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The Lancet. Haematology Feb 2017Statins have been suggested to have a protective effect on venous thromboembolism (which includes deep vein thrombosis and pulmonary embolism), but the evidence is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins have been suggested to have a protective effect on venous thromboembolism (which includes deep vein thrombosis and pulmonary embolism), but the evidence is uncertain. We sought to evaluate the extent to which statins are associated with first venous thromboembolism events.
METHODS
We did a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs). Relevant studies that reported associations between statins and first venous thromboembolism outcomes were identified from MEDLINE, Embase, Web of Science, Cochrane Library, and a manual search of bibliographies for studies published up until July 18, 2016, and from email correspondence with investigators. Observational cohorts that assessed the association of statin use with venous thromboembolism, deep vein thrombosis, or pulmonary embolism in adults were included, as were intervention studies that assessed the effects of statin therapy compared with a placebo or no treatment and collected data on venous thromboembolism, deep vein thrombosis, or pulmonary embolism outcomes. Studies that compared statins with another statin or lipid-lowering agent were excluded. Study specific relative risks (RRs) were aggregated using random-effects models and were grouped by study-level characteristics. The review has been registered with PROSPERO, number CRD42016035622.
FINDINGS
36 eligible studies (13 cohort studies comprising 3 148 259 participants and 23 RCTs of statins vs placebo or no treatment comprising 118 464 participants) were included. In observational studies, the pooled RR for venous thromboembolism was 0·75 (95% CI 0·65-0·87; p<0·0001) when statin use was compared with no statin use. This association remained consistent when grouped by various study-level characteristics. In RCTs, the RR for venous thromboembolism was 0·85 (0·73-0·99; p=0·038) when statin therapy was compared with placebo or no treatment. Subgroup analyses suggested significant differences in the effect of statins by type of statin, with rosuvastatin having the lowest risk on venous thromboembolism compared with other statins 0·57 (0·42-0·75; p=0·015). There was no evidence of an effect of statin use on pulmonary embolism. Statin use was associated with a significant reduction in risk of the specific endpoint of deep vein thrombosis compared with no statin use (RR 0·77, 95% CI 0·69-0·86; p<0·0001).
INTERPRETATION
Available evidence from observational and intervention studies suggest a beneficial effect of statin use on venous thromboembolism. In intervention studies, therapy with rosuvastatin significantly reduced venous thromboembolism compared with other statins. Further evidence is however needed to validate these findings.
FUNDING
None.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Primary Prevention; Venous Thromboembolism
PubMed: 28089655
DOI: 10.1016/S2352-3026(16)30184-3 -
Atencion Primaria 2019To assess the effectiveness of the interventions to prevent a pregnancy in adolescence.
OBJECTIVE
To assess the effectiveness of the interventions to prevent a pregnancy in adolescence.
DESIGN
Systematic review.
DATA SOURCES
The following databases were consulted: PubMed, CINAHL, Scopus, Cuiden Plus, LILACS, and IME, in order to identify interventions aimed at preventing a pregnancy in adolescence.
STUDY SELECTION
A total of 24 primary investigations, in which an educational program to prevent a pregnancy in the adolescence was evaluated, were selected. The quality of the selected studies was assessed according to the CASPe scale.
RESULTS
Educational programs for the modification of the teenage pregnancy rate show inconclusive results, as there are 2 studies that find a reduction, and 2 that find that there are no significant changes. For secondary outcomes, it was found that educational programs are effective for increasing the knowledge level about sexuality and contraceptive methods and changing attitudes about the risk of a teenage pregnancy or the use of contraceptive methods. There are no statistically significant differences between the studies with a positive and negative outcome (P>.05) for any of the results analysed in this review.
CONCLUSION
There is no a single intervention modality that is the most effective for prevention of a teenage pregnancy. More research is needed with a longitudinal approach that assess not only intermediate results, but also a modification in the pregnancy rate.
Topics: Adolescent; Female; Health Education; Health Knowledge, Attitudes, Practice; Humans; Pregnancy; Pregnancy in Adolescence; Primary Prevention; Program Evaluation
PubMed: 29903543
DOI: 10.1016/j.aprim.2018.04.003 -
BMC Medicine Apr 2022Higher dietary fibre intakes are associated with a reduced risk of developing cardiovascular disease (CVD), and increasing intake has been shown to reduce blood pressure... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Higher dietary fibre intakes are associated with a reduced risk of developing cardiovascular disease (CVD), and increasing intake has been shown to reduce blood pressure and other cardiometabolic risk factors. The extent to which dietary fibre can further reduce risk for those with CVD and treated with cardioprotective drugs has not been clearly established. We have examined the evidence for dietary fibre as adjunct therapy in those with CVD or hypertension.
METHODS
Ovid MEDLINE, Embase, PubMed, and CENTRAL were searched to June 2021. Prospective observational studies reporting on fibre intakes and mortality in those with pre-existing CVD and controlled trials of increasing fibre intakes on cardiometabolic risk factors in those with CVD or hypertension were eligible. Outcomes were mortality (studies) and cardiometabolic risk factors (trials). Data synthesis was with random effects and dose response. Certainty of evidence was assessed using GRADE.
RESULTS
Three prospective studies including 7469 adults with CVD, and 12 trials of 878 adults with CVD or hypertension were identified. Moderate certainty evidence indicates reduced all-cause mortality (relative risk, RR0.75 (95% confidence interval, CI 0.58-0.97)) when comparing higher with lower fibre intakes. Low certainty evidence from trials of adults with cardiovascular disease indicates increasing fibre intakes reduced total (mean difference, MD - 0.42 mmol/L (95%CI - 0.78 to - 0.05) and low-density lipoprotein (LDL) cholesterol (MD - 0.47mmol/L (95%CI - 0.85 to - 0.10)). High certainty evidence from trials of adults with hypertension indicates increasing fibre intakes reduces systolic (MD 4.3 mmHg (95% CI 2.2 to 5.8)) and diastolic blood pressure (MD 3.1 mmHg (95% CI 1.7 to 4.4)). Moderate and low certainty evidence indicated improvements in fasting blood glucose (MD 0.48 mmol/L (- 0.91 to - 0.05)) and LDL cholesterol (MD 0.29 mmol/L (95% CI 0.17 to 0.40)). Benefits were observed irrespective of cardioprotective drug use.
CONCLUSIONS
These findings emphasise the likely benefits of promoting greater dietary fibre intakes for patients with CVD and hypertension. Further trials and cohort analyses in this area would increase confidence in these results.
Topics: Adult; Cardiovascular Diseases; Dietary Fiber; Humans; Hypertension; Observational Studies as Topic; Primary Prevention; Prospective Studies
PubMed: 35449060
DOI: 10.1186/s12916-022-02328-x -
Preventive Medicine Jun 2016Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) prevention programmes have been effective in urban residents, their effectiveness in non-urban... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) prevention programmes have been effective in urban residents, their effectiveness in non-urban settings, where cardio-metabolic risk is typically elevated, is unknown. We systematically reviewed the effectiveness of primary prevention programmes aimed at reducing risk factors for CVD/T2DM, including blood pressure, body mass index (BMI), blood lipid and glucose, diet, lifestyle, and knowledge in adults residing in non-urban areas.
METHODS
Twenty-five manuscripts, globally, from 1990 were selected for review (seven included in the meta-analyses) and classified according to: 1) study design (randomised controlled trial [RCT] or pre-/post-intervention); 2) intervention duration (short [<12months] or long term [≥12months]), and; 3) programme type (community-based programmes or non-community-based programmes).
RESULTS
Multiple strategies within interventions focusing on health behaviour change effectively reduced cardio-metabolic risk in non-urban individuals. Pre-/post-test design studies showed more favourable improvements generally, while RCTs showed greater improvements in physical activity and disease and risk knowledge. Short-term programmes were more effective than long-term programmes and in pre-/post-test designs reduced systolic blood pressure by 4.02mmHg (95% CI -6.25 to -1.79) versus 3.63mmHg (95% CI -7.34 to 0.08) in long-term programmes. Community-based programmes achieved good results for most risk factors except BMI and (glycated haemoglobin) HbA1c.
CONCLUSION
The setting for applying cardio-metabolic prevention programmes is important given its likelihood to influence programme efficacy. Further investigation is needed to elucidate the individual determinants of cardio-metabolic risk in non-urban populations and in contrast to urban populations.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Exercise; Health Behavior; Humans; Life Style; Primary Prevention; Risk Factors; Rural Population
PubMed: 26876624
DOI: 10.1016/j.ypmed.2016.02.011 -
BMC Endocrine Disorders Sep 2023Concerning ascending trend in the prevalence of chronic type II diabetes, prevention and the development of an effective approach after the recognition of at-risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Concerning ascending trend in the prevalence of chronic type II diabetes, prevention and the development of an effective approach after the recognition of at-risk individuals is crucial. This study aims to investigate comparing the influence of lifestyle modification and metformin interventions in the prevention of type II diabetes developments.
METHOD
The search was conducted using PubMed, Google Scholar, Scopus and Web of Science databases. The inclusion criteria include randomized controlled trials (RCT) which studied both lifestyle modification and metformin interventions in the population above 18 years old without a history of any type of diabetes. After excluding studies with intervention time of fewer than 6 months, a systematic review and meta-analysis were performed to evaluate relative risk (RR) with a confidence interval (CI) of 95% of type II diabetes development.
RESULTS
Data from 5 studies were included in the meta-analysis. The population also consists of individuals with a mean age of 50 years old with BMI and FBS of 35.5 and 104.7 mg/dl respectively. Participants range of prevention years was between 2-3 years with a mean of 2.8 years. Lifestyle modification decreases the probability of the incidence of type II diabetes by 25.3% (RR: 0.747, 95% CI, 0.6-0.92) compared to the metformin intervention (p-value = 0.007). Our results indicate that long-term lifestyle modifications can prevent diabetes type II and decrease diabetes mellitus incidence down to one-quarter in comparison to metformin.
CONCLUSION
Lifestyle modification can be more efficacious than metformin in diminishing the incidence of type II diabetes. Therefore, lifestyle modification can be a therapeutic strategy for controlling type II diabetes incidence, especially in high-risk individuals.
Topics: Humans; Middle Aged; Adolescent; Metformin; Diabetes Mellitus, Type 2; Behavior Therapy; Life Style; Primary Prevention
PubMed: 37723440
DOI: 10.1186/s12902-023-01445-9 -
Allergy May 2014Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults.
METHODS
Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized.
RESULTS
Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults.
CONCLUSIONS
There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved.
Topics: Adult; Breast Feeding; Child; Child, Preschool; Female; Food Hypersensitivity; Humans; Infant; Infant Formula; Infant, Newborn; Male; Pregnancy; Primary Prevention
PubMed: 24433563
DOI: 10.1111/all.12334 -
Phytomedicine : International Journal... Sep 2022To date, Nao-an capsules are the only Chinese patent medicine primarily prescribed for the primary prevention of stroke. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To date, Nao-an capsules are the only Chinese patent medicine primarily prescribed for the primary prevention of stroke.
PURPOSE
To evaluate the efficacy and safety of Nao-an capsules in the primary prevention of stroke in high-risk patients.
STUDY DESIGN
A systematic review and meta-analysis of randomized controlled trials.
METHODS
We searched 7 electronic databases and 2 registries from inception to January 13, 2022 for relevant randomized controlled trials. Two independent investigators selected trials, collected data, and judged the risk of bias. We performed a meta-analysis using the Review Manager software.
RESULTS
Nine randomized controlled trials involving 14 744 patients at high risk of stroke were included. Nao-an capsules reduced the risk of first stroke compared with no intervention (risk ratio [RR] = 0.49, 95 % confidence interval [CI] 0.29 to 0.82, p = 0.006) or aspirin (RR = 0.47, 95 % CI 0.25 to 0.91, p = 0.03; RR = 0.46, 95 % CI 0.22 to 0.99, p = 0.05), without increased bleeding risks. The certainty of evidence was evaluated as moderate to very low.
CONCLUSION
In addition to controlling specific risk factors, Nao-an capsules might provide additional preventive effects on first stroke with an acceptable safety profile for populations at high risk of stroke. However, as current evidence is too weak, a firm recommendation depends on further confirmation from more studies with more rigorous methodology.
Topics: Aspirin; Humans; Primary Prevention; Stroke
PubMed: 35772341
DOI: 10.1016/j.phymed.2022.154263 -
Drugs & Aging Aug 2015Statins have been shown to be beneficial in primary and secondary prevention settings; however, their role in the elderly remains a clinical conundrum, given that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins have been shown to be beneficial in primary and secondary prevention settings; however, their role in the elderly remains a clinical conundrum, given that age-related factors could alter the risk-benefit ratio of statin treatment. This study aimed to critically evaluate the efficacy and safety of statins for primary prevention of cardiovascular disease (CVD) in the elderly.
METHODS
We systematically reviewed randomized controlled trials comparing any statins with placebo or usual care for primary prevention of CVD in subjects aged ≥65 years. Relative risks (RRs) using a random effects model were calculated and sensitivity analyses were performed to assess the robustness of findings.
RESULTS
Eight studies (n = 25,952) were included in the meta-analysis. Statins significantly reduced the risks of composite major adverse cardiovascular events (RR 0.82, 95% CI 0.74-0.92), nonfatal myocardial infarction [MI] (0.75, 0.59-0.94) and total MI (0.74, 0.61-0.90). Treatment effects of statins were statistically insignificant in fatal MI (0.43, 0.09-2.01), stroke (fatal: 0.76, 0.24-2.45; nonfatal: 0.76, 0.53-1.11; total: 0.85, 0.68-1.06) and all-cause mortality (0.96, 0.88-1.04). Significant differences were not observed in myalgia (0.88, 0.69-1.13), elevation of hepatic transaminases (0.98, 0.71-1.34), new-onset diabetes (1.07, 0.77-1.48), serious adverse events (1.00, 0.97-1.04) and discontinuation due to adverse events (1.10, 0.85-1.42). The occurrence of myopathy, rhabdomyolysis and cognitive impairment was largely unreported in the included trials.
CONCLUSIONS
From a risk-benefit perspective, there is a role of statins for the primary prevention of major adverse cardiovascular events in elderly patients. Further studies are needed to ascertain the benefits of statins on fatal MI, stroke and all-cause mortality.
Topics: Aged; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Odds Ratio; Primary Prevention; Randomized Controlled Trials as Topic; Stroke
PubMed: 26245770
DOI: 10.1007/s40266-015-0290-9 -
Systematic Reviews Mar 2023To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and... (Meta-Analysis)
Meta-Analysis
Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools.
BACKGROUND
To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and treatment, and on the accuracy of risk prediction tools for the primary prevention of fragility fractures among adults aged 40 years and older in primary care.
METHODS
For screening effectiveness, accuracy of risk prediction tools, and treatment benefits, our search methods involved integrating studies published up to 2016 from an existing systematic review. Then, to locate more recent studies and any evidence relating to acceptability and treatment harms, we searched online databases (2016 to April 4, 2022 [screening] or to June 1, 2021 [predictive accuracy]; 1995 to June 1, 2021, for acceptability; 2016 to March 2, 2020, for treatment benefits; 2015 to June 24, 2020, for treatment harms), trial registries and gray literature, and hand-searched reviews, guidelines, and the included studies. Two reviewers selected studies, extracted results, and appraised risk of bias, with disagreements resolved by consensus or a third reviewer. The overview of reviews on treatment harms relied on one reviewer, with verification of data by another reviewer to correct errors and omissions. When appropriate, study results were pooled using random effects meta-analysis; otherwise, findings were described narratively. Evidence certainty was rated according to the GRADE approach.
RESULTS
We included 4 randomized controlled trials (RCTs) and 1 controlled clinical trial (CCT) for the benefits and harms of screening, 1 RCT for comparative benefits and harms of different screening strategies, 32 validation cohort studies for the calibration of risk prediction tools (26 of these reporting on the Fracture Risk Assessment Tool without [i.e., clinical FRAX], or with the inclusion of bone mineral density (BMD) results [i.e., FRAX + BMD]), 27 RCTs for the benefits of treatment, 10 systematic reviews for the harms of treatment, and 12 studies for the acceptability of screening or initiating treatment. In females aged 65 years and older who are willing to independently complete a mailed fracture risk questionnaire (referred to as "selected population"), 2-step screening using a risk assessment tool with or without measurement of BMD probably (moderate certainty) reduces the risk of hip fractures (3 RCTs and 1 CCT, n = 43,736, absolute risk reduction [ARD] = 6.2 fewer in 1000, 95% CI 9.0-2.8 fewer, number needed to screen [NNS] = 161) and clinical fragility fractures (3 RCTs, n = 42,009, ARD = 5.9 fewer in 1000, 95% CI 10.9-0.8 fewer, NNS = 169). It probably does not reduce all-cause mortality (2 RCTs and 1 CCT, n = 26,511, ARD = no difference in 1000, 95% CI 7.1 fewer to 5.3 more) and may (low certainty) not affect health-related quality of life. Benefits for fracture outcomes were not replicated in an offer-to-screen population where the rate of response to mailed screening questionnaires was low. For females aged 68-80 years, population screening may not reduce the risk of hip fractures (1 RCT, n = 34,229, ARD = 0.3 fewer in 1000, 95% CI 4.2 fewer to 3.9 more) or clinical fragility fractures (1 RCT, n = 34,229, ARD = 1.0 fewer in 1000, 95% CI 8.0 fewer to 6.0 more) over 5 years of follow-up. The evidence for serious adverse events among all patients and for all outcomes among males and younger females (<65 years) is very uncertain. We defined overdiagnosis as the identification of high risk in individuals who, if not screened, would never have known that they were at risk and would never have experienced a fragility fracture. This was not directly reported in any of the trials. Estimates using data available in the trials suggest that among "selected" females offered screening, 12% of those meeting age-specific treatment thresholds based on clinical FRAX 10-year hip fracture risk, and 19% of those meeting thresholds based on clinical FRAX 10-year major osteoporotic fracture risk, may be overdiagnosed as being at high risk of fracture. Of those identified as being at high clinical FRAX 10-year hip fracture risk and who were referred for BMD assessment, 24% may be overdiagnosed. One RCT (n = 9268) provided evidence comparing 1-step to 2-step screening among postmenopausal females, but the evidence from this trial was very uncertain. For the calibration of risk prediction tools, evidence from three Canadian studies (n = 67,611) without serious risk of bias concerns indicates that clinical FRAX-Canada may be well calibrated for the 10-year prediction of hip fractures (observed-to-expected fracture ratio [O:E] = 1.13, 95% CI 0.74-1.72, I = 89.2%), and is probably well calibrated for the 10-year prediction of clinical fragility fractures (O:E = 1.10, 95% CI 1.01-1.20, I = 50.4%), both leading to some underestimation of the observed risk. Data from these same studies (n = 61,156) showed that FRAX-Canada with BMD may perform poorly to estimate 10-year hip fracture risk (O:E = 1.31, 95% CI 0.91-2.13, I = 92.7%), but is probably well calibrated for the 10-year prediction of clinical fragility fractures, with some underestimation of the observed risk (O:E 1.16, 95% CI 1.12-1.20, I = 0%). The Canadian Association of Radiologists and Osteoporosis Canada Risk Assessment (CAROC) tool may be well calibrated to predict a category of risk for 10-year clinical fractures (low, moderate, or high risk; 1 study, n = 34,060). The evidence for most other tools was limited, or in the case of FRAX tools calibrated for countries other than Canada, very uncertain due to serious risk of bias concerns and large inconsistency in findings across studies. Postmenopausal females in a primary prevention population defined as <50% prevalence of prior fragility fracture (median 16.9%, range 0 to 48% when reported in the trials) and at risk of fragility fracture, treatment with bisphosphonates as a class (median 2 years, range 1-6 years) probably reduces the risk of clinical fragility fractures (19 RCTs, n = 22,482, ARD = 11.1 fewer in 1000, 95% CI 15.0-6.6 fewer, [number needed to treat for an additional beneficial outcome] NNT = 90), and may reduce the risk of hip fractures (14 RCTs, n = 21,038, ARD = 2.9 fewer in 1000, 95% CI 4.6-0.9 fewer, NNT = 345) and clinical vertebral fractures (11 RCTs, n = 8921, ARD = 10.0 fewer in 1000, 95% CI 14.0-3.9 fewer, NNT = 100); it may not reduce all-cause mortality. There is low certainty evidence of little-to-no reduction in hip fractures with any individual bisphosphonate, but all provided evidence of decreased risk of clinical fragility fractures (moderate certainty for alendronate [NNT=68] and zoledronic acid [NNT=50], low certainty for risedronate [NNT=128]) among postmenopausal females. Evidence for an impact on risk of clinical vertebral fractures is very uncertain for alendronate and risedronate; zoledronic acid may reduce the risk of this outcome (4 RCTs, n = 2367, ARD = 18.7 fewer in 1000, 95% CI 25.6-6.6 fewer, NNT = 54) for postmenopausal females. Denosumab probably reduces the risk of clinical fragility fractures (6 RCTs, n = 9473, ARD = 9.1 fewer in 1000, 95% CI 12.1-5.6 fewer, NNT = 110) and clinical vertebral fractures (4 RCTs, n = 8639, ARD = 16.0 fewer in 1000, 95% CI 18.6-12.1 fewer, NNT=62), but may make little-to-no difference in the risk of hip fractures among postmenopausal females. Denosumab probably makes little-to-no difference in the risk of all-cause mortality or health-related quality of life among postmenopausal females. Evidence in males is limited to two trials (1 zoledronic acid, 1 denosumab); in this population, zoledronic acid may make little-to-no difference in the risk of hip or clinical fragility fractures, and evidence for all-cause mortality is very uncertain. The evidence for treatment with denosumab in males is very uncertain for all fracture outcomes (hip, clinical fragility, clinical vertebral) and all-cause mortality. There is moderate certainty evidence that treatment causes a small number of patients to experience a non-serious adverse event, notably non-serious gastrointestinal events (e.g., abdominal pain, reflux) with alendronate (50 RCTs, n = 22,549, ARD = 16.3 more in 1000, 95% CI 2.4-31.3 more, [number needed to treat for an additional harmful outcome] NNH = 61) but not with risedronate; influenza-like symptoms with zoledronic acid (5 RCTs, n = 10,695, ARD = 142.5 more in 1000, 95% CI 105.5-188.5 more, NNH = 7); and non-serious gastrointestinal adverse events (3 RCTs, n = 8454, ARD = 64.5 more in 1000, 95% CI 26.4-13.3 more, NNH = 16), dermatologic adverse events (3 RCTs, n = 8454, ARD = 15.6 more in 1000, 95% CI 7.6-27.0 more, NNH = 64), and infections (any severity; 4 RCTs, n = 8691, ARD = 1.8 more in 1000, 95% CI 0.1-4.0 more, NNH = 556) with denosumab. For serious adverse events overall and specific to stroke and myocardial infarction, treatment with bisphosphonates probably makes little-to-no difference; evidence for other specific serious harms was less certain or not available. There was low certainty evidence for an increased risk for the rare occurrence of atypical femoral fractures (0.06 to 0.08 more in 1000) and osteonecrosis of the jaw (0.22 more in 1000) with bisphosphonates (most evidence for alendronate). The evidence for these rare outcomes and for rebound fractures with denosumab was very uncertain. Younger (lower risk) females have high willingness to be screened. A minority of postmenopausal females at increased risk for fracture may accept treatment. Further, there is large heterogeneity in the level of risk at which patients may be accepting of initiating treatment, and treatment effects appear to be overestimated.
CONCLUSION
An offer of 2-step screening with risk assessment and BMD measurement to selected postmenopausal females with low prevalence of prior fracture probably results in a small reduction in the risk of clinical fragility fracture and hip fracture compared to no screening. These findings were most applicable to the use of clinical FRAX for risk assessment and were not replicated in the offer-to-screen population where the rate of response to mailed screening questionnaires was low. Limited direct evidence on harms of screening were available; using study data to provide estimates, there may be a moderate degree of overdiagnosis of high risk for fracture to consider. The evidence for younger females and males is very limited. The benefits of screening and treatment need to be weighed against the potential for harm; patient views on the acceptability of treatment are highly variable.
SYSTEMATIC REVIEW REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO): CRD42019123767.
Topics: Adult; Female; Humans; Male; Middle Aged; Alendronate; Canada; Denosumab; Diphosphonates; Hip Fractures; Osteoporotic Fractures; Primary Health Care; Primary Prevention; Risedronic Acid; Systematic Reviews as Topic; Zoledronic Acid
PubMed: 36945065
DOI: 10.1186/s13643-023-02181-w -
JAMA Internal Medicine Jan 2018High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.
OBJECTIVE
To assess the association between BP lowering treatment and death and CVD at different BP levels.
DATA SOURCES
Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.
STUDY SELECTION
Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.
DATA EXTRACTION AND SYNTHESIS
Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.
MAIN OUTCOMES AND MEASURES
Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.
RESULTS
Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).
CONCLUSIONS AND RELEVANCE
Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.
Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Global Health; Humans; Incidence; Primary Prevention; Risk Factors; Survival Rate
PubMed: 29131895
DOI: 10.1001/jamainternmed.2017.6015