Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity Score-Matched Nationwide Cohort Study.

BACKGROUND: This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19). METHODS: We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included. Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration. RESULTS: Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74-0.98) and PPI users (OR, 0.62; 95% CI, 0.52-0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52-1.54) or PPI users (OR, 1.22; 95% CI, 0.60-2.51). CONCLUSION: H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.

Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022. No language restrictions were applied. This study was registered in PROSPERO (CRD42021293218) prior to completing the literature search. Study Selection Two blinded reviewers assessed studies for inclusion. Eligible studies were randomized controlled trials in adults that compared berberine versus placebo, and measured blood lipids or lipoproteins. Data Extraction and Synthesis Data extraction was performed by two blinded reviewers using a structured form in Covidence. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Mean differences (MD) were estimated using inverse variance weighting with random effects models for lipid outcomes using R. Adverse events (AEs) were described narratively. Main Outcomes Primary outcomes were low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B. Secondary outcomes were gastrointestinal and muscle-related AEs. RESULTS: Eighteen studies (n = 1788 participants), conducted mainly in mainland China and Hong Kong (15 studies [83%]), were included with treatment durations ranging from 4 to 24 weeks. Berberine reduced LDL cholesterol (- 0.46 mmol/L, 95% CI - 0.62 to - 0.30, 14 studies, n = 1447), total cholesterol (- 0.48 mmol/L, 95% CI - 0.63 to - 0.33, 17 studies, n = 1637), triglycerides (- 0.34 mmol/L, 95% CI - 0.46 to - 0.23, 18 studies, n = 1661) and apolipoprotein B (- 0.25 g/L, 95% CI - 0.40 to - 0.11, 2 studies, n = 127). Berberine increased HDL cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.11, 15 studies, n = 1471). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (- 0.07 mmol/L, 95% CI - 0.16 to 0.02). Among 16 studies that reported AEs, no serious AEs were reported for berberine. Gastrointestinal AEs were reported in 12 studies and tended to be more frequent in participants allocated to berberine versus placebo (2-23% vs 2-15%). CONCLUSIONS: Berberine produces small reductions in LDL cholesterol, triglycerides, and apolipoprotein B, with potential sex-specific effects on HDL cholesterol. Large-scale trials that consider sex disparity and assess clinical outcomes are required.

Berberine is found naturally in barberry and goldenthread, plants which have long been used in traditional herbal medicine in Asia. Nowadays berberine is used as a purified product and is easy to purchase as a nutraceutical supplement or non-prescription drug. People with dyslipidemia, a medical condition often known as 'high cholesterol', may prefer treatment with a nutraceutical such as berberine to reduce blood cholesterol. In recent years, many studies have contrasted the effects of taking berberine with an inactive placebo. This study aimed to combine all the available randomized controlled trials that assessed berberine's effects on blood lipids and lipoproteins. We included 18 studies that used berberine doses of 900­1500 mg/day, the majority of which were conducted in mainland China and Hong Kong. We found that on average berberine can modestly reduce low-density lipoprotein (LDL) cholesterol by 0.5 mmol/L (18 mg/dL) and triglycerides by 0.3 mmol/L (30 mg/dL). Berberine also increases high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (2 mg/dL). Interestingly, women may obtain a greater increase in HDL cholesterol than men. The short-term use of berberine appears to be safe. No study participants treated with berberine experienced a serious adverse event. However, berberine may occasionally cause constipation, diarrhea, or nausea. Larger high-quality studies are still needed to determine the long-term effects of berberine for dyslipidemia.

TIMES TO ACT. Italian-Spanish-Polish-Uzbek Expert Forum Position Paper 2022. Dyslipidemia and arterial hypertension: The two most important and modifiable risk factors in clinical practice.

Hypertension and lipid disorders are two of the main cardiovascular risk factors. Both risk factors - if detected early enough - can be controlled and treated with modern, effective drugs, devoid of significant side effects, available in four countries as different as Italy, Spain, Poland, and Uzbekistan. The aim herein, was to develop this TIMES TO ACT consensus to raise the awareness of the available options of the modern and intensified dyslipidemia and arterial hypertension treatments. The subsequent paragraphs involves consensus and discussion of the deleterious effects of COVID-19 in the cardiovascular field, the high prevalence of hypertension and lipid disorders in our countries and the most important reasons for poor control of these two factors. Subsequently proposed, are currently the most efficient and safe therapeutic options in treating dyslipidemia and arterial hypertension, focusing on the benefits of single-pill combination (SPCs) in both conditions. An accelerated algorithm is proposed to start the treatment with a PCSK9 inhibitor, if the target low-density-lipoprotein values have not been reached. As most patients with hypertension and lipid disorders present with multiple comorbidities, discussed are the possibilities of using new SPCs, combining modern drugs from different therapeutic groups, which mode of action does not confirm the "class effect". We believe our consensus strongly advocates the need to search for patients with cardiovascular risk factors and intensify their lipid-lowering and antihypertensive treatment based on SPCs will improve the control of these two basic cardiovascular risk factors in Italy, Spain, Poland and Uzbekistan.

Black pepper oil (Piper nigrum L.) mitigates dexamethasone induced pancreatic damage via modulation of oxidative and nitrosative stress.

Dexamethasone acts as an immunosuppressive drug and has been used recently in the management of specific coronavirus disease 2019 (COVID-19) cases; however, various adverse effects could limit its use. In this work, we studied the mitigation effects of black pepper oil (BP oil) on glycemic parameters, dyslipidemia, oxidative and nitrosative stress and pancreatic fibrosis in dexamethasone-treated rats. Animals were divided into five groups that were treated with vehicle, dexamethasone (10 mg/kg, SC) or black pepper oil (BP oil, 0.5 mL, or 1 mL/kg) or metformin (50 mg/kg) plus dexamethasone for 4 consecutive days. Serum insulin, blood glucose, total cholesterol, triglycerides, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were higher in the dexamethasone group vs the control group and decreased in BP oil and metformin groups relative to the dexamethasone group. Pancreatic nitric oxide, inducible nitric oxide synthase and malondialdehyde levels were increased in the dexamethasone group vs the control group and decreased in BP oil and metformin groups relative to the dexamethasone group. Pancreatic endothelial nitric oxide synthase and reduced glutathione were declined in the dexamethasone group vs the control group. They were increased in BP oil and metformin groups relative to the dexamethasone group. Moreover, the pancreatic islets diameter and collagen deposition were assessed and found to be higher in the dexamethasone group vs the control group. BP oil and metformin groups showed to regress this effect. In conclusion, BP oil may alleviate hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia and pancreatic structural derangements and fibrosis by suppressing oxidative stress, increasing endogenous antioxidant levels, modulating nitric oxide signaling, preventing pancreatic stellate cells transition and collagen deposition.

The impact of obesity and dyslipidemia on Remdesivir effectiveness in hospitalized patients with SARS-CoV-2-related pneumonia: An observational study.

BACKGROUND AND AIMS: Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on Remdesivir effectiveness among hospitalized COVID-19 patients. METHODS AND RESULTS: We conducted an observational study on patients with SARS-CoV-2-related pneumonia admitted between May 2020 and September 2021 to the COVID-19 Units of Internal Medicine, Pneumology and Intensive Care of Garibaldi Hospital, Catania, Italy, and treated with Remdesivir. The "Ordinal Scale For Clinical Improvement" was used to assess patients' clinical improvement within 28 days of hospitalization. Short-term mortality rate was also evaluated. A total of 142 patients with SARS-CoV-2-related pneumonia were studied. The prevalence of obesity (20.7% vs. 41.9%, p = 0.03), the average BMI (27.1 ± 4.4 vs. 31.1 ± 6.1, p < 0.01) and the mean LDL-C levels (78 ± 19 mg/dl vs. 103 ± 18 mg/dl, p = 0.03) were significantly lower in early-improved (EI) compared to not-improved (NI) individuals. Obesity was negatively associated to clinical improvement after Remdesivir (OR 0.48, 95%CI 0.17-0.97, p = 0.04). Both obesity (OR 2.82, 95% CI 1.05-7.71, p = 0.04) and dyslipidemia (OR 2.78, 95%CI 1.17-7.16, p = 0.03) were significantly related to patients' mortality. Dyslipidemic subjects experienced a slower clinical improvement than non-dyslipidemic ones (Long-Rank p = 0.04). CONCLUSION: Our study showed that unfavorable metabolic conditions such as obesity and dyslipidemia could predict a worse clinical response to Remdesivir as well as the mortality in hospitalized COVID-19 patients. Further prospective and larger-scale studies are needed to confirm these preliminary findings.

Cardiovascular prevention: early and consistent prevention versus late intervention, complex approach to the treatment of modifiable risk factors: hypertension and dyslipidemia.

Cardiovascular diseases (not including COVID-19 infection) are still one of the most common causes of mortality and morbidity in our country and in developed countries. Today no one questions the intervention of all risk factors for atherosclerosis after a cardiovascular event, although unfortunately even in this case the recommended target values are often not achieved. However, the intervention of risk factors in primary prevention is often neglected. Atherosclerosis is a long-term process, developing since the childhood. It is a continuous process and the event itself is only the culmination of this process. Therefore, it is necessary to intervene in key risk factors early in life, and we have ample evidence that even early pharmacological intervention has a clear effect on slowing or stopping the process of atherosclerosis.

Association between Statin Use and Poor Outcomes in COVID-19 Patients with Diabetes Mellitus: A Systematic Review.

BACKGROUND AND AIMS: Diabetes mellitus, cardiovascular diseases, obesity, and dyslipidaemia are considered risk factors for more severe forms of COVID-19 infection. Statins have been widely used in such patients to prevent the occurrence of cardiovascular events and the associated mortality. However, statin use has been suggested to promote a more severe form of infection. This review aims to investigate the association between statin use and poor outcomes in COVID-19 patients with diabetes. METHODS: Literature search was performed in PubMed, CENTRAL, Scopus, and pre-print databases (MedRxiv and BioRxiv), and studies published up to March 6th, 2021 have been reviewed. Selected studies were then assessed for risk of bias with the Newcastle Ottawa Scale. RESULT: Four studies were included in the final analysis; all were retrospective studies. Two studies reported a decreased risk of mortality with statin use, while one study reported opposite findings. The other one did not find a significant association between statin use and poor COVID-19 outcomes. CONCLUSION: Available data suggest that statins may be safely administered to diabetic COVID-19 patients as the majority of evidence signifies statins to confer benefits and improve clinical outcomes in COVID-19 patients.

Updated Recommendations on Cardiovascular Prevention in 2022: An Executive Document of the Italian Society of Cardiovascular Prevention.

This executive document reflects and updates the key points of a Consensus document on Cardiovascular (CV) Prevention realized through the contribution of a number of Italian Scientific Societies and coordinated by the Italian Society of Cardiovascular Prevention (SIPREC). The aim of this executive document is to analyze and discuss the new recommendations introduced by international guidelines for the management of major CV risk factors, such as hypertension, dyslipidemias and type 2 diabetes, consisting in the identification of lower therapeutic targets, in the promotion of combination fixed drug therapies and in the introduction in routine clinical practice of new effective pharmacological classes. Moreover, the document highlights the importance of effective CV prevention strategies during the the coronavirus disease 2019 (COVID-19) outbreak which has dramatically changed the priorities and the use of available resources by the national healthcare systems and have caused a reduction of programmed follow-up visits and procedures and even of hospital admissions for severe acute pathologies. In addition, the pandemic and the consequent lockdown measures imposed have caused a widespread diffusion of unhealthy behaviors with detrimental effects on the CV system. In such a context, reinforcement of CV prevention activities may play a key role in reducing the future impact of these deleterious conditions.

Association of Statins and 28-Day Mortality Rates in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated). METHODS: In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission. RESULTS: Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old. CONCLUSION: Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.

COVID-19 and lipids. The role of lipid disorders and statin use in the prognosis of patients with SARS-CoV-2 infection.

The global coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 coronavirus started in March 2020. The conclusions from numerous studies indicate that people with comorbidities, such as arterial hypertension, diabetes, obesity, underlying cardiovascular disease, are particularly vulnerable to the severe course of COVID-19. The available data also suggest that patients with dyslipidemia, the most common risk factor of cardiovascular diseases, are also at greater risk of severe course of COVID-19. On the other hand, it has been shown that COVID-19 infection has an influence on lipid profile leading to dyslipidemia, which might require appropriate treatment. Owing to antiviral, anti-inflammatory, immunomodulatory, and cardioprotective activity, statin therapy has been considered as valuable tool to improve COVID-19 outcomes. Numerous observational studies have shown potential beneficial effects of lipid-lowering treatment on the course of COVID-19 with significant improved prognosis and reduced mortality.

Preadmission Statin Therapy and Clinical Outcome in Hospitalized Patients With COVID-19: An Italian Multicenter Observational Study.

ABSTRACT: Statin therapy has been recently suggested as possible adjuvant treatment to improve the clinical outcome in patients with coronavirus disease 2019 (COVID-19). The aim of this study was to describe the prevalence of preadmission statin therapy in hospitalized patients with COVID-19 and to investigate its potential association with acute distress respiratory syndrome (ARDS) at admission and in-hospital mortality. We retrospectively recruited 467 patients with laboratory-confirmed COVID-19 admitted to the emergency department of 10 Italian hospitals. The study population was divided in 2 groups according to the ARDS diagnosis at admission and in-hospital mortality. A multivariable regression analysis was performed to assess the risk of ARDS at admission and death during hospitalization among patients with COVID-19. A competing risk analysis in patients taking or not statins before admission was also performed. ARDS at admission was reported in 122 cases (26.1%). There was no statistically significant difference for clinical characteristics between patients presenting with and without ARDS. One hundred seven patients (18.5%) died during the hospitalization; they showed increased age (69.6 ± 13.1 vs. 66.1 ± 14.9; P = 0.001), coronary artery disease (23.4% vs. 12.8%; P = 0.012), and chronic kidney disease (20.6% vs. 11.1%; P = 0.018) prevalence; moreover, they presented more frequently ARDS at admission (48.6% vs. 19.4%; P < 0.001). At multivariable regression model, statin therapy was not associated neither with ARDS at admission nor with in-hospital mortality. Preadmission statin therapy does not seem to show a protective effect in severe forms of COVID-19 complicated by ARDS at presentation and rapidly evolving toward death.

Central blood pressure lowering effect of telmisartan-rosuvastatin single-pill combination in hypertensive patients combined with dyslipidemia: A pilot study.

This multicenter, phase 4, Prospective Randomized Open, Blinded End-point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single-pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID-19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10-year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4-week single-group run-in period with telmisartan 40-80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial-ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between-group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between-group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between-group difference p = .078). Change of AIx had no significant difference (between-group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.

Assessing forgetfulness and polypharmacy and their impact on health-related quality of life among patients with hypertension and dyslipidemia in Greece during the COVID-19 pandemic.

PURPOSE: We estimate the association between forgetfulness to take medications as prescribed and polypharmacy and health-related quality of life (HRQoL) among a cohort of patients with hypertension, dyslipidemia or both in Greece during the COVID-19 pandemic. METHODS: A telephone survey of 1018 randomly selected adults was conducted in Greece in June 2020. Participants were included in the survey, if they (a) had a diagnosis of hypertension, dyslipidemia or both and (b) were on prescription treatment for these conditions. HRQoL was calculated using the short form (SF) -12 Patient Questionnaire. A multivariable generalized linear regression model (GLM) was used to estimate the association between forgetfulness and polypharmacy and HRQoL, controlling for sociodemographic and health-related covariates. RESULTS: Overall, 351 respondents met the inclusion criteria, of whom 28 did not fully complete the questionnaire (response rate: 92%, n = 323). Of those, 37% were diagnosed with hypertension only, 28% with dyslipidemia only, and 35% with both. Most reported good to average physical (64.1%) and mental health (48.6%). Overall, 25% indicated that they sometimes forget to take their prescribed medications, and 12% took two or more pills multiple times daily. Total HRQoL score was 68.9% (s.d. = 18.0%). About 10% of participants reported paying less attention to their healthcare condition during the pandemic. Estimates of multivariable analyses indicated a negative association between forgetfulness (- 9%, adjusted ß: - 0.047, 95% confidence interval - 0.089 to - 0.005, p = 0.029), taking two or more pills multiple times daily compared to one pill once a day (- 16%, adjusted ß: - 0.068, 95% confidence interval - 0.129 to - 0.008, p = 0.028) and total HRQoL. CONCLUSION: Our results suggest that among adult patients with hypertension, dyslipidemia or both in Greece, those who forget to take their medications and those with more complex treatment regimens had lower HRQoL. Such patients merit special attention and require targeted approaches by healthcare providers to improve treatment compliance and health outcomes.

The impact of atherosclerotic cardiovascular disease, dyslipidaemia and lipid lowering therapy on Coronavirus disease 2019 outcomes: an examination of the available evidence.

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.

Association Between Statin Use Prior to Admission and Lower Coronavirus Disease 2019 (COVID-19) Severity in Patients With Cardiovascular Disease or Risk Factors.

BACKGROUND: Cardiovascular diseases and/or risk factors (CVDRF) have been reported as risk factors for severe coronavirus disease 2019 (COVID-19).Methods and Results:In total, we selected 693 patients with CVDRF from the CLAVIS-COVID database of 1,518 cases in Japan. The mean age was 68 years (35% females). Statin use was reported by 31% patients at admission. Statin users exhibited lower incidence of extracorporeal membrane oxygenation (ECMO) insertion (1.4% vs. 4.6%, odds ratio [OR]: 0.295, P=0.037) and septic shock (1.4% vs. 6.5%, OR: 0.205, P=0.004) despite having more comorbidities such as diabetes mellitus. CONCLUSIONS: This study suggests the potential benefits of statins use against COVID-19.

Role of Statins in Coronavirus-Related Disease (COVID-19): A Retrospective Cohort Study in Northern Italy.

INTRODUCTION: The outbreak by SARS-CoV-2 has rapidly spread worldwide. The need for specific treatments to adequately stop the inflammatory response and its sequelae is day by day more urgent and many therapeutic strategies were performed since COVID-19 burst in the last months. Statins were thought to be effective against this novel coronavirus for their anti-inflammatory properties, even if the real effects on COVID patients are still partially unexplored. METHODS: We retrospectively evaluated 501 adult patients, consecutively admitted to the two COVID-hospitals of Ferrara's territory, and divided them into two groups: ST = patients on statin therapy on admission and NST=patients not on statin therapy on admission. We searched for differences between groups in terms of anamnestic, clinical and laboratory data and then in terms of COVID-19 outcomes. RESULTS: We found significant differences between groups in terms of age, comorbidities, procalcitonin and CPK serum levels: ST patients were older, more comorbid, with lower procalcitonin and higher CPK serum levels. Male sex was, together with the Charlson Comorbidity Index, an independent predictor of needing intensification of care, while age only was a good predictor of in-hospital and 100-day mortality. Differences were also found in the survival functions between the two groups. CONCLUSIONS: After a period of observation of 100 days, ST patients, despite their older age and their greater load of comorbidities, have similar survival functions to NST patients. If adjusted for age and CCI the survival functions of ST group are considerably more favourable than those of the second group.

Inclisiran: First Approval.

Inclisiran (Leqvio®; Novartis) is a first-in-class, cholesterol-lowering small interfering RNA (siRNA) conjugated to triantennary N-acetylgalactosamine carbohydrates (GalNAc). Inclisiran received its first approval in December 2020 in the EU for use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet. It is intended for use in combination with a statin or a statin with other lipid-lowering therapies in patients unable to reach low-density lipoprotein cholesterol goals with the maximum tolerated statin dose. In patients who are statin-intolerant or for whom a statin is contraindicated, inclisiran can be used alone or in combination with other lipid-lowering therapies. Inclisiran is administered as a twice-yearly subcutaneous injection. This article summarizes the milestones in the development of inclisiran leading to this first approval for primary hypercholesterolaemia or mixed dyslipidaemia.

Association of Pre-Admission Statin Use With Reduced In-Hospital Mortality in COVID-19.

BACKGROUND: Coronavirus disease-19 (COVID-19) infection is associated with an uncontrolled systemic inflammatory response. Statins, given their anti-inflammatory properties, may reduce the associated morbidity and mortality. This study aimed to determine the association between statin use prior to hospitalization and in-hospital mortality in COVID-19 patients. METHODS: In this retrospective study, clinical data were collected from the electronic medical records of patients admitted to the hospital with confirmed COVID-19 infection from March 1, 2020 to April 24, 2020. A multivariate regression analysis was performed to study the association of pre-admission statin use with in-hospital mortality. RESULTS: Of 255 patients, 116 (45.5%) patients were on statins prior to admission and 139 (54.5%) were not. The statin group had a higher proportion of end stage renal disease (ESRD) (13.8% vs. 2.9%, p = 0.001), diabetes mellitus (63.8% vs. 35.2%, p<0.001), hypertension (87.9% vs. 61.1%, p < 0.001) and coronary artery disease (CAD) (33.6% vs. 5%, p < 0.001). On multivariate analysis, we found a statistically significant decrease in the odds of in-hospital mortality in patients on statins before admission (OR 0.14, 95% CI 0.03- 0.61, p = 0.008). In the subgroup analysis, statins were associated with a decrease in mortality in those with CAD (OR 0.02, 95% CI 0.0003-0.92 p = 0.045) and those without CAD (OR 0.05, 95% CI 0.005-0.43, p = 0.007). CONCLUSIONS: Our study suggests that statins are associated with reduced in-hospital mortality among patients with COVID-19, regardless of CAD status. More comprehensive epidemiological and molecular studies are needed to establish the role of statins in COVID-19.

Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression.

AIMS: One of the comorbidities associated with severe outcome and mortality of COVID-19 is dyslipidemia. Statin is one of the drugs which is most commonly used for the treatment of dyslipidemic patients. This study aims to analyze the association between statin use and composite poor outcomes of COVID-19. DATA SYNTHESIS: We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until November 25th, 2020. All articles published on COVID-19 and statin were retrieved. Statistical analysis was done using Review Manager 5.4 and Comprehensive Meta-Analysis 3 software. RESULTS: A total of 35 studies with a total of 11, 930, 583 patients were included in our analysis. Our meta-analysis showed that statin use did not improve the composite poor outcomes of COVID-19 [OR 1.08 (95% CI 0.86-1.35), p = 0.50, I2 = 98%, random-effect modelling]. Meta-regression showed that the association with composite poor outcomes of COVID-19 was influenced by age (p = 0.010), gender (p = 0.045), and cardiovascular disease (p = 0.012). Subgroup analysis showed that the association was weaker in studies with median age ≥60 years-old (OR 0.94) compared to <60 years-old (OR 1.43), and in the prevalence of cardiovascular disease ≥25% (RR 0.94) compared to <25% (RR 1.24). CONCLUSION: Statin use did not improve the composite poor outcomes of COVID-19. Patients with dyslipidemia should continue taking statin drugs despite COVID-19 infection status, given its beneficial effects on cardiovascular outcomes.