reached by 37,5%, <1,5 mmol/L — 23,9%, LDL cholesterol <1,4 mmol/L — 20,7% of patients, receiving HIS.Conclusion. In patients with CAD living in Krasnoyarsk, the most commonly prescribed statins were atorvastatin and rosuvastatin, but only 32% of patients received HIS. Combination lipid-lowering therapy has been used extremely rarely. Among the surveyed patients, the current target level of LDL-C for patients with CAD (<1,4 mmol/L) was achieved only in 6,5% of patients. In the group of patients receiving high-intensity statin therapy, this target level was achieved in 20,7% of patients, which indicates the need for strict adherence to current clinical guidelines.

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Dyslipidemia: Management Using Optimal Lipid-Lowering Therapy

Annals of Pharmacotherapy ◽

10.1345/aph.1r127 ◽

2012 ◽

Vol 46 (10) ◽

pp. 1368-1381 ◽

Cited By ~ 20

Author(s):

Matthew K Ito

Keyword(s):

Cardiovascular Risk ◽

Combination Therapy ◽

Statin Therapy ◽

Risk Reduction ◽

Density Lipoprotein ◽

Lifestyle Changes ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

Intensive Statin Therapy

Objective: To evaluate current approaches and explore emerging research related to dyslipidemia management. Data Sources: MEDLINE (2004-April 2012) was searched for randomized controlled trials using the terms dyslipidemia and lipid-lowering therapy or statin (>1000 hits). Separate searches (MEDLINE, Google) identified meta-analyses (2010–2011), disease prevalence statistics, and current consensus guidelines (2004–July 2011). Additional references were identified from the publications reviewed. Study Selection and Data Extraction: English-language articles on large multi-center trials were evaluated. Data Synthesis: National Cholesterol Education Program Adult Treatment Panel III guidelines for the reduction of cardiovascular risk recommend the attainment of specific low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol (non–HDL-C) target values, based on an individual's 10-year risk of coronary heart disease or global risk. For most patients unable to achieve recommended lipid level goals with therapeutic lifestyle changes, statins are the first option for treatment. Results of large, well-controlled clinical trials have demonstrated that statins are effective in primary and secondary prevention of cardiovascular disease in diverse populations, including patients with diabetes and the elderly, and that intensive statin therapy provides more effective lipid goal attainment and significantly greater risk reduction in patients with coronary artery disease. Stalin therapy is generally well tolerated but may increase the risk of myopathy. Statin use has been associated with increases in hepatic transaminases and an increased risk of diabetes, although the absolute risk of diabetes is low compared with the risk reduction benefit. Combination therapy including a statin may be appropriate for certain populations, but the risk reduction benefits of combination therapy remain unclear. Ezetimibe is an important treatment option for patients with hypercholesterolemia who do not tolerate intensive statin therapy. Although fibrates or niacin improves overall lipid profiles in patients with hypertriglyceridemia or dyslipidemia who are receiving statin therapy, their efficacy in reducing cardiovascular risk remains questionable and their use raises safety and tolerability concerns. Conclusions: Intensifying lifestyle changes and statin dose should be utilized first in patients not achieving their LDL-C and non-HDL-C goals.

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