The problem of safety of lipid-lowering therapy

This study focused on analysis of current publications evaluating safety of lipid-lowering therapy. Search for literature was performed on websites of cardiological societies and online databases, including PubMed, EMBASE, and eLibrary by the following key words: statins, statin intolerance, lipid-lowering therapy, statin safety, and statin аdverse effects. The focus is on statins, in view of the fact that they are the most commonly prescribed, highly effective and safe drugs for primary and secondary cardiovascular prophylaxis. This review consistently summarized information about myopathies, hepatic and renal dysfunction, potentiation of DM, and other possible adverse effects of lipid-lowering therapy. The author concluded that despite the high safety of statins acknowledged by all international cardiological societies, practicing doctors still continue unreasonably cancel statins, exposing the patient under even greater danger. Information about the corresponding author:

Download Full-text

The importance of highly effective lipid-lowering therapy with atorvastatin in the normalization of the autonomic regulation of heart rate in patients with STEMI

European Heart Journal ◽

10.1093/ehjci/ehaa946.0449 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y Barmenkova ◽

E Dushina ◽

N Burko ◽

V Oleinikov

Keyword(s):

Myocardial Infarction ◽

Heart Rate ◽

Troponin I ◽

Cardiac Activity ◽

Autonomic Regulation ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

Target Values ◽

Highly Effective

Abstract Purpose To assess the importance of highly effective lipid-lowering therapy with atorvastatin in the normalization of the autonomic regulation of cardiac activity in patients with myocardial infarction with ST segment elevation (STEMI). Methods The study included 130 patients with STEMI aged 51.3±8.9 years, the majority of males (91%). Inclusion criteria: age from 35 to 70 years, STEMI confirmed by ECG and the level of biomarkers (troponin I, CK-MB), the presence of hemodynamically significant stenosis of a culprit artery according to coronary angiography provided that other coronary arteries are occluded no more than 50%, left main coronary artery - not more than 30%. Exclusion criteria: a history of myocardial infarction, CHF III-IV NYHA, bundle branch block, atrial fibrillation, artificial pacemaker. All patients took atorvastatin at a dose of 40–80 mg/day for 48 weeks after STEMI. As part of a further study at the 7th-9th day and 48 weeks after STEMI, 24-hour ECG monitoring was performed with the Astrocard system. The spectral parameters of heart rate variability (HRV) were evaluated: TotP (ms2), ULF (ms2), VLF (ms2), LF (ms2), HF (ms2), LF / HF. By the 48th week of treatment, patients were divided into groups depending on the achievement of the target level of low density lipoproteins (LDL) of less than 1.4 mmol / l or less than 50% of the initial values: 64 people who reached target values of LDL and formed the group of high-effective lipid-lowering therapy “H”, the group of low effective treatment “L” included 66 patients whose LDL did not meet the recommended level. The groups were matched by gender, age, and anthropometric data. Results In the “H” group, by the 48th week, a pronounced power amplification of all spectral components was obtained. The TotP parameter increased from 13021 (95% CI 10967; 15076) ms2 to 20988 (95% CI 17617; 24358) ms2 (p=0.0001); HF - from 164 (95% CI 105; 222) ms2 to 249 (95% CI 178; 321) ms2 (p=0.003). An increase in the low-frequency components of HRV was observed: an increase in ULF from 10695 (95% CI 8985; 12406) ms2 to 20401 (95% CI 15099; 25703) ms2 (p=0.0001), VLF - from 1473 (95% CI 1212; 1734) ms2 to 1734 (95% CI 1478; 1990) ms2 (p=0.01), LF - from 761 (95% CI 573; 949) ms2 to 909 (95% CI 736; 1082) ms2 (p=0.02). Against the background of an increase in all parameters of the frequency spectrum, the sympathovagal balance coefficient LF / HF decreased from 6.6 (95% CI 5.7; 7.6) to 5.2 (95% CI 4.3; 6.1) ( p=0.004). An analysis of the HRV indicators dynamics in the L group revealed an increase in only the total spectrum power - TotP from 12740 (95% CI 10947; 14533) ms2 to 20195 (95% CI 16619; 23770) ms2. Conclusions Highly effective therapy with atorvastatin in STEMI patients helps to normalize the parameters of the autonomic regulation of heart rate in the post-infarction period due to the increased effects of parasympathetic activity. Funding Acknowledgement Type of funding source: None

Download Full-text

The role of soluble fiber intake in patients under highly effective lipid-lowering therapy

Nutrition Journal ◽

10.1186/1475-2891-10-80 ◽

2011 ◽

Vol 10 (1) ◽

Cited By ~ 21

Author(s):

Silvia C Ramos ◽

Francisco A Fonseca ◽

Soraia H Kasmas ◽

Flávio T Moreira ◽

Tatiana Helfenstein ◽

...

Keyword(s):

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Fiber Intake ◽

Soluble Fiber ◽

Lowering Therapy ◽

Highly Effective

Download Full-text

Exposure to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the association with neurocognitive side effects: a meta-analysis and meta-regression

European Heart Journal ◽

10.1093/ehjci/ehaa946.3339 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B Hirsh-Raccah ◽

A Yanovsky ◽

V Rotshild ◽

H Danenberg ◽

R Eliaz ◽

...

Keyword(s):

Side Effects ◽

Adverse Effects ◽

Meta Analysis ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Proprotein Convertase ◽

Pcsk9 Inhibitors ◽

Lowering Therapy ◽

Meta Regression ◽

Meta Analyses

Abstract Background Lipid lowering therapy may be associated with impaired cognitive function. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse effects remains unclear. Purpose To assess the neurocognitive safety of PCSK9 inhibitors using meta-analysis and meta-regression of randomized controlled trials (RCTs). Methods PubMed (MEDLINE), Embase and Cochrane library were searched. RCTs that reported assessments of neurocognitive outcomes of participants using PCSK9 inhibitors, with a duration of follow up of at least six months were included. The results of the search were screened by two independent reviewers. Any disagreements were resolved by consensus. The research was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for meta-analyses. Results were pooled using random-effects models. The primary safety outcome of this analysis was defined as the reported incidence of neurocognitive adverse effects. Results Results of 21 trials were included in the analysis. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. No significant difference in the incidence of neurocognitive side effects between the treatment and control groups was identified (RR=1.01, 95% CI: 0.86–1.19, I2=3%). Same results were seen in separate analysis for each of the medicines (Alirocumab- RR=0.88, 95% CI: 0.72–1.08, I2=0%, Evolocumab- RR=1.42, 95% CI: 0.74–2.73, I2=55%). In a meta-regression analysis there was no statistically significant association between the assessed and the risk for neurocognitive side effects. Conclusions Pooled results of our meta-analysis and meta-regression clearly show that the exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse events. Due to the increasing proportion of patients using lipid-lowering therapy these results are positively reassuring. However, more data from long-term outcomes studies is needed to further evaluate the effect of longer exposure to PCSK9 inhibitors Funding Acknowledgement Type of funding source: None

Download Full-text

341 Observational multicentre study on effectiveness and tolerability of Alirocumab in real world, the OMERO study: interim data from the first 699 patients

European Heart Journal Supplements ◽

10.1093/eurheartj/suab148.005 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Alberico Luigi Catapano ◽

Aldo Pietro Maggioni ◽

Francesco Rossi ◽

Giampaolo Tirone ◽

Lucia Notarianni ◽

...

Keyword(s):

Real Life ◽

Lipid Lowering ◽

Clinical Judgement ◽

Lipid Lowering Therapy ◽

Dosing Regimen ◽

Statin Intolerance ◽

Lowering Therapy ◽

A Prospective Study ◽

Level Reduction

Abstract Aims OMERO is a prospective study, aimed to assess the long-term effectiveness, tolerability, and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-i), in the real life in Italy. The study is planned to include 800 patients, from 40 Italian sites, treated with alirocumab on top of standard lipid lowering therapy. Methods and results This analysis concerns 699 (out of 800) patients with all data available: 65.5% male; mean age 60.6 ± 11.09 years; 29.6% with HeFH in primary prevention; 70.4% in secondary prevention (with/without HeFH). Before ALI administration, 461 patients (66%) were treated with statins while 231 (33%) reported statin intolerance, that resulted in the statin discontinuation. Mean baseline LDL-C was 161.5 ± (53.07) mg/dl. Based on clinical judgement, ALI was initially prescribed at 75 mg Q2W dosing regimen in 60.80% of participants, whereas the remainder received 150 mg Q2W. At V1 57 patients (89.06%) switch from 75 mg Q2W to 150 mg Q2W and 7 patients (10.94%) from 150 mg Q2W to 75 mg Q2W. LDL-C level reduction from baseline (before ALI administration) to 6 months from the study enrolment (V1), was −45% (V1: mean LDL-C was 73.5 ± 45.70 mg/dl). LDL-C levels at V1 by participant category are shown in Figure 1. The rate of patients with at least one adverse event was 25.6% (of which SAE 7.4%); the rate of patients with at least one related adverse reaction to treatment was 3.8% none of them were serious. Conclusions OMERO confirmed in clinical practice the results observed in trials: a significant reduction of LDL-C was observed with ALI 75/150 mg Q2W in participants at high CV risk with or without HeFH. ALI was generally well tolerated.

Download Full-text

Adverse effects of statin therapy: real evidence

Cardiosomatics ◽

10.26442/22217185.2019.1.190264 ◽

2019 ◽

Vol 10 (1) ◽

pp. 51-61 ◽

Cited By ~ 1

Author(s):

Marina G. Bubnova

Keyword(s):

Side Effects ◽

Adverse Effects ◽

Statin Therapy ◽

Treatment Compliance ◽

Lipid Lowering ◽

Current View ◽

Tolerability Profile ◽

Lipid Lowering Therapy ◽

Statin Intolerance ◽

Good Tolerability

Aim. To provide a current view on the tolerability and safety of statin therapy. Materials and methods. The data of 73 scientific sources from Russian and foreign literature published within 1996-2018 are considered. Results. It is generally accepted that statins are first-line therapeutic agents for hypercholesterolemia and combined hyperlipidemia. Today there in growing evidence that lowering of low-density lipoprotein cholesterol levels prevents atherosclerotic diseases and reduces a risk of cardiovascular and overall mortality. Main issues of current statin therapy include a use of inadequate dosage for atherosclerotic diseases prevention, low treatment compliance and drug intolerance. In recent years the issue of statin intolerance has become of great importance. Criteria were proposed for determining an inability to tolerate statins, some experts suggest replacing definition of “statin intolerance” with the term “statin-associated side-effects”. Most discussed adverse effects due to statins include muscle-related symptoms (myalgia/myopathy), hepatotoxicity (hepatic hyperenzymemia) new-onset diabetes, dementia and cognitive impairment. Mechanisms of development of these adverse effects are still unclear. Certain factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were established. Some factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were identified. Occurrence of statin-associated side-effects depends on statin dose, a patient's age, gender, comorbidity and concomitant therapy. Many adverse effects of statins are drug class effect. At the same time each of statins has specific features of its structure, metabolism, drug interactions and pharmacokinetics. Pitavastatin belongs to the last generation of statins and it has distinct pharmacological features and neutral diabetogenic effects, etc. Risk of adverse effects due to statins is often exaggerated while benefit from the use of statins for preventing atherosclerotic diseases outweighs potential risks. Real occurrence of some adverse effects due to statin therapy requires additional evidence. Conclusion. Overall, statins have a good tolerability profile and are approved for use in the vast majority of patients who required lipid-lowering therapy.

Download Full-text

Autonomic regulation of heart rate against the background of highly effective lipid-lowering therapy in persons with postinfarction remodeling

Atherosclerosis ◽

10.1016/j.atherosclerosis.2021.06.782 ◽

2021 ◽

Vol 331 ◽

pp. e256

Author(s):

E. Dushina ◽

Y. Barmenkova ◽

M. Lukyanova ◽

A. Golubeva ◽

N. Burko ◽

...

Keyword(s):

Heart Rate ◽

Autonomic Regulation ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Lowering Therapy ◽

Highly Effective ◽

Postinfarction Remodeling

Download Full-text

Role of Anti-PCSK9 Antibodies in the Treatment of Patients with Statin Intolerance

Current Medicinal Chemistry ◽

10.2174/0929867324666170616111647 ◽

2018 ◽

Vol 25 (13) ◽

pp. 1538-1548 ◽

Cited By ~ 4

Author(s):

Julia Schreml ◽

Ioanna Gouni-Berthold

Keyword(s):

Lipid Lowering ◽

Alternative Form ◽

Atherosclerotic Cardiovascular Disease ◽

Lipid Lowering Therapy ◽

Statin Intolerance ◽

Similar Frequency ◽

Definitive Answer ◽

Lowering Therapy ◽

Number Of Patients

Statin intolerance is usually defined as the inability of a patient to tolerate statintreatment due to muscle-related complaints. While randomised trials show that these complaints occure with similar frequency in patients receiving placebo, namely in up to ~5% of the subjects, and data from registries as well as clinical experience indicate a much higher frequency of up to ~30%. The lack of standard definition or of a diagnostic marker of statin intolerance confounds the problem. The diagnosis remains subjective based on the symptoms the patient reports. Therefore, a large number of patients who need a statin are not receiving it, or receiving only very-low and/or intermittent doses unable to achieve a robust decrease in low-density lipoprotein cholesterol (LDL-C), leaving patients at high or very high risk for cardiovascular events requiring an alternative form of lipid-lowering therapy. Until recently, the only available alternatives were niacin, ezetimibe, bile-acid sequestrants and fibrates that decrease LDL-C concentrations by up to 15-20%. Recently the fully human monoclonal antibodies against proprotein convertase subtilisin/kexin 9 (PCSK9), alirocumab (Praluent®) and evolocumab (Repatha®), which have been shown to decrease LDL-C by up to 70% have been approved in Europe for use in patients with primary hypercholesterolemia not at LDL-C target while on maximally tolerated lipid-lowering therapy and specifically for patients with statin intolerance and in the USA for patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia requiring additional LDL-C lowering. Ongoing large clinical trials with cardiovascular endpoints will provide a definitive answer for the role of anti-PCSK9 antibodies in clinical practice.

Download Full-text

Statin Intolerance: Diagnosis and Management

Indian Journal of Cardiovascular Disease in Women WINCARS ◽

10.1055/s-0037-1607193 ◽

2017 ◽

Vol 02 (03) ◽

pp. 014-020

Author(s):

Roopali Khanna ◽

Dandu Himanshu

Keyword(s):

Adverse Effects ◽

Clinical Symptoms ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Statin Intolerance ◽

Artery Disease ◽

Statin Dose

AbstractStatins are the main cornerstone in the treatment of coronary artery disease. Statins not only reduce the cardiovascular events but also significantly reduce the all-cause mortality. Due to adverse effects of statins, 20 to 30% of patients discontinue statins without consulting the physician. Most common adverse effects reported are muscle symptoms. Studies have shown that the majority of these patients can tolerate statin upon rechallenge. Alternative statin dosing, alternate-day statin, or twice-weekly statin dosing are different strategies to be given before changing to nonstatin lipid-lowering therapy. The newer nonstatin lipid-lowering drugs (ezetimibe, PCSK9 inhibitors) can be added if the low-density lipoprotein (LDL) target level can be achieved despite the maximally tolerated statin dose. This article reviews the etiology, clinical symptoms, and management of statin intolerance.

Download Full-text