Abstract 13787: Efficacy of Lowering Low-density Lipoprotein Cholesterol in Elderly Subjects: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Baris Gencer ◽  
Nicholas A Marston ◽  
KyungAh Im ◽  
Peter S Sever ◽  
Anthony C Keech ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Coronary Revascularization ◽  
The Elderly ◽  
Lipid Lowering ◽  
Elderly Subjects ◽  
Lipid Lowering Therapy ◽  
Vascular Events ◽  
Randomized Controlled ◽  
Lowering Therapy ◽  
Myocardial Infraction

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.

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

Circulation ◽  
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.

scholarly journals Stroke Prevention: Little-Known and Neglected Aspects

2021 ◽  
pp. 1-14
Author(s):  
M. Reza Azarpazhooh ◽  
Chrysi Bogiatzi ◽  
J. David Spence
Keyword(s):  
Stroke Prevention ◽  
Oral Anticoagulants ◽  
Blood Pressure Reduction ◽  
The Elderly ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Enteric Coating ◽  
Asymptomatic Carotid ◽  
Lowering Therapy ◽  
Direct Acting

Combining available therapies has the potential to reduce the risk of stroke by 80% or more. A comprehensive review of all aspects of stroke prevention would be very lengthy; in this narrative review, we focus on some aspects of stroke prevention that are little-known and/or neglected. These include the following: (1) implementation of a Mediterranean diet; (2) B vitamins to lower homocysteine; (3) coordinated approaches to smoking cessation; (4) intensive lipid-lowering therapy; (5) lipid lowering in the elderly; (6) physiologically individualized therapy for hypertension based on renin/aldosterone phenotyping; (7) avoiding excessive blood pressure reduction in patients with stiff arteries; (8) treatment of insulin resistance with pioglitazone in stroke patients with prediabetes and diabetes; (9) impaired activation of clopidogrel in patients with variants of CYP2C19; (10) aspirin pseudoresistance due to enteric coating; (11) rationale for anticoagulation in patients with embolic stroke of unknown source; (12) pharmacologic properties of direct-acting oral anticoagulants that should be considered when choosing among them; (13) the identification of which patients with asymptomatic carotid stenosis are at a high enough risk to benefit from carotid endarterectomy or stenting; and (14) the importance of age in choosing between endarterectomy and stenting. Stroke prevention could be improved by better recognition of these issues and by implementation of the principles derived from them.

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

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.

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

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.

scholarly journals Time‐Dependent Cardiovascular Treatment Benefit Model for Lipid‐Lowering Therapies

2020 ◽  
Vol 9 (15) ◽  
Author(s):  
Irfan Khan ◽  
Eric D. Peterson ◽  
Christopher P. Cannon ◽  
Lauren E. Sedita ◽  
Jay M. Edelberg ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Time Dependent ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Treatment Benefit ◽  
Randomized Controlled ◽  
Lowering Therapy ◽  
Dependent Model ◽  
Time Dependent Model

Background With the availability of new lipid‐lowering therapy options, there is a need to compare the expected clinical benefit of different treatment strategies in different patient populations and over various time frames. We aimed to develop a time‐dependent model from published randomized controlled trials summarizing the relationship between low‐density lipoprotein cholesterol lowering and cardiovascular risk reduction and to apply the model to investigate the effect of treatment scenarios over time. Methods and Results A cardiovascular treatment benefit model was specified with parameters as time since treatment initiation, magnitude of low‐density lipoprotein cholesterol reduction, and additional patient characteristics. The model was estimated from randomized controlled trial data from 22 trials for statins and nonstatins. In 15 trials, the new time‐dependent model had better predictions than cholesterol treatment trialists’ estimations for a composite of coronary heart disease death, nonfatal myocardial infarction, and ischemic stroke. In explored scenarios, absolute risk reduction ≥2% with intensive treatment with high‐intensity statin, ezetimibe, and high‐dose proprotein convertase subtilisin/kexin type 9 inhibitor compared with high‐ or moderate‐intensity statin alone were achieved in higher‐risk populations with 2 to 5 years of treatment, and lower‐risk populations with 9 to 11 years of treatment. Conclusions The time‐dependent model accurately predicted treatment benefit seen from randomized controlled trials with a given lipid‐lowering therapy by incorporating patient profile, timing, duration, and treatment type. The model can facilitate decision making and scenario analyses with a given lipid‐lowering therapy strategy in various patient populations and time frames by providing an improved assessment of treatment benefit over time.

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