scholarly journals 13. The Efficacy and Effectiveness of Pneumococcal Vaccines against Pneumococcal Pneumonia among Adults: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S130-S131
Author(s):  
Lana Childs ◽  
Miwako Kobayashi ◽  
Jennifer Loo Farrar ◽  
Tamara Pilishvili
Keyword(s):  
Systematic Review ◽  
Study Design ◽  
Observational Studies ◽  
Pneumococcal Pneumonia ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Pneumococcal Vaccines ◽  
Random Effects Models ◽  
Vaccine Type ◽  
Product Outcome

Abstract Background Two pneumococcal vaccines are currently recommended for use in U.S. adults: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Recommendations for adult PCV13 use were supported by a large randomized-controlled trial (RCT) demonstrating PCV13 efficacy against pneumococcal pneumonia (PnPn) and vaccine-type (VT) PnPn in older adults. New pneumococcal conjugate vaccines are expected to be licensed for adults in late 2021 and recommendations for use among adults will be reviewed and revised, as needed. We conducted a systematic review to summarize evidence on the vaccine efficacy and effectiveness (VE) of PPSV23 and PCV13 against PnPn among adults. Methods We conducted a search of literature published from 1998 to February 2021 on PCV13 and PPSV23 VE studies using eight reference databases. Studies targeting adults with immunocompromising conditions were excluded. VE results with 95% confidence intervals (CI) were abstracted and stratified by vaccine product, outcome evaluated (PnPn and VT PnPn), study design, and effect measure. When applicable, random effects models were used to estimate pooled VE and I-squared statistic was reported to assess heterogeneity. Results Of 3,422 screened studies, we included 15 studies: three on PCV13 and 12 on PPSV23 (Table 1). In addition to the RCT, we identified two observational studies for PCV13 (Table 1); however, pooled VE of the observational studies was not estimated due to differences in methods for reporting results. Pooled PPSV23 VE against PnPn from two RCTs was 63% (95% CI: 31, 80 I2=0%). Pooled VE of PPSV23 against VT PnPn from three observational studies was 18% (95% CI: -35, 35 I2=38%). PPSV23 effectiveness against PnPn was limited with a pooled VE of 25% (95% CI: 7, 39 I2=78%) from nine observational studies. Conclusion Findings from observational studies supported PCV13 VE against VT PnPn reported in the RCT. Differences in the study design made the magnitude of PPSV23 effectiveness against PnPn and VT PnPn difficult to assess; however, findings from recent observational studies suggest PPSV23 provides limited protection against VT PnPn. Disclosures All Authors: No reported disclosures

scholarly journals Effects of Intake of Apples, Pears, or Their Products on Cardiometabolic Risk Factors and Clinical Outcomes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 3 (10) ◽  
Author(s):  
Bridget A Gayer ◽  
Esther E Avendano ◽  
Emily Edelson ◽  
Nanguneri Nirmala ◽  
Elizabeth J Johnson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Observational Studies ◽  
Cardiovascular Health ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Random Effects Models ◽  
Nonrandomized Trial ◽  
Commonwealth Agricultural Bureau

ABSTRACT Apples and pears contain nutrients that have been linked to cardiovascular health. We conducted a systematic review and meta-analysis to summarize related research. Medline, Cochrane Central, and Commonwealth Agricultural Bureau databases were searched for publications on apple or pear intake and cardiovascular disease (CVD)/ cardiometabolic disease (CMD). Studies in adults (healthy or at risk for CVD) that quantified apple or pear intake were included. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome. In total, 22 studies were eligible including 7 randomized controlled trial, 1 nonrandomized trial, and 14 prospective observational studies. In RCTs, apple intake significantly decreased BMI, but made no difference in body weight, serum lipids, blood glucose, or blood pressure. In observational studies, apple or pear intake significantly decreased risk of cerebrovascular disease, cardiovascular death, type 2 diabetes mellitus, and all-cause mortality. No association was reported for cerebral infarction or intracerebral hemorrhage. In conclusion, apple or pear intake significantly decreased BMI and risk for CVD outcomes.

scholarly journals Pregnancy-related complications and incidence of atrial fibrillation: a systematic review and meta-analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
T Al Bahhawi ◽  
A Aqeeli ◽  
S L Harrison ◽  
D A Lane ◽  
I Buchan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Cohort Studies ◽  
Observational Studies ◽  
Large Scale ◽  
Data Extraction ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Random Effects Models ◽  
Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background Pregnancy-related complications have been previously associated with incident cardiovascular disease. However, data are scarce on the association between pregnancy-related complications and incident atrial fibrillation (AF). This systematic review examines associations between pregnancy-related complications and incident AF. Methods A systematic search of the literature utilising MEDLINE and EMBASE (Ovid) was conducted from 1990 to 6 April 2020. Observational studies examining the association between pregnancy-related complications including hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, low birth weight, small-for-gestational-age and stillbirth, and incidence of AF were included. Screening and data extraction were conducted independently by two reviewers. Inverse-variance random-effects models were used to pool hazard ratios. Results: Six observational studies met the inclusion criteria one case-control study and five retrospective cohort studies, with four studies eligible for meta-analysis.  Sample sizes ranged from 1,839-1,303,365. Mean/median follow-up for the cohort studies ranged from 7-36 years. Most studies reported an increased risk of incident AF associated with pregnancy-related complications. The pooled summary statistic from four studies reflected a greater risk of incident AF for HDP (hazard ratio (HR) 1.47, 95% confidence intervals (CI) 1.18-1.84; I2 = 84%) and from three studies for pre-eclampsia (HR 1.71, 95% CI 1.41-2.06; I2 = 64%; Figure). Conclusions The results of this review suggest that pregnancy-related complications particularly pre-eclampsia appear to be associated with higher risk of incident AF. The small number of included studies and the significant heterogeneity in the pooled results suggest further large-scale prospective studies are required to confirm the association between pregnancy-related complications and AF. Abstract Figure.

scholarly journals Aspirin and fracture risk: a systematic review and exploratory meta-analysis of observational studies

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e026876 ◽  
Author(s):  
A L Barker ◽  
Sze-Ee Soh ◽  
Kerrie M Sanders ◽  
Julie Pasco ◽  
Sundeep Khosla ◽  
...  
Keyword(s):  
Systematic Review ◽  
Fracture Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Large Population ◽  
Mineral Density ◽  
Random Effects Models ◽  
Manual Search ◽  
Relative Risks ◽  
Hip Bmd

ObjectivesThis review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin.MethodsWe conducted a systematic review and exploratory meta-analysis of observational studies. Electronic searches of MEDLINE and Embase, and a manual search of bibliographies was undertaken for studies published to 28 March 2018. Studies were included if: participants were men or women aged ≥18 years; the exposure of interest was aspirin; and relative risks, ORs and 95% CIs for the risk of fracture or difference (percentage or absolute) in BMD (measured by dual energy X-ray absorptiometry) between aspirin users and non-users were presented. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists for observational studies. Pooled ORs for any fracture and standardised mean differences (SMDs) for BMD outcomes were calculated using random-effects models.ResultsTwelve studies met the inclusion criteria and were included in the meta-analysis. Aspirin use was associated with a 17% lower odds for any fracture (OR 0.83, 95% CI 0.70 to 0.99; I2=71%; six studies; n=511 390). Aspirin was associated with a higher total hip BMD for women (SMD 0.03, 95% CI −0.02 to 0.07; I2=0%; three studies; n=9686) and men (SMD 0.06, 95% CI −0.02 to 0.13, I2=0%; two studies; n=4137) although these associations were not significant. Similar results were observed for lumbar spine BMD in women (SMD 0.03, 95% CI −0.03 to 0.09; I2=34%; four studies; n=11 330) and men (SMD 0.08; 95% CI −0.01 to 0.18; one study; n=432).ConclusionsWhile the benefits of reduced fracture risk and higher BMD from aspirin use may be modest for individuals, if confirmed in prospective controlled trials, they may confer a large population benefit given the common use of aspirin in older people.

Systematic review of interventions to facilitate advance care planning (ACP) in cancer patients.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 21-21 ◽  
Author(s):  
Bryan Chan ◽  
Hao-Wen Sim ◽  
Camilla Zimmermann ◽  
Monika K. Krzyzanowska
Keyword(s):  
Systematic Review ◽  
Health Care Providers ◽  
Study Design ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Small Sample ◽  
Study Quality ◽  
Care Providers ◽  
Documentation System ◽  
Code Status

21 Background: ACP refers to the process of consideration, documentation and communication of preferences for future care. ACP is crucial for patients (pts) with advanced cancer as it can guide substitute decision makers (SDM) and health care providers (HCP) to align care with preferences, thus improving quality of end-of-life care. Methods: We performed a systematic review of MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane (Systematic Review and Clinical Trial) databases (1995 to 2015) to identify interventions that facilitate ACP for cancer pts (documentation or discussion of advance directives, SDM or code status). We extracted data on study design, setting, subject numbers, interventions and outcomes. Study quality was assessed using a modified Downs and Black checklist. Results: Of the 64,196 unique citations identified, 10 studies met inclusion criteria for testing interventions using a pre-post or controlled trial design (median sample size 134, range 48-9105). Interventions were categorized based on target audience: health system (n = 4), pts and caregivers (n = 3) or HCP (n = 3). Types of interventions included: introduction of ACP facilitators (n = 4), reminders or prompts (n = 2), and HCP training, videos, website or pt screening (n = 1 each). Heterogeneity in study design, outcome measures and small sample sizes limited study quality and precluded meta-analysis. Prompts such as medical record or email reminders were most consistently associated with improved ACP documentation. System changes incorporating the use of ACP facilitators also improved ACP documentation in 3 out of 4 studies. Interactive HCP training significantly improved confidence to initiate ACP discussions which has been identified as a barrier to timely ACP. Pilot trials showed no significant increase in ACP with educational videos/websites directed at pts. Passive HCP education and one-off reminders were also ineffective. Conclusions: The complexity of ACP is reflected in the multitude of interventions that have been evaluated but none are ready for wide-scale adoption. Further studies of interventions such as prompts and ACP facilitators are needed to inform the best approach to improve ACP uptake in cancer pts.

scholarly journals Relationship between Smoking and Acute Mountain Sickness: A Meta-Analysis of Observational Studies

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Cristina Masuet-Aumatell ◽  
Alba Sánchez-Mascuñano ◽  
Fernando Agüero Santangelo ◽  
Sergio Morchón Ramos ◽  
Josep Maria Ramon-Torrell
Keyword(s):  
Study Design ◽  
Observational Studies ◽  
Smoking Status ◽  
Meta Analysis ◽  
Acute Mountain Sickness ◽  
Significant Heterogeneity ◽  
Random Effects Models ◽  
Relative Risks ◽  
Mountain Sickness ◽  
The Relationship

Aims. Previous epidemiological investigations of the relationship between smoking and acute mountain sickness (AMS) risk yielded inconsistent findings. Therefore, a meta-analysis of observational studies was performed to determine whether smoking is related to the development of AMS. Methods. Searches were performed on PubMed, Scopus, Embase, and Web of Science for relevant studies that were published before November 2016 reporting smoking prevalence and AMS. Two evaluators independently selected studies, extracted data, and assessed study quality. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were obtained using random-effects models. Subgroup analyses were performed according to the type of participant, altitude, and study design. Results. A total of 11 observational studies involving 7,106 participants, 2,408 of which had AMS, were eligible for inclusion in this meta-analysis. The summary RR for AMS comparing smokers to nonsmokers was 1.02 (95% CI: 0.83 to 1.26). Specific analyses for altitude, type of participant, and study design yielded similar results. There was significant heterogeneity for all studies (Q=37.43; P<0.001; I2=73%, 95% CI: 51% to 85%). No publication bias was observed (Egger’s test: P=0.548, Begg’s test: P=0.418). Conclusions. The meta-analysis indicates that no difference was found in AMS risk with regard to smoking status.

Nut Intake and Risk of Cancer and its Mortality: a Study Protocol for a Systematic Review and Dose-Response Meta-analysis of Observational Studies

2020 ◽  
Author(s):  
Sina Naghshi ◽  
Omid Sadeghi ◽  
Mohammad Naemi ◽  
Mehrasa Moezrad
Keyword(s):  
Systematic Review ◽  
Cancer Risk ◽  
Study Protocol ◽  
Dose Response ◽  
Observational Studies ◽  
Meta Analysis ◽  
Target Population ◽  
Random Effects Models ◽  
Risk Of Cancer ◽  
Nut Intake

Background: This study protocol outlines the planned, systematic review and dose-response meta-analysis of nuts intake with cancer risk and its mortality. Methods: This meta-analysis will be done based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). A systematic literature search will be conducted using online databases, including PubMed/Medline, ISI Web of Science, and Scopus with no limitation in language or time of publication to identify observational studies investigating the association of nuts intake with cancer risk and its mortality. The target population will be adults (≥18 years of age). Random-effects models will be used to calculate pooled effect sizes (ESs) for the risk of cancer and its mortality based on the comparison between the highest and lowest categories of nut intake and to incorporate variation between studies. Linear and non-linear dose-response analyses will be done to evaluate the dose-response associations between nut intake and risk of cancer and its mortality. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias or quality of included studies. Conclusion: The findings of this systematic review and dose-response meta-analysis will summarize all available evidence on the association between nut intake and risk of cancer and its mortality.

scholarly journals 21. Systematic Review and Meta-Analysis of Pneumococcal Vaccine Effectiveness against Invasive Pneumococcal Disease among Adults

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S134-S135
Author(s):  
Jennifer Loo Farrar ◽  
Miwako Kobayashi ◽  
Lana Childs ◽  
Tamara Pilishvili
Keyword(s):  
Systematic Review ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Vaccine ◽  
Observational Studies ◽  
Pneumococcal Disease ◽  
English Literature ◽  
Meta Analysis ◽  
Vaccine Effectiveness ◽  
Vaccine Type ◽  
Effectiveness Studies

Abstract Background Two new pneumococcal conjugate vaccines (PCVs), PCV15 and PCV20, are anticipated to be licensed for use in U.S. adults in 2021. To help inform the U.S. Advisory Committee on Immunization Practices’ discussions on pneumococcal vaccine use among adults, we conducted a systematic review and meta-analysis. We specifically looked at efficacy or effectiveness of PCV13 and pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) in adults. Methods We conducted a search of English literature published from 1998 – February 2021 on PCV13 and PPSV23 efficacy or effectiveness studies using eight major databases. Studies targeting adults with immunocompromising conditions were excluded. Title and abstract screening of identified studies and data abstraction were performed by two reviewers. Results were stratified by vaccine product, outcome evaluated (vaccine type (VT) or all IPD), study design, and effect measure. Random effects models were used to pool estimates by stratum. Results Of 3,422 citations reviewed, we identified 26 IPD studies; 4 on PCV13, 22 on PPSV23, 18 with all IPD, and 17 with VT-IPD (Table) as an outcome. Only one randomized-controlled trial (RCT) was identified for PCV13 with an efficacy of 52% (95% CI: 22%, 77%) against all IPD and 75% (95% CI: 41%, 91%) against VT-IPD. A pooled vaccine effectiveness (VE) estimate from three observational studies evaluating PCV13 was 56% (95% CI: 32%, 71%; I2 =12.8) against VT-IPD. Two RCTs evaluating PPSV23 reported efficacies against all IPD ranging between 79-86%; an additional RCT reported no IPD cases during RCT. Vaccine effectiveness estimates from 14 observational studies evaluating PPSV23 ranged between 29-76% against all IPD. Pooled VE estimates from 12 observational studies showed PPSV23 effectiveness against VT-IPD was 38% (95% CI: 28% to 46%; I2 =40.8). Table. Efficacy and effectiveness studies against vaccine-type invasive pneumococcal disease Conclusion Evidence suggests both pneumococcal vaccines are effective against VT-IPD in adults. Given that PCV15 and PCV20 are expected to be licensed based on immunogenicity data and no clinical efficacy data are available for these new vaccines, the findings from this review will help inform policy discussions on use of the new PCVs among adults. Disclosures All Authors: No reported disclosures

scholarly journals Smoking May Reduce the Effectiveness of Anti-TNF Therapies to Induce Clinical Response and Remission in Crohn’s Disease: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Sangmin Lee ◽  
M Ellen Kuenzig ◽  
Amanda Ricciuto ◽  
Ziyu Zhang ◽  
Hang Hock Shim ◽  
...  
Keyword(s):  
Systematic Review ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Observational Studies ◽  
Smoking Status ◽  
Meta Analysis ◽  
Short Term ◽  
Random Effects Models ◽  
Randomised Controlled

Abstract Background and Aims Cigarette smoking worsens prognosis of Crohn’s disease [CD]. We conducted a systematic review and meta-analysis to examine the association between smoking and induction of clinical response or remission with anti-tumour necrosis factor [TNF] therapy. Methods MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL [June 2019] were searched for studies reporting the effect of smoking on short-term clinical response and remission to anti-TNF therapy [≤16 weeks following the first treatment] in patients with CD. Risk ratios [RR] with 95% confidence intervals [CI] were calculated using random-effects models. Results Eighteen observational studies and three randomised controlled trials [RCT] were included. Current smokers and non-smokers [never or former] had similar rates of clinical response [observational studies RR: 0.96; 95% CI: 0.88, 1.05; RCTs RR: 1.09; 95% CI: 0.84, 1.41]. When restricted to studies clearly defining the smoking exposure, smokers treated with anti-TNF were less likely to achieve clinical response than non-smokers [smokers defined as having ≥5 cigarettes/day for ≥6 months RR: 0.63; 95% CI: 0.48, 0.83; lifetime never smokers vs ever smokers excluding former smokers RR: 0.81; 95% CI: 0.71, 0.93]. Current smokers were also less likely to achieve clinical remission in observational studies [RR: 0.75; 95% CI: 0.57, 0.98], though this association was not seen in RCTs [RR: 1.04; 95% CI: 0.89, 1.21]. Conclusions Smoking is significantly associated with a reduction in the ability of infliximab or adalimumab to induce short-term clinical response and remission when pooling studies where smoking status was clearly defined. When patients with CD are treated with highly effective therapy, including anti-TNF agents, concurrent smoking cessation may improve clinical outcomes.

scholarly journals Pneumococcal pneumonia and carriage in Africa before and after introduction of pneumococcal conjugate vaccines, 2000–2019: protocol for systematic review

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e030981 ◽  
Author(s):  
Newton L. Kalata ◽  
Tinashe K. Nyazika ◽  
Todd D. Swarthout ◽  
Dean Everett ◽  
Neil French ◽  
...  
Keyword(s):  
Systematic Review ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Pneumococcal Pneumonia ◽  
Meta Analysis ◽  
Published Data ◽  
National Immunisation Programme ◽  
Pneumococcal Carriage ◽  
Vaccine Type ◽  
The Impact

IntroductionAfrica harbours a high burden of pneumococcal disease, with associated high mortality rates. Despite 34 countries introducing the pneumococcal conjugate vaccine, which reduces the risk of pneumococcal carriage (a prerequisite for disease) of some of the most pathogenic pneumococcal serotypes, it remains uncertain whether they will achieve the sustained direct or indirect protection necessary to reduce pneumococcal carriage to levels sufficient to interrupt transmission and disease. We will therefore summarise the available data on the impact of the pneumococcal conjugate vaccine in reducing vaccine serotype carriage and pneumococcal pneumonia in Africa between 2000 and 2019.Methods and analysisUsing a predetermined search strategy, we will conduct a comprehensive search of PubMed, MEDLINE database, the Excerpta Medica Database, the ISI Web of Science (Science Citation Index), Scopus and the African Index Medicus to identify published studies reporting the prevalence of Streptococcus pneumoniae carriage (vaccine type and non-vaccine type), incidence rates of pneumococcal pneumonia and mortality among children, adults and HIV-infected (all-ages) pre-pneumococcal conjugate vaccine (PCV) and post-PCV introduction (published between 1st January 2000 and 31st December 2019) in African countries that have introduced PCVs (PCV7/PCV10/PCV13) in their routine national immunisation programme. The studies retained and data extracted will be assessed for bias using prevalidated tools and checklists. Heterogeneity across studies will be assessed using the χ2 test on Cochrane Q statistic. A random effect meta-analysis will be used to estimate the overall prevalence of pneumococcal carriage and incidence of pneumococcal pneumonia across studies with similar characteristics. Results will be reported in compliance with the Meta-Analysis Of Observational Studies in Epidemiology guidelines. The protocol has been prepared in accordance to the 2015 guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Ethics and disseminationThis systematic review will not require ethical approval as we will be using already published data. The final manuscript will be submitted for publication in a peer-reviewed journal and presented at conferences.PROSPERO registration numberCRD42019130976.

scholarly journals Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260844
Author(s):  
Karel H. van der Pol ◽  
Kimberley E. Wever ◽  
Mariette Verbakel ◽  
Frank L. J. Visseren ◽  
Jan H. Cornel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Cardiovascular Mortality ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Serum Urate ◽  
Cochrane Library ◽  
Cardiovascular Morbidity And Mortality

Aims To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients. Methods and results Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT’s a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT’s and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l). Conclusions Data from RCT’s and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia. Systematic review registration PROSPERO registration CRD42018089744

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