Impact of lipid‐lowering therapy on the prevalence of dyslipidaemia in patients at high‐risk of cardiovascular events in
            UK
            primary care – a retrospective database study

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C>10.3 mmol/l, LDL-C>8.0 mmol/l+ 1 high-risk feature, LDL-C>4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction>50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 <0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] <0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction>50% 21.3% 49.8% <0.0001 High-intensity statin (%) 13.3% 42.3% <0.0001 PCSK9 inhibitor (%) 6.3% 21.2% <0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.

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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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Becoming more focused therapeutic lipid patterns: results from the Hungarian MULTI GAP 2010

Orvosi Hetilap ◽

10.1556/oh.2011.29127 ◽

2011 ◽

Vol 152 (21) ◽

pp. 822-827 ◽

Cited By ~ 2

Author(s):

István Reiber ◽

György Paragh ◽

László Márk ◽

Gyula Pados

Keyword(s):

High Risk ◽

Goal Attainment ◽

Treatment Strategies ◽

Hdl Cholesterol ◽

High Risk Group ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

Frequent Use ◽

Risk Patients

Previous studies have found that many high-risk patients are not achieving their LDL-cholesterol goals, and many patients, despite being treated with lipid-lowering therapy, also have elevated triglycerides and/or low levels of HDL-cholesterol. Aims: Authors analyzed the treatment strategies for dyslipidemic subjects following cardiovascular events similarly to their former survey from 2008 and 2009. Methods: In the MULTI GAP (MULTI Goal Attainment Problem) 2010 trial data from standard and structured questionnaires of 2332 patients were processed. Authors analyzed the proportion of the patients reaching target levels for total cholesterol, LDL-C, HDL-C, A-C (atherogen cholesterol) and triglyceride. Results: 15% (n = 355) of the patients did not receive any lipid lowering treatment. 44% of the patients treated by specialists reached the target LDL-C level of 2.5 mmol/l. In „high risk” group target levels for HDL-C were reached by 61% of the patients, and for triglyceride by 43% of the subjects. 43% of the patients with the best compliance (>90%) reached the target LDL-C level of 2.5 mmol/l. Conclusion: There is a need for more effective lipid lowering therapy with more frequent use of higher doses of statins or combinations of lipid lowering drugs. Orv. Hetil., 2011, 152, 822–827.

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Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?

European Journal of Preventive Cardiology ◽

10.1177/1741826711406616 ◽

2011 ◽

Vol 19 (3) ◽

pp. 474-483 ◽

Cited By ~ 9

Author(s):

R Ara ◽

A Pandor ◽

J Stevens ◽

R Rafia ◽

SE Ward ◽

...

Keyword(s):

Primary Care ◽

Cardiovascular Events ◽

Cost Effective ◽

Effective Alternative ◽

Lipid Lowering ◽

High Dose ◽

Lipid Lowering Therapy ◽

Coronary Syndrome ◽

Cost Effective Alternative ◽

The Cost

Background: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. Methods and results: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose–response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. Conclusion: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.

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Effective Lipid-lowering Therapy in High-risk Patients

European Journal of Cardiovascular Medicine ◽

10.5083/ejcm.20424884.211 ◽

2011 ◽

Vol 1 (111) ◽

Author(s):

John J.P. Kastelein ◽

Benoit J Arsenault ◽

Jean-Claude Tardif

Keyword(s):

High Risk ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

High Risk Patients ◽

Lowering Therapy ◽

Risk Patients

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Lipid-Lowering Therapy in High-Risk Persons

Comprehensive Therapy ◽

10.1385/comp:32:2:68 ◽

2006 ◽

Vol 32 (2) ◽

pp. 68-73 ◽

Cited By ~ 1

Author(s):

Wilbert S. Aronow

Keyword(s):

High Risk ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy

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SAT-566 Avoiding the Heartache: A Case of Familial Hypercholesterolemia

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.893 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Mustafa Kinaan ◽

Arelys Ramos Rivera ◽

Hanford Yau

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

Risk Stratification ◽

Total Cholesterol ◽

Cardiovascular Events ◽

Total Cholesterol Level ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

History Of

Abstract More than 70% of individuals with atherosclerotic cardiovascular disease are believed to have underlying gene-linked mechanisms leading to hyperlipidemia. It is estimated that 1 in 200 individuals in the United States has heterozygous Familial Hypercholesterolemia (FH). We present a case that highlights the importance of comprehensive care for a patient with heterozygous FH, from screening and risk stratification, to therapy. Our patient is a 43-year-old gentleman with history of hyperlipidemia. At age 25, he was diagnosed with hyperlipidemia and was started on statin therapy. He has strong family history of cardiovascular disease. His mother had her first myocardial infarction (MI) at age 40 and required coronary artery bypass. She also suffered from three strokes. His maternal aunt and uncle suffered from MIs at age 38 and 40, respectively. Additionally, his maternal grandfather passed away from MI at age 38. The patient’s daughter was found to have total cholesterol level > 300 mg/dL at age 8. He does not have history of obesity, diabetes, previous cardiovascular events, or hypothyroidism. He is athletic and follows a healthy diet. He did not have any xanthomas, xanthelasmas, nor arcus cornealis. At time of initial evaluation, the patient had low-density lipid (LDL) level of 180 mg/dL despite therapy with rosuvastatin, ezetimibe, and niacin. Based on these findings, we proceeded with genetic testing. Results of testing showed a heterozygous c.6delG (p.Trp4Glyfs*202) pathogenic mutation of the LDL receptor. We also obtained cardiovascular risk stratification studies. On cardiac CT angiogram, he was found to have extensive, four-vessel disease with 80-90% stenosis of the left ascending artery (LAD) with coronary calcium score of 136 and total score of 219 (99th percentile). Exercise, stress myocardial perfusion scan showed small reversible anteroseptal perfusion abnormality suggestive of mild to moderate ischemia. LAD stenosis was confirmed on a left heart catheter, but no intervention was required. We proceeded with aggressive lipid-lowering therapy with rosuvastatin 40mg daily and alirocumab 300mg monthly. He was also started on aspirin and beta-blocker given coronary artery disease. Following initiation of therapy, the patient’s LDL level dropped to 51 mg/dL with total cholesterol level of 153 mg/dL, HDL of 47mg/dL, and triglycerides of 109 mg/dL. The patient was encouraged to seek genetic counseling for his children and first degree relatives. His daughter was started on rosuvastatin 7.5mg daily by her pediatrician. The patient has not suffered any cardiovascular events and continues to follow up for therapy. Without aggressive lipid-lowering therapy, the lifespan of FH patients can be significantly shortened. Therefore, identifying FH patients is imperative to prevent cardiovascular disease in these patients and their afflicted family members.

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The Effect of Switching to the High-Efficient Rosuvastatin on the Success of Lipid Lowering Therapy in High Risk Patients. The CORVUS (Controlled Targets for High Vascular Risk Patients Using Effective Statins) Study

Pharmaceutica Analytica Acta ◽

10.4172/2153-2435.1000267 ◽

2013 ◽

Vol 04 (08) ◽

Author(s):

Istvan Reiber

Keyword(s):

High Risk ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Vascular Risk ◽

High Risk Patients ◽

Lowering Therapy ◽

High Efficient ◽

Risk Patients

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