Assessing the potential for precision medicine in body weight reduction with regard to type 2 diabetes mellitus therapies: A meta-regression analysis of 120 randomized controlled trials.

AIMS: To assess the potential for precision medicine in type 2 diabetes by quantifying the variability of body weight as response to pharmacological treatment and to identify predictors which could explain this variability. METHODS: We used randomized clinical trials (RCTs) comparing glucose-lowering drugs (including but not limited to sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and thiazolidinediones) to placebo from four recent systematic reviews. RCTs reporting on body weight after treatment to allow for calculation of its logarithmic standard deviation (log[SD], i.e., treatment response heterogeneity) in verum (i.e., treatment) and placebo groups were included. Meta-regression analyses were performed with respect to variability of body weight after treatment and potential predictors. RESULTS: A total of 120 RCTs with a total of 43 663 participants were analysed. A slightly larger treatment response heterogeneity was shown in the verum groups, with a median log(SD) of 2.83 compared to 2.79 from placebo. After full adjustment in the meta-regression model, the difference in body weight log(SD) was -0.026 (95% confidence interval -0.044; 0.008), with greater variability in the placebo groups. Scatterplots did not show any slope divergence (i.e., interaction) between clinical predictors and the respective treatment (verum or placebo). CONCLUSIONS: We found no major treatment response heterogeneity in RCTs of glucose-lowering drugs for body weight reduction in type 2 diabetes. The precision medicine approach may thus be of limited value in this setting.

Immature cell fractions after cessation of chronic P2Y12-inhibition in patients with coronary artery diseases.

Changes in circulating cell populations may promote ischemic events that occur soon after discontinuation of P2Y12-inhibition. The aim of the study was to track the course of thrombopoietic and erythropoietic cells in patients with coronary artery diseases (CAD) after planned and physician-driven cessation of chronic P2Y12-inhibition (clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID). Cell fractions were determined in 62 patients at baseline (the last day of P2Y12-inhibitor intake), on day-10, day-30, and day-180 thereafter. Immature platelet fraction (IPF), immature reticulocyte fraction (IRF), reticulocyte hemoglobin content (Ret-Hb) and red blood cell count (RBC) significantly increased from baseline to day-180 (IPF: p = .003; IRF: p = .013; Ret-Hb: p < .001; RBC: p = .044). Platelet count, leucocyte count and immature granulocyte fraction did not change over time (p = .561, p = .869, and p = .161, respectively). Fibrinogen levels significantly declined over time (p = .011), thrombopoietin levels increased in a non-significant manner (p = .379). We did not observe any significant interaction with choice of P2Y12-inhibitor, therefore suggesting a drug class-effect. Our data shows, that discontinuation of dual antiplatelet therapy is associated with raised thrombopoietic and erythropoietic activity in the bone marrow, without significant upregulation of thrombopoietin. This provides further evidence for a direct stimulation of precursor cells by P2Y12-inhibitors.

Gender-based differences of copeptin alone or combined with troponin for early rule-out of non-ST-elevation myocardial infarction.

BACKGROUND: Little is known about the role of gender in the dual biomarker strategy using copeptin and troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate gender-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission. METHODS: Biomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by gender. RESULTS: Overall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36 pmol/L vs. 4.8 pmol/L; P < .001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8-100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV = 98.7%, CI: 97.5-99.8; and women, NPV = 98.7%, CI: 97.5-100). Multivariate logistic regression showed positive association of male gender with copeptin elevation (OR = 2.37; CI: 1.61-3.49; P < .001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR = 0.98, 95% CI: 0.96-0.99), while positive predictors were current MI (OR = 2.16, 95% CI: 1.19-3.91), chronic renal insufficiency (OR = 3.58, 95% CI: 1.33-9.62), and atrial fibrillation (OR = 2.56, 95% CI: 1.23-5.32), respectively (all P < .05). In women, current MI (OR = 2.98, CI: 1.23-7.24), atrial fibrillation (OR = 2.90, CI: 1.26-6.70) and syncope-like events (OR = 7.56, CI: 2.26-25.30) were significant predictors of copeptin elevation. CONCLUSIONS: Men with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are gender-specific.

Course of platelet miRNAs after cessation of P2Y12 antagonists.

BACKGROUND: Circulating platelet micro-RNAs (miRNAs) may be used to monitor platelet function during dual antiplatelet therapy (DAPT). Aim of the study was to measure plasma levels of specific miRNAs (miRNA-223, -150, -21 and -126) after physician-driven cessation of chronic P2Y12 inhibition and to study differences in the expression levels of these miRNAs between the different oral P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor, respectively. DESIGN: Patients with coronary artery disease (CAD) on DAPT maintenance dose (including aspirin 100 mg OD, plus clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID) were prospectively enrolled before cessation of the P2Y12-inhibitor therapy. MiRNA-223, -150, -21 and -126 were determined at baseline (=last day of P2Y12-inhibitor intake) and 10, 30 and 180 days thereafter. RESULTS: Cessation of P2Y12-inhibitor therapy did not significantly change miRNA levels. However, in ticagrelor-treated patients, miRNA levels were significantly increased at baseline (miRNA-223 and -21), day 10 (miRNA-223, -150, -21, -126) and day 30 (miRNA-223, -150, -21, -126) as compared to prasugrel, and at day 10 (miRNA-150 and -21) and day 30 (miRNA-150) as compared to clopidogrel (all P < 0.05). At day 180, only miRNA-126 levels differed significantly with respect to the P2Y12 inhibitor used (P < 0.05). After adjustment for confounders, choice of P2Y12-inhibitor was the strongest predictor of miRNA levels (P < 0.001), while cessation of P2Y12-inhibitor therapy did not significantly impact miRNA levels. CONCLUSION: In patients with CAD, ticagrelor intake is associated with increased levels of platelet miRNAs as compared to clopidogrel and prasugrel. Platelet miRNAs are not useful to monitor platelet function after cessation of P2Y12 inhibitors.

Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis.

OBJECTIVE:: To review evidence on the efficacy of HPV vaccines in the prevention of non-cancer lesions (anogenital warts [AGW], recurrent laryngeal papillomatosis and oral papillomatosis). MATERIALS AND METHODS:: We conducted a systematic review of randomized trials. We performed random effect models and effects were reported as relative risks (RR) and their confidence intervals (95%CI) following both intention to treat (ITT) and per protocol (PP) analyses. RESULTS:: We included six studies (n=27 078). One study was rated as high risk of bias. One study could not be included in the meta-analysis because it provided combined results. We found that quadrivalent vaccine reduced the risk of AGW by 62% (RR: 0.38, 95%CI:0.32-0.45, I2:0%) in the ITT analysis and by 95% (RR: 0.05, 95%CI:0.01-0.25, I2:66%) in the PP analysis. Subgroup analyses of studies in women or with low-risk of bias provided similar results. CONCLUSION:: HPV quadrivalent vaccine is efficacious in preventing AGW in men and women.

Copeptin for the differentiation of type 1 versus type 2 myocardial infarction or myocardial injury.

BACKGROUND: The rapid and reliable differentiation of myocardial infarction (MI) due to atherothrombosis (T1MI) from MI due to supply-demand mismatch (T2MI) or acute myocardial injury is of major clinical relevance due to very different treatments, but still a major unmet clinical need. This study aimed to investigate whether copeptin, a stress hormone produced in the hypothalamus, helps to differentiate between T1MI versus T2MI or injury. METHODS: In a retrospective analysis, 1271 unselected consecutive patients presenting with symptoms suggestive of MI to the emergency department were evaluated. Patients diagnosed with ST-elevation MI were excluded. All patients with elevated cardiac troponin I (cTnI) concentration possibly indicating MI were classified into T1MI, T2MI, or acute myocardial injury using detailed clinical assessment and coronary imaging. Copeptin plasma concentration was measured in a blinded fashion. A multicenter diagnostic study with central adjudication of the final diagnosis served as external validation cohort (n = 1390). RESULTS: Among 1161 patients, 154 patients had increased cTnI concentration. Of these, 78 patients (51%) were classified as T1MI and 76 (49%) as T2MI or myocardial injury. Patients with T2MI or myocardial injury had significantly higher copeptin plasma concentration between patients versus T1MI (21,4 pmol/l versus 8,1 pmol/l, p = 0,001). A multivariable regression analysis revealed that higher concentrations of copeptin and C-reactive protein, higher heart rate at presentation and lower frequency of smoking remained significantly associated with T2MI and myocardial injury. Findings were largely confirmed in the external validation cohort. CONCLUSION: In patients without ST-segment elevation, copeptin concentration was higher in T2MI and myocardial Injury versus T1MI and may help in their differential diagnosis.

Impella in cardiogenic shock following acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Cardiogenic shock (CS) conveys a high mortality risk. A cardiac assist device may serve as bridge to patient recovery. We aimed to provide a pooled estimate on mortality and complications from studies evaluating the use of the left ventricular assist device Impella in CS following acute myocardial infarction. In addition, we evaluated whether mortality risk differed with device placement before or after percutaneous coronary intervention (PCI). METHODS: We searched Medline, Embase and Web of Science from 2005 until July 2019 for observational studies or clinical trials on this specific patient group. Studies were required to report on 30-day all-cause mortality and device-related complications. We calculated pooled proportions with 95% confidence intervals (CI) using random effects models and the inverse variance method. RESULTS: Overall, 671 patients from 11 studies (2 randomized and 9 observational) were included. Pooled proportions showed a 30-day mortality of 54.6% (95% CI 47.3-61.8; P = 0.22; I2 = 65.8%). Among complications, major bleeding was found in 19.9% (95% CI 14.2-27.3; P < 0.05; I2 = 69.1%), hemolysis in 10.5% (95% CI 7.2-15.0; P < 0.05; I2 = 52.1%), limb ischemia in 5.0% (95% CI 2.6-9.5; P < 0.05; I2 = 48.3%) and stroke in 3.8% of patients (95% CI 2.4-5.9; P < 0.05; I2 = 0%). Sensitivity analysis demonstrated a statistically significant risk reduction in 30-day mortality when Impella was implanted prior to PCI as compared to after PCI, risk ratio (RR): 0.71, CI 0.58-0.86, P = 0.001, I2 = 0%. CONCLUSION: Pooled estimates of Impella use in myocardial infarction with CS revealed a high 30-day mortality; however, as compared to post-PCI, Impella initiation prior to PCI was associated with a survival benefit.

Remote ischaemic conditioning for myocardial infarction or elective PCI: systematic review and meta-analyses of randomised trials.

BACKGROUND: The efficacy of remote ischaemic conditioning in clinical trials of ST-segment elevation myocardial infarction (STEMI) or elective percutaneous coronary intervention is controversial. We aimed to systematically review and meta-analyse whether remote ischaemic conditioning reduces myocardial damage in those patients. METHODS: We searched PubMed, Embase and Web of Science from inception until December 2017 for randomised clinical trials evaluating remote ischaemic conditioning versus a control group. Two independent reviewers extracted data of 23 trials (2118 patients with STEMI; 2048 patients undergoing elective percutaneous coronary intervention) which were meta-analysed using random-effects models. RESULTS: Remote ischaemic conditioning reduced infarct size in STEMI patients when assessed by imaging (mean difference of infarct size as percentage of left ventricle -2.43, 95% confidence interval (CI) -4.37 to -0.48; P=0.01; I2=44%; n=925) or biomarkers related to myocardial injury (peak values of cardiac biomarker release reported as standardised mean difference -0.19, 95% CI -0.37 to -0.02; P=0.03; I2=58%; n=1483) and increased myocardial salvage index (mean difference 0.07, 95% CI 0.01 to 0.13; P=0.02; I2=49%; n= 636). Left ventricular ejection fraction was increased when assessed during the first days after STEMI (mean difference 1.53, 95% CI 0.23 to 2.83; P=0.02; I2=28%; n=1192). Remote ischaemic conditioning had no influence on biomarker values after elective percutaneous coronary intervention (standardised mean difference 0.06, 95% CI -0.17 to 0.30; P=0.59). CONCLUSIONS: Despite a statistically significant reduction of myocardial damage in STEMI patients, the magnitude of the reduction was small and a significant impact on clinical events is unlikely. With respect to elective percutaneous coronary intervention, remote ischaemic conditioning had no influence on myocardial injury and its use is not supported by our analysis.

MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease.

Microribonucleic acids (miRs) are small, noncoding ribonucleic acids (RNAs), which play an important role in the regulation of platelet function and activity. Several studies proposed a mechanistic role of platelet-related miRs in the pathophysiology of coronary artery disease (CAD) and atherothrombosis. Circulating, platelet-related miRs have been proposed as diagnostic, prognostic, as well as treatment response biomarkers in CAD and acute coronary syndrome (ACS). In this review, we summarize recent studies on the role of platelet-related miRs in the regulation of platelet function and activity. Furthermore, we review the studies investigating the role of platelet-related miRs as biomarkers in patients with CAD and ACS.

Variations on classification of main types of myocardial infarction: a systematic review and outcome meta-analysis.

OBJECTIVE: Classifying myocardial infarction into type 1 (T1MI) or type 2 (T2MI) remains a challenge in clinical practice. We aimed to identify factors contributing to variation in the classifications of MI into type 1 or type 2. In addition, pooled analyses of long-term mortality and reinfarction outcomes were performed. METHODS: We searched Medline, Embase and Web of Science through January 2018 for observational studies or clinical trials classifying patients as either T1MI or T2MI. Studies with baseline characteristics allowing a comparison between both groups were included. Inverse variance random-effects models were used to pool risk ratios (RR). RESULTS: Overall, 93,194 patients from 20 included observational studies were classified as T1MI and 9291 as T2MI; corresponding to 87.9% and 8.8% of all patients diagnosed with MI. Inclusion of ST-elevation MI patients was inconsistent among studies. Coronary angiography was performed in 77.7% and 31.5% of all patients with T1MI and T2MI, respectively. From a subgroup of 11 studies, percutaneous coronary intervention was performed in 79.2% of all patients classified as T1MI (range 44.2-93.0%) and 40.2% of all T2MI patients (range 0-87.5%). A meta-analysis of 6 studies (44,366 in total) on 2-year mortality showed worse outcome among T2MI patients (RR: 1.52, CI 1.07-2.17, P = 0.02; I2 = 92%). Risk of reinfarction at 1.6 years was higher among T2MI patients (RR: 1.68, CI 1.22-2.31, P = 0.001; I2 = 9%). CONCLUSIONS: Classification of T1MI and T2MI varies widely among studies. A standardized approach with clear definitions is needed to avoid misclassification and ensure appropriate patient management.

Prognostic impact of familial hypercholesterolemia on long-term outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Patients with familial hypercholesterolemia (FH) are at increased risk for premature and subsequent cardiovascular disease. Data on long-term major adverse cardiovascular events (MACE) in patients with FH after percutaneous coronary intervention (PCI) in the era of high-intensity statins are scarce. OBJECTIVE: We assessed the prognostic impact of clinically diagnosed FH on long-term MACE, a composite of all-cause death, myocardial infarction, and ischemic stroke in patients admitted for stable coronary artery disease (SCAD) or acute coronary syndromes (ACSs) undergoing PCI. METHODS: FH was diagnosed according to the Dutch Lipid Clinic Network diagnosis criteria: "Unlikely FH" diagnosis was defined as 0 to 2 points, "possible FH" as 3 to 5 points, and "probable/definite FH" diagnosis as 6 or higher. RESULTS: From a total of 1550 eligible patients (47.4% were admitted for SCAD and 52.6% for ACS), 77 (5.0%) were classified as probable/definite FH, 332 (21.4%) as possible FH, and 1141 (73.6%) as unlikely FH. Mean follow-up was 6.0 ± 2.4 years. After adjustment for possible confounders, patients classified with probable or definite FH (hazard ratio [HR] 1.922 [95% confidence interval (CI) 1.220-2.999]; P = .004), but not patients with possible FH (HR 1.105 [95% CI 0.843-1.447]; P = .470) faced a significant, approximately 2-fold increased risk of MACE compared with patients with unlikely FH. CONCLUSION: After adjustment for confounders, patients with probable or definite FH faced an approximate 2-fold increased risk for long-term MACE compared with patients without FH despite the widespread use of high-intensity statins. The new option of proprotein convertase subtilisin/kexin type 9 gene inhibitors in addition to other current optimal lipid-lowering strategies might help to further improve clinical outcome in patients with probable/definite FH.

Sex steroids, sex hormone-binding globulin and levels of N-terminal pro-brain natriuretic peptide in postmenopausal women.

BACKGROUND: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has a well-documented prognostic value for cardiovascular disease and sex-hormones are suggested to modulate NT-proBNP levels. OBJECTIVE: To examine whether endogenous sex-hormones and sex hormone-binding globulin (SHBG) are associated with NT-proBNP levels in postmenopausal women free of clinical cardiovascular diseases. METHODS: Total estradiol (E2), total testosterone (TT), androstenedione (AD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and NT-proBNP were assessed in 4112 postmenopausal women free of cardiovascular diseases from the prospective population-based Rotterdam Study. Free androgen index (FAI) was calculated as ratio of TT to SHBG concentration. TT, AD, DHEA(S), SHBG, FAI and NT-proBNP were natural log transformed. Regression coefficients and 95% Confidence Intervals (CI) were calculated using multivariable linear regression models adjusting for confounders. RESULTS: In models adjusted for multiple confounders (age, reproductive, life style and cardiovascular risk factors) higher SHBG (per 1 SD increase, ß = 0.15, 95% CI = 0.12, 0.18), and lower levels of TT (per 1 SD increase, ß = -0.05, 95%CI = -0.08, -0.02), FAI (per 1 SD increase, ß = -0.13, 95%CI = -0.15, -0.09), DHEAS (per 1 SD increase, ß = -0.06, 95% CI = -0.09, -0.04) and DHEA (per 1 SD increase, ß = -0.06, 95%CI = -0.09, -0.04) were associated with higher levels of NT-proBNP. However, no consistent association was found between E2 and AD and NT-proBNP levels. Additionally, stratification by BMI did not affect any of observed associations. CONCLUSION: Our findings support the hypothesis that higher androgens might be associated with lower natriuretic peptide levels in postmenopausal women.

Monocyte subsets in myocardial infarction: A review.

BACKGROUND: Monocytes form an important part of the human innate immune system by taking part in inflammatory reactions. With time, monocytes have gained interest in the role they may play during the event of myocardial infarction (MI). The current paradigm suggests that monocytes consist of three subdivisions which differ in phenotypic and dynamic patterns after an MI. In the inflammation that ensues, the different subsets have been shown to have an impact on reparative processes and patient recovery. METHODS & RESULTS: We searched Medline and Embase until April 5, 2016, for observational studies or clinical trials regarding monocyte functions and dynamics in MI. Apart from studies in humans, extensive work has been done in mice in an effort to understand the complex nature of monocyte dynamics. Animal models might add useful information on mapping these processes. CONCLUSION: The question still remains whether animal data can, to a certain degree, be extrapolated to monocyte functions during human MI. This review aims to summarize current available evidence on both mice and men with particular focus on the understanding of monocyte subsets dynamics and effects in human MI.

Copeptin for the early rule-out of non-ST-elevation myocardial infarction.

Copeptin, a neuropeptide of unknown pathophysiological function that is stoichiometrically secreted with the antidiuretic hormone, is a non-specific marker of endogenous stress which has recently gained interest for its use within a dual-marker strategy in combination with cardiac troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI) in emergency department patients with suspected MI. Based on methodologically strong and consistent evidence from large diagnostic studies and even one randomized intervention study, current European Society of Cardiology Guidelines recommend copeptin and the dual-marker strategy for the early rule-out of MI when high-sensitivity cardiac troponin (hs-cTn) assays are not available. When used with conventional cTn assays, the incremental value of copeptin is large. When used with hs-cTn, the incremental value is very small and does not justify routine clinical use. This review aims to describe the structure, function, and release mechanism of copeptin; as well as to provide an explanation on why this biomarker should be used in the rule-out, and not in the rule-in, of NSTEMI.

MicroRNAs as circulating biomarkers in acute coronary syndromes: A review.

Coronary artery disease (CAD) and its complications remain the most common cause of death worldwide. Cardiac troponins (cTn) are standard biomarkers used today for diagnosis and risk stratification of myocardial infarction (MI). Increasing efforts are made to develop additional, new biomarkers for more effective and safe rule-in and rule-out of MI patients at the emergency department. During the past decade, microRNAs (miRNAs) have emerged as new, potential diagnostic biomarkers in several diseases, including MI. In this review, we aimed to summarize some of the prominent studies in the field, and discuss the potential value of miRNAs in the diagnosis of MI.

The functions of estrogen receptor beta in the female brain: A systematic review.

Females have unique and additional risk factors for neurological disorders. Among classical estrogen receptors, estrogen receptor beta (ERß) has been suggested as a therapeutic target. However, little is known about the role of ERß in the female brain. Six electronic databases were searched for articles evaluating the role of ERß in the female brain and the influence of age and menopause on ERß function. After screening 3186 titles and abstracts, 49 articles were included in the review, all of which were animal studies. Of these, 19 focused on cellular signaling, 7 on neuroendocrine pathways, 8 on neurological disorders, 4 on neuroprotection and 19 on psychological and psychiatric outcomes (6 studies evaluated two or more outcomes). Our findings showed that ERß phosphorylated and activated intracellular second messenger proteins and regulated protein expression of genes involved in neurological functions. It also promoted neurogenesis, modulated the neuroendocrine regulation of stress response, conferred neuroprotection against ischemia and inflammation, and reduced anxiety- and depression-like behaviors. Targeting ERß may constitute a novel treatment for menopausal symptoms, including anxiety, depression, and neurological diseases. However, to establish potential therapeutic and preventive strategies targeting ERß, future studies should be conducted in humans to further our understanding of the importance of ERß in women's mental and cognitive health.

Estrogen receptor ß actions in the female cardiovascular system: A systematic review of animal and human studies.

Five medical databases were searched for studies that assessed the role of ERß in the female cardiovascular system and the influence of age and menopause on ERß functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERß signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERß signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERß may be vessel specific and may differ by age and menopause status. ERß seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERß-ligands might contribute to cardiovascular disease prevention.

Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis / Eficacia de la vacuna contra el virus del papiloma humano en la prevención de verrugas anogenitales: revisión sistemática y metanálisis

Abstract: Objective: To review evidence on the efficacy of HPV vaccines in the prevention of non-cancer lesions (anogenital warts [AGW], recurrent laryngeal papillomatosis and oral papillomatosis). Materials and methods: We conducted a systematic review of randomized trials. We performed random effect models and effects were reported as relative risks (RR) and their confidence intervals (95%CI) following both intention to treat (ITT) and per protocol (PP) analyses. Results: We included six studies (n=27 078). One study was rated as high risk of bias. One study could not be included in the meta-analysis because it provided combined results. We found that quadrivalent vaccine reduced the risk of AGW by 62% (RR: 0.38, 95%CI:0.32-0.45, I2:0%) in the ITT analysis and by 95% (RR: 0.05, 95%CI:0.01-0.25, I2:66%) in the PP analysis. Subgroup analyses of studies in women or with low-risk of bias provided similar results. Conclusion: HPV quadrivalent vaccine is efficacious in preventing AGW in men and women.

Resumen: Objetivo: Revisar la evidencia sobre la eficacia de las vacunas contra el virus del papiloma humano en la prevención de lesiones no oncológicas (verrugas anogenitales [VAG], papilomatosis recurrente respiratoria y papilomatosis oral). Material y métodos: Realizamos una revisión sistemática de ensayos clínicos aleatorizados. Empleamos modelos de efectos aleatorios, calculando riesgos relativos (RR) y sus intervalos de confianza al 95% (IC95%), utilizando el análisis por intención a tratar (ITT) y por protocolo (PP). Resultados: Seleccionamos seis estudios (n=27 078). Un estudio tuvo alto riesgo de sesgo y otro no fue incluido en el metanálisis. La vacuna cuadrivalente reduce el riesgo de VAG en 62% (RR: 0,38; IC95%:0,32-0,45; I2:0%) en el análisis ITT y en 95% (RR: 0,05; IC95%:0,01-0,25; I2:66%) en el análisis PP. Los análisis de subgrupos (mujeres y estudios con bajo riesgo de sesgo) proporcionaron resultados similares. Conclusión. La vacuna cuadrivalente es eficaz en la prevención de VAG en hombres y mujeres.