Improved COVID-19 Outcomes following Statin Therapy: An Updated Systematic Review and Meta-analysis

Background. Although vaccine rollout for COVID-19 has been effective in some countries, there is still an urgent need to reduce disease transmission and severity. We recently carried out a meta-analysis and found that pre- and in-hospital use of statins may improve COVID-19 mortality outcomes. Here, we provide an updated meta-analysis in an attempt to validate these results and increase the statistical power of these potentially important findings. Methods. The meta-analysis investigated the effect of observational and randomized clinical studies on intensive care unit (ICU) admission, tracheal intubation, and death outcomes in COVID-19 cases involving statin treatment, by searching the scientific literature up to April 23, 2021. Statistical analysis and random effect modeling were performed to assess the combined effects of the updated and previous findings on the outcome measures. Findings. The updated literature search led to the identification of 23 additional studies on statin use in COVID-19 patients. Analysis of the combined studies ( n = 47 ; 3,238,508 subjects) showed no significant effect of statin treatment on ICU admission and all-cause mortality but a significant reduction in tracheal intubation ( OR = 0.73 , 95% CI: 0.54-0.99, p = 0.04 , n = 10 studies). The further analysis showed that death outcomes were significantly reduced in the patients who received statins during hospitalization ( OR = 0.54 , 95% CI: 0.50-0.58, p < 0.001 , n = 7 studies), with no such effect of statin therapy before hospital admission ( OR = 1.06 , 95% CI = 0.82 -1.37, p = 0.670 , n = 29 studies). Conclusion. Taken together, this updated meta-analysis extends and confirms the findings of our previous study, suggesting that in-hospital statin use leads to significant reduction of all-cause mortality in COVID-19 cases. Considering these results, statin therapy during hospitalization, while indicated, should be recommended.

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Influence of Statin Therapy on the Incidence of Cardiovascular Events, Cancer, and All-Cause Mortality in People Living With HIV: A Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.769740 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yanping Li ◽

Zhandi Wang ◽

Haimei Xia ◽

Ju Zhang

Keyword(s):

Cohort Studies ◽

Statin Therapy ◽

Cardiovascular Events ◽

Meta Analysis ◽

People Living With Hiv ◽

All Cause Mortality ◽

Living With Hiv ◽

Risk Of Cancer ◽

Reduced Risk ◽

Statin Use

Background: Possible influences of statin therapy on the risk of cardiovascular events, cancer, and all-cause mortality in people living with HIV (PLWH) remain unclear. We performed a meta-analysis to systematically evaluate the efficacy of statin in PLWH.Methods: Relevant cohort studies were retrieved via a search of the Medline, the Embase, and the Web of Science databases until June 14, 2021. The data were combined with a random-effects model by incorporating the between-study heterogeneity.Results: A total of 12 multivariate cohort studies with 162,252 participants were eligible for the meta-analysis and 36,253 (22.3%) of them were statin users. Pooled results showed that statin use was independently related to a reduced mortality risk in PLWH [adjusted risk ratio (RR): 0.56, 95% CI: 0.44 to 0.72, p < 0.001, I2 = 41%]. In addition, results of the meta-analysis showed that statin use was not significantly associated with a reduced risk of cardiovascular events in PLWH compared to the statin non-users (RR: 1.14, 95% CI: 0.80 to 1.63, p = 0.48, I2 = 42%). However, statin use was significantly related to a reduced risk of cancer in PLWH (RR: 0.73, 95% CI: 0.58 to 0.93, p = 0.009, I2 = 49%). Sensitivity analyses by excluding one study at a time showed consistent results. No significant publication biases were observed.Conclusion: Statin use is associated with reduced all-cause mortality in PLWH. In addition, statin use is related to a reduced risk of cancer, although the risk of cardiovascular events seems not significantly affected.

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Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Critical Care ◽

10.1186/s13054-021-03540-6 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Eleni Papoutsi ◽

Vassilis G. Giannakoulis ◽

Eleni Xourgia ◽

Christina Routsi ◽

Anastasia Kotanidou ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Meta Analysis ◽

Mortality And Morbidity ◽

Icu Admission ◽

All Cause Mortality ◽

Detectable Difference

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

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Preoperative statin therapy is associated with reduced 30-day postoperative all-cause mortality in patients undergoing coronary artery bypass surgery: A meta-analysis of large size observational studies

International Journal of Cardiology ◽

10.1016/j.ijcard.2014.11.216 ◽

2015 ◽

Vol 181 ◽

pp. 11-13 ◽

Cited By ~ 3

Author(s):

Jiayang Wang ◽

Chengxiong Gu ◽

Mingxin Gao ◽

Wenyuan Yu ◽

Yang Yu

Keyword(s):

Coronary Artery ◽

Statin Therapy ◽

Coronary Artery Bypass ◽

Observational Studies ◽

Coronary Artery Bypass Surgery ◽

Bypass Surgery ◽

Meta Analysis ◽

Artery Bypass ◽

Large Size ◽

All Cause Mortality

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Abstract 12188: Intensive Glycemic Control in Patients With Acute Coronary Syndrome: Evidence From a Meta-Analysis

Circulation ◽

10.1161/circ.130.suppl_2.12188 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Partha Sardar ◽

Ramez Nairooz ◽

Saurav Chatterjee ◽

Jacob A Udell ◽

Dharam J Kumbhani ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Glycemic Control ◽

Meta Analysis ◽

Random Effect ◽

Intensive Glucose Control ◽

Intensive Glycemic Control ◽

Coronary Syndrome ◽

All Cause Mortality ◽

Glucose Management ◽

Management Groups

Introduction: Hyperglycemia is associated with unfavorable prognosis in patients with acute coronary syndrome (ACS). Studies with intensive glycemic control in ACS patients have provided inconsistent results. A meta-analysis was performed to evaluate the effectiveness and safety of intensive glycemic control in patients with ACS. Methods: Search of PubMed, Cochrane CENTRAL, EMBASE, EBSCO, Web of Science and CINAHL databases from their inception through April 2014, identifying randomized controlled trials (RCTs) comparing the effects of intensive versus standard glucose management in patients with ACS. We calculated summary random-effect odds ratios (OR) and 95% confidence intervals (CI). Results: Results from 10 RCTs comprising 2,621 patients were analyzed. All-cause mortality between intensive versus standard glucose management groups did not differ significantly (OR 1.00, 95% CI 0.75-1.34). Similarly, no significant differences were observed between the comparator groups for the odds of cardiac mortality (OR 0.87, 95% CI, 0.67 to 1.12), recurrent myocardial infarction (OR 1.07, 95% CI, 0.76 to 1.52), or stroke (OR 1.20, 95% CI, 0.60 to 2.40). The risk of hypoglycemia (OR 5.95, 95% CI, 2.73 to 12.97; p<0.001) was significantly higher with intensive compared with standard glucose management. Conclusions: Intensive glucose control compared with standard care in ACS patients did not reduce mortality or morbidity, but significantly increased the risk of hypoglycemia. These data from prior clinical trials should be interpreted in the context of their significant methodological limitations.

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Abstract 2211: Statin Therapy May Increase the Risk of Intracerebral Hemorrhage: A Meta-analysis of 26 Randomized Controlled Trials

Stroke ◽

10.1161/str.43.suppl_1.a2211 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

James S McKinney ◽

William J Kostis ◽

John B Kostis

Keyword(s):

Statin Therapy ◽

Meta Analysis ◽

Active Group ◽

Controlled Trials ◽

Control Groups ◽

Randomized Controlled ◽

All Cause Mortality ◽

Group A ◽

The Difference ◽

And Control

Introduction--- Statin therapy decreases the risk of myocardial infarction and ischemic stroke. However, an increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue we performed a meta-analysis of all randomized controlled trials (RCTs) using statins that reported ICH. Methods--- We performed a Medline literature search through March 18, 2011 and identified additional RCTs by reviewing reference lists of retrieved studies and prior meta-analyses. All RCTs of statin therapy versus placebo or high dose versus low dose statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. 26 RCTs were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results--- 84 831 subjects were included in the Active group, and 84 851 in the Control group. A trend towards a higher incidence of ICH was observed in the Active treatment group compared to Control (OR = 1.15; 95% CI = 0.91 to 1.45, p =0.24) (Figure). Significant relationships were not observed between the log OR for ICH with achieved LDL in the Active group (slope = 0.0002; 95% CI = -0.0098 to 0.0101, p =0.96) or with the difference in LDL drop between the Active and Control groups (slope = 0.0030; 95% CI = -0.0089 to 0.0149, p =0.62). Total stroke (OR = 0.84; 95% CI = 0.78 to 0.91, p <0.001) and all-cause mortality (OR = 0.91; 95% CI = 0.86 to 0.96, p <0.001) were significantly reduced in the Active group. A significant relationship between all-cause mortality and the difference in LDL drop between the Active and Control groups was observed (slope = -0.0030; 95% CI = -0.0009 to -0.0051, p<0.005). There was not evidence of publication bias in this meta-analysis. Conclusions--- Active therapy was associated with a trend towards increased ICH in this meta-analysis of 26 RCTs of statin therapy. However, this risk does not appear to be related to the degree of decline or achieved LDL. The risk of ICH is offset by a significant reduction in ischemic stroke and all-cause mortality and should not dissuade practitioners from prescribing statins in otherwise appropriate patients.

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Abstract TP439: Statin Treatment and Prevalent Cerebral Microbleeds: A Systematic Review and Meta-Analysis

Stroke ◽

10.1161/str.51.suppl_1.tp439 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Aristeidis H Katsanos ◽

Vasileios-Arsenios Lioutas ◽

Andreas Charidimou ◽

Luciana Catanese ◽

Kelvin K Ng ◽

...

Keyword(s):

Hemorrhagic Stroke ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Statin Treatment ◽

Cerebral Microbleeds ◽

Cross Sectional ◽

History Of ◽

Ancillary Studies ◽

Unadjusted Analysis ◽

Statin Use

Introduction: Statins have been reported to increase the risk of intracererbral hemorrhage, however their effects on cerebral microbleeds (CMBs) formation is not well understood. We systematically reviewed previously published studies to pool adjusted and unadjusted estimates of the association between prevalent CMBs and current statin use. Methods: We performed a systematic search in MEDLINE and SCOPUS databases on July 28 th , 2019 to identify all cohorts from randomized clinical trials or observational studies reporting CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Associations are reported as odds ratios (ORs) with corresponding 95% confidence intervals (95%CI). Random effects model was used to calculate the pooled estimates. Results: We included 7 studies (n=3671 participants): unselected general population [n=1965], ischemic stroke [n=770], hemorrhagic stroke [n=252], hypertension [n=605] or neuroimaging based studies [n=72]. Statin use was not associated with CMBs presence in either unadjusted (OR=1.15, 95%CI: 0.76-1.74) or adjusted analyses (OR=1.01, 95%CI: 0.62-1.64). Statin use was more strongly related to lobar CMB presence (OR=2.01, 95%CI: 1.48-2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR=2.26, 95%CI: 0.86-5.91). Except for the analysis on the unadjusted probability of CMBs presence, considerable heterogeneity was present in all other analyses (I 2 >60%). Conclusion: Our findings suggest that statin treatment is not associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.

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Efficacy of statin treatment based on cardiovascular outcomes in elderly patients: a standard meta-analysis and Bayesian network analysis

Journal of International Medical Research ◽

10.1177/0300060520926349 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052092634 ◽

Cited By ~ 2

Author(s):

Chuannan Zhai ◽

Kai Hou ◽

Rui Li ◽

YueCheng Hu ◽

JingXia Zhang ◽

...

Keyword(s):

Secondary Prevention ◽

Cardiovascular Mortality ◽

Cardiovascular Events ◽

Meta Analysis ◽

The Elderly ◽

Statin Treatment ◽

Comparative Effect ◽

Randomized Controlled ◽

All Cause Mortality ◽

Central Database

Objective Statins have been shown to be beneficial for the prevention of cardiovascular events. In elderly individuals, the efficacy of statins remains controversial and the comparative effect of statins has not been assessed. Methods MEDLINE, Embase, and the Cochrane Central database were searched for randomized controlled trials that assessed statins in older patients. Results Seventeen trials were analyzed. When used for secondary prevention, statins were associated with reduced risk of cardiovascular events, all-cause mortality, cardiovascular mortality, revascularization, and stroke. When used for primary prevention, statins reduced the risk of myocardial infarction and revascularization, but did not significantly affect other outcomes. A modest difference between pharmaceutical statin products was found, and high-quality evidence indicated that intensive atorvastatin had the greatest benefits for secondary prevention. Conclusions In secondary prevention, evidence strongly suggests that statins are associated with a reduction in the risk of all-cause mortality, cardiovascular events, cardiovascular mortality, and revascularization. However, differences in the effects of various statins do not appear to have significant effects on therapy in secondary prevention for the elderly.

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Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis

Annals of Pharmacotherapy ◽

10.1177/1060028020964451 ◽

2020 ◽

pp. 106002802096445

Author(s):

Enrica Di Martino ◽

Alessio Provenzani ◽

Patrizio Vitulo ◽

Piera Polidori

Keyword(s):

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

World Health ◽

Effect Model ◽

All Cause Mortality ◽

Positive Effect

Background: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. Objective: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. Methods: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization’s registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen’s d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). Results: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). Conclusion and Relevance: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.

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Aspirin Exposure and Mortality Risk among Prostate Cancer Patients: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2019/9379602 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Lai lai Fan ◽

Cheng Peng Xie ◽

Yi Ming Wu ◽

Xi jie Gu ◽

Ying he Chen ◽

...

Keyword(s):

Prostate Cancer ◽

Frequency Response ◽

Mortality Risk ◽

Meta Analysis ◽

Random Effect ◽

Response Analysis ◽

Dose Frequency ◽

All Cause Mortality ◽

Cancer Specific Mortality ◽

Random Effect Models

Background. Prostate cancer (PCa) is the ninth most common cause of cancer death globally. Many studies have investigated aspirin exposure and mortality risk among PCa patients, returning inconsistent results. We conducted a comprehensive meta-analysis to explore the association between aspirin exposure and mortality risk among PCa patients and to investigate potential dose/duration/frequency-response relationships. Methods and Results. Studies published from 1980 to 2018 of PubMed and EMBASE databases were searched. We included 14 studies with 110,000 participants. Multivariate-adjusted odds ratios (ORs) were pooled using random-effect models. Potential dose/duration/frequency-response relationships were evaluated for aspirin exposure and prostate cancer-specific mortality (PCSM) risk. We did not detect an association between the highest aspirin exposure and mortality risk (PCSM of prediagnostic aspirin exposure, OR: 0.96, 95% confidence interval [CI]: 0.87-1. 07, I2 = 0%; PCSM of postdiagnostic aspirin exposure, OR:0.92, 95% CI: 0.77-1.10, I2 = 56.9%; all-cause mortality [ACM] of prediagnostic aspirin exposure, OR: 0.96, 95% CI: 0.88-1.04, I2 = 9.4%; ACM of postdiagnostic aspirin exposure, OR: 0.95, 95% CI: 0.73-1.23, I2 = 88.9%). There was no significant dose/frequency-response association observed for aspirin exposure and PCSM risk. On duration-response analysis, we found that short-term postdiagnostic aspirin exposure (shorter than 2.5 years) increased the risk of PCSM. Conclusions. Our meta-analysis suggests that there is no association between aspirin exposure and PCSM risk. Nor is there an association between the highest aspirin exposure and ACM risk among PCa patients. More studies are needed for a further dose/duration/frequency-response meta-analysis.

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Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis

Lipids in Health and Disease ◽

10.1186/s12944-019-1135-z ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 2

Author(s):

Agata Bielecka-Dabrowa ◽

Ibadete Bytyçi ◽

Stephan Von Haehling ◽

Stefan Anker ◽

Jacek Jozwiak ◽

...

Keyword(s):

Heart Failure ◽

Clinical Outcomes ◽

Meta Analysis ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Patients With Heart Failure ◽

All Cause Mortality ◽

Meta Analyses ◽

Statin Use

Abstract Background The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. Methods We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. Results Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.

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