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.

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, longterm safety must be assessed with further studies.