ABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates blood cholesterol levels by degrading low-density lipoprotein (LDL) receptors from the surface of hepatocytes. Studies have shown that inhibiting this molecule decreases the cardiovascular risk in individuals with atherosclerotic cardiovascular disease (ASCVD) by lowering low-density lipoprotein cholesterol (LDL-C). Two major cardiovascular outcome trials showed that the use of the PCSK9 inhibitors (alirocumab and evolocumab) in patients with recent acute coronary syndrome (ACS) is associated with a lower risk of further cardiovascular (CV) events. Information regarding the use of these monoclonal antibodies for primary prevention has also been reported by these trials. The goal of this systematic review is to describe the mechanism of PCSK9 inhibitors and further discuss their ability to reduce CV risk in high-risk populations. The search strategy was used in a systematic way using PubMed Central, Google Scholar, and ScienceDirect. We included randomized control trials (RCTs), systematic reviews, and narrative reviews in English published in the last five years. Observational studies, case reports, and case studies were excluded. The quality of the studies was evaluated using the Cochrane Collaboration Risk of Bias Tool, Assessment of Multiple Systematic Reviews 2, and Scale for the Assessment of Narrative Review Articles. A total of 10 articles were included in this systematic review. These included an RCT, a systematic review, and eight narrative reviews. Our study suggested that adding PCSK9 inhibitors to background statin therapy for selected patients with high-risk factors demonstrated substantial benefits in reducing overall CV morbidity and mortality after ACS. Multiple studies have demonstrated the short-term safety of low LDL-C levels caused by these drugs. However, long-term safety must be assessed with further studies.
ABSTRACT
Coronary artery disease (CAD) is one of the leading causes of death worldwide. Atherosclerosis begins in childhood as fatty streaks, progresses with age, and lifestyle influences the progression of atherosclerotic plaque. Over time, with significant narrowing of the blood vessels, blood flow into the coronary arteries is compromised, resulting in various symptoms of coronary heart disease. Many drugs are used in clinical practice to prevent atherosclerotic cardiovascular events in patients with CAD. This review aims to investigate the efficacy and safety of a non-statin novel lipid-lowering drug, bempedoic acid (BDA), an adenosine triphosphate (ATP) citrate lyase inhibitor, in lowering serum low-density lipoprotein cholesterol (LDL-C) levels among patients with CAD. BDA is a new drug that recently got approval for clinical use. Following its discovery, BDA has been researched in order to investigate its role in the treatment of hypercholesterolemia. A search for studies was conducted using databases such as PubMed, PMC, ScienceDirect, and Google Scholar up until April 30, 2022. This systematic review has followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 11 studies were finalized to explore the role of BDA alone or as an adjunct in lowering serum LDL-C levels in high-risk patients under maximally tolerated statins, statin-intolerant groups, or treatment with other lipid-lowering drugs. These studies are three randomized controlled trials (RCTs), one pre-proof RCT, two systematic reviews and meta-analyses, and five narrative review articles. This review included 8465 participants from recently conducted RCTs and systematic reviews. Another 14014 participants, enrolled for the Cholesterol Lowering via Bempedoic Acid, an Adenosine Triphosphate-Citrate Lyase-Inhibiting Regimen (CLEAR) Outcomes clinical trial, were also included. BDA in combination with ezetimibe showed good evidence of LDL-C lowering effect. Patients on maximally tolerated statin failing to achieve desired LDL-C when treated in combination with BDA showed a significant decrement in serum LDL-C levels, high sensitivity C-reactive protein (HsCRP), and triglyceride. BDA use showed no adverse side effects. The most common side effect seen in several trials was the rise in serum uric acid level. When treating patients with BDA, baseline uric acid levels should be obtained and regular monitoring of uric acid should be done. The CLEAR Outcomes trial, scheduled to be completed by December 2022, will provide further information on BDA. BDA appears to be a promising alternative to currently available secondary lipid-lowering agents.
ABSTRACT
A cystic fibrosis (CF) transmembrane conductor regulator (CFTR) gene modulating triple therapy combining elexacaftor-tezacaftor-ivacaftor (Trikafta) has been recently discovered. Its approval by the Food and Drug Administration (FDA) in 2019 has expanded the target therapy group to individuals aged twelve and up with at least one Phe508del (phenylalanine 508 deletion) mutation in the CFTR gene. This systematic review aims to assess this combination therapy's safety and efficacy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, an in-depth search was performed. The search was done by utilizing databases such as PubMed Central (PMC), Google Scholar, and Science Direct for articles related to this topic. Studies published in the last five years in the English language were chosen preliminarily. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias and finalize ten articles to be used in this review. The chosen articles constituted four randomized control trials (RCTs), four systematic reviews, and two narrative reviews. The last date for data collection was April 24, 2022. Based on the findings of this review, we concluded that by combining three CFTR modulators, this therapy had outperformed all the currently available medications in terms of improving pulmonary function, reducing exacerbations, and enhancing the quality of life of CF patients. In clinical trials, headache and rash were the most common side effects, and laboratory testing to assess liver function is suggested. Long-term safety and effectiveness must be confirmed by the continued review of real-life patient data. Studies done on triple therapy thus far have been promising. Unfortunately, a small proportion of the CF population remains ineligible for any form of CFTR modulator therapy owing to their type of genetic mutation, and this provides ground for further research in this field.
ABSTRACT
Migraine-a term used to describe a unilateral throbbing headache has shown growing evidence of being linked to different types of strokes-particularly ischemic and hemorrhagic. This study aims to identify and summarize the relationship between migraine and the incidents of stroke in women of child-bearing age. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was done using PubMed, the British Medical Journal (BMJ), Cochrane library, Google Scholar, and ScienceDirect databases up until March 15, 2022. Studies were chosen based on the listed eligibility criteria: English-language, observational studies, systematic reviews, articles, and meta-analyses, which included stroke patients and migraine patients, and the possible link between these two conditions. In addition, quality assessment was done using assessment tools like Scale for the Assessment of Narrative Review Articles (SANRA), Assessment of multiple systematic reviews (AMSTAR), and Newcastle-Ottawa Scale (NOS) criteria. The initial search generated 245 studies. Fourteen studies were included in the final selection - one case-control, four cohort studies, seven systematic reviews with meta-analyses, and two narrative reviews. Strokes-particularly ischemic-were found to be linked to the incidents of migraine in women. The risks of a stroke increased if a woman was a smoker, under 45, and uses oral contraceptives regularly. In addition, the use of nonsteroidal anti-inflammatory drugs (NSAIDs), genetic predisposition, and metabolic dysfunction was linked to increased incidents of hemorrhagic strokes-which proved to be rarer but more fatal due to their serious underlying pathophysiologies.
ABSTRACT
We conducted a systematic review to determine the efficacy and safety of cannabidiol (CBD) for chronic pain. The systematic review is according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 checklist. Five databases (PubMed, PubMed Central, Medline, Cochrane Library, and ScienceDirect) were searched using cannabidiol, CBD, hemp, and chronic pain. Inclusion criteria used were studies on adult populations >18 years old; pain symptoms >three months duration; all available preparations of CBD; human studies only; publication in English in the past five years. A total of 2298 articles were found. Inclusion criteria were applied, and quality assessments were done, resulting in 12 publications eligible for the review. CBD and tetrahydrocannabinol (THC), both from Cannabis plants with almost identical chemical structures, attach to the CB receptor, eliciting different effects like the psychoactivity seen on THC but less or none in CBD. Regulations of CBD worldwide differ from each other due to the insufficiency of solid evidence to establish its benefit versus the risks. However, a few studies are showing the benefits of CBD not only for chronic pain but also for sleep improvement and quality of life. In conclusion, CBD is an excellent alternative to an opioid in chronic pain because CBD is non-intoxicating in its pure form. More clinical trials should be done to prove CBD's significance clinically and statistically.
