Does fecal occult blood testing really reduce mortality? A reanalysis of systematic review data

INTRODUCTION: Colorectal cancer (CRC) is a common cause of cancer mortality. A variety of CRC screening strategies are being adopted in many developed countries. Fecal occult blood testing (FOBT) is one option for screening that has the most evidence for efficacy and is also the cheapest approach. Systematic reviews suggest that FOBT is effective in reducing CRC mortality but the data on overall mortality from any cause has rarely been synthesized. METHODS: Randomized controlled trials identified by a Cochrane review of the efficacy of FOBT were reanalyzed. Trials that reported on biennial FOBT with all cause mortality assessed at similar follow-up periods were analyzed. CRC, non-CRC, and all cause mortality were evaluated using a random effects model. RESULTS: Three trials were analyzed, involving 245,217 subjects with 2,148 CRC deaths after almost 3 million patient-years follow-up. The relative risk (RR) of CRC death in the FOBT arm was 0.87 (95% CI = 0.8-0.95). The RR of non-CRC death in the FOBT group was 1.02 (95% CI = 1.00-1.04, p = 0.015). The increase in non-CRC in the FOBT group balanced the decrease in CRC mortality with no overall impact on mortality (RR of dying in the FOBT arm = 1.002, 95% CI = 0.989-1.015). CONCLUSION: The impact of FOBT in reducing mortality from any cause is uncertain and efficacy of this strategy for CRC screening needs reevaluation.     

Review in depth and meta-analysis of controlled trials on colorectal cancer screening by faecal occult blood test

BACKGROUND: Several randomized studies have shown that colorectal cancer (CRC) screening by faecal occult blood test (FOBT) reduces CRC mortality. These trials have different designs, especially concerning FOBT frequency and duration, as well as the length of follow-up after stopping FOBT campaigns. AIMS: To review the effectiveness of screening for CRC with FOBT, to consider the reduction in mortality during or after screening or to identify factors associated with a significant mortality reduction. METHODS: A systematic review of trials of FOBT screening with a meta-analysis of four controlled trials selected for their biennial and population-based design. The main outcome measurements were mortality relative risk (RR) and 95% confidence interval (CI) of biennial FOBT during short (10 years, i.e. five or six rounds) or long-term (six or more rounds) screening periods, as well as after stopping screening and follow-up during 5-7 years. The meta-analysis used the Mantel-Haenszel method with fixed effects when the heterogeneity test was not significant, and used 'intent to screen' results. RESULTS: Although the quality of the four trials was high, only three were randomized, and one used rehydrated biennial FOBT associated with a high colonoscopy rate (28%). A meta-analysis of mortality results showed that subjects allocated to screening had a reduction of CRC mortality during a 10-year period (RR 0.86; CI 0.79-0.94) although CRC mortality was not decreased during the 5-7 years after the 10-year (six rounds) screening period, nor in the last phase (8-16 years after the onset of screening) of a long-term (16 years or nine rounds) biennial screening. Whatever the design of the period of ongoing FOBT, CRC incidence neither decreased nor increased, although it was reduced for 5-7 years after the 10-year screening period. Neither the design nor the clinical or demographic parameters of these trials were independently associated with CRC mortality reduction. CONCLUSION: Biennial FOBT decreased CRC mortality by 14% when performed over 10 years, without evidence-based benefit on CRC mortality when performed over a longer period. No independent predictors of CRC mortality reduction have been identified in order to allow a CRC screening programme in any subgroups of subjects at risk.     

Reduced incidence and mortality from colorectal cancer with flexible-sigmoidoscopy screening: A meta-analysis

AIM: To conduct a systematic review and meta-analysis of published population-based randomized controlled trials (RCTs).METHODS: RCTs evaluating the difference in mortality and incidence of colorectal cancer (CRC) between a screening flexible sigmoidoscopy (FS) group and control group (not assigned to screening FS) with a minimum 5 years median follow-up were identified by a search of MEDLINE and EMBASE databases and the Cochrane Central Register for Controlled Trials through August 2013. Random effects model was used for meta-analysis.RESULTS: Four RCTs with a total of 165659 patients in the FS group and 249707 patients in the control group were included in meta-analysis. Intention-to-treat analysis showed that there was a 22% risk reduction in total incidence of CRC (RR = 0.78, 95%CI: 0.74-0.83), 31% in distal CRC incidence (RR = 0.69, 95%CI: 0.63-0.75), and 9% in proximal CRC incidence (RR = 0.91, 95%CI: 0.83-0.99). Those who underwent screening FS were 18% less likely to be diagnosed with advanced CRC (OR = 0.82, 95%CI: 0.71-0.94). There was a 28% risk reduction in overall CRC mortality (RR = 0.72, 95%CI: 0.65-0.80) and 43% in distal CRC mortality (RR = 0.57, 95%CI: 0.45-0.72).CONCLUSION: This meta-analysis suggests that screening FS can reduce the incidence of proximal and distal CRC and mortality from distal CRC along with reduction in diagnosis of advanced CRC.     

Colorectal cancer screening

Colorectal cancer (CRC) is the third most common cause of cancer death worldwide and a major health problem. In this review, the different approaches for CRC screening will be outlined with emphasis on evidence-based medicine. Evidence from randomized trials on the effectiveness of CRC screening is summarized. Several screening tools for CRC are available. They can be categorized according to their mode of action: early detection tools such as the faecal occult blood test (FOBT) and cancer prevention tools such as flexible sigmoidoscopy and colonoscopy. Meta-analyses of randomized trials show that FOBT screening reduces CRC mortality by 16% (risk ratio 0.84; 95% confidence interval (CI) 0.78-0.9) compared with 30% (risk ratio 0.7; 95% CI 0.6-0.81) for flexible sigmoidoscopy screening. FOBT screening is cheap and noninvasive, but results in large numbers of false-positive tests and needs to be repeated frequently. Flexible sigmoidoscopy is more invasive, but is effective for once-only screening. Although colonoscopy screening is used in some countries, no randomized trials have been conducted to estimate its benefit, and therefore, it should not be recommended at the present time. Faecal occult blood test and flexible sigmoidoscopy are the two CRC screening tools that can be recommended as they have been proven to reduce CRC mortality. Colonoscopy has the potential to be superior to FOBT and flexible sigmoidoscopy, but needs to be evaluated in randomized trials before any recommendation can be provided.     

Protective effect of faecal occult blood test screening for colorectal cancer: worse prognosis for screening refusers.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) by faecal occult blood testing (FOBT) decreases CRC mortality by 15-33%. Compliance remains an obstacle to maximising the benefit of FOBT screening. We tested the hypothesis that individuals offered FOBT screening but refused would have an increased incidence and worse prognosis for CRC compared with those tested and with controls. METHODS: Annual screening was offered to 3548 average risk individuals, > or = 40 years of age, from a highly stable population. A total of 2538 agreed to testing (group 1) and 1010 (28%) refused (group 2). Another 1376 individuals were never offered the test and served as controls (group 3). The groups were followed for 11 years: a three year screening period (1985-1987) and an eight year follow up period at the end of the screening programme (1988-1995). Incidence, stage, and mortality were compared. Characterisation of refusers was completed in 188 and 130 subjects of groups 1 and 2, respectively. RESULTS: In the screening phase, mortality from CRC was significantly lower in group 1 than in groups 2 and 3. The cumulative incidence of CRC in the eight year follow up period was 21 (0.88%), 23 (2.28%), and 13 (0.94%) in groups 1, 2, and 3, respectively. This shows a reduction of 61.4% in group 1 compared with group 2 (relative risk 0.28 (95% confidence interval (CI) 0.19-0.32)) (p<0.001) and 6.4% compared with group 3 (relative risk 0.93 (95% CI 0.93-1.00)) (NS). During follow up, group 1 subjects also demonstrated a decrease in advanced Dukes' stage and mortality rate by 80% and 64%, and 79% and 62%, compared with groups 2 and 3, respectively. Refusers were more likely to be male, of Asian-African descent, and more likely to smoke, consume more coffee, and less tea or dairy foods. CONCLUSIONS: When accepted, FOBT may protect against CRC for prolonged periods. Individuals who refuse FOBT have a significantly higher CRC incidence and mortality rates than those who accept testing.     

Aspirin in the primary prevention of cardiovascular disease on diabetic patients: Systematic review and meta-analysis

AimsThe publication of new trials brought additional data to the controversial topic of aspirin use in diabetic patients for primary prevention. Therefore, we aimed to systematically review all randomized controlled trials evaluating the clinical impact of aspirin in this setting.MethodsWe searched for randomized controlled trials (RCTs) evaluating the impact of aspirin in patients with diabetes in primary prevention, in MEDLINE, EMBASE, CENTRAL (November/2018). The primary outcomes were all-cause mortality and the composite outcome of major adverse cardiovascular events (MACE). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI).ResultsAll-cause mortality was not significantly reduced with RR 0.96 (95% CI 0.90–1.03; 7RCT; 27,595 patients). Regarding MACE, there was an 8% risk reduction (RR 0.92, 95% CI 0.84-0.999; I² = 0%; 8RCT; 29,814 patients). The risks of major bleeding (RR 1.30, 95% CI 1.10–1.53; 2RCTs, 18,019 patients), and major GI bleeding (RR 1.39, 95% CI 1.08–1.80; 2RCTs, 18,019 patients) were significantly increased.The risks of cardiovascular mortality, myocardial infarction, stroke and amputation were not significantly different from control arm.ConclusionsAspirin use among diabetic patients in primary prevention appears was associated with increased risk of major bleeding, a modest decrease of MACE and lack of mortality benefit.     

Effects of pioglitazone on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

AimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. After identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, the experts decided to perform a systematic review and meta-analysis on the effect of pioglitazone with this respect.Data synthesisA MEDLINE database search was performed to identify RCTs, up to June 1st, 2021, with duration≥52 weeks, in which pioglitazone was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH–OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered.Eight RCTs were included in the analysis for MACEs and HF (5048 and 5117 patients in the pioglitazone and control group, respectively), and 24 in that for all-cause mortality (10,682 and 9674 patients). Pioglitazone neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH–OR: 0.90, 95% CI 0.78–1.03, 0.91, 95% CI 0.77, 1.09, and 1.16, 95% CI 0.73, 1.83, respectively). Pioglitazone was associated with a significant reduction of MACE in patients with prior cardiovascular events (MH–OR 0.84, 95% CI 0.72–0.99).ConclusionsThis meta-analysis showed no significant effects of pioglitazone on incident MACE, all-cause mortality, and HHF.     

Long-Term Outcomes of Left Main Coronary Artery Disease Treated With Drug-Eluting Stents vs Coronary Artery Bypass Grafting: A Meta-Analysis and Systematic Review

BackgroundCurrently, DES is a reasonable treatment option for LMCA disease but CABG continues to be first-line treatment. Multiple randomized clinical trials (RCTs) have compared outcomes between these two treatment modalities. Recently, these trials published their long-term results with conflicting findings.MethodsWe conducted a systematic review and meta-analysis of RCTs that compared DES vs CABG in patients with LMCA disease. We only included trials with follow up duration of at least 5 years. The primary outcome was all-cause mortality. Secondary outcomes included risk of cardiac death, myocardial infarction (MI), stroke and repeat revascularization.ResultsWe included a total of 4 RCTs. The median-weighted follow up period was 6.5 years. There was no significant difference between DES and CABG in all-cause mortality (Risk ratio (RR) 1.10; 95% confidence interval (CI) 0.92 to 1.31; p = 0.28), risk of cardiac death (RR of 1.08, 95% CI 0.84 to 1.38; p = 0.56), total MI (RR of 1.22, 95% CI 0.96 to 1.56; p = 0.11), and stroke (RR of 0.85, 95% CI 0.46 to 1.57; p = 0.60). The risk of repeat revascularization (RR of 1.75, 95% CI 1.50 to 2.03; p < 0.00001), and non-periprocedural MI (RR of 2.13, 95% CI 1.53 to 2.97; p < 0.00001) were significantly higher in the DES arm.ConclusionsDES has similar long-term outcomes compared to CABG in terms of all-cause mortality, cardiac death, total MI and stroke; but was associated with a higher risk of repeat revascularization, and non-periprocedural MI.     

Effectiveness of Mobile Health Technology Interventions for Patients With Heart Failure: Systematic Review and Meta-analysis

BackgroundHeart failure (HF) is a complex and serious condition associated with substantial morbidity, mortality, and health care costs. We conducted a systematic review and meta-analysis to evaluate the effects of mobile health (mHealth) interventions compared with usual care in patients with HF.MethodsWe searched MEDLINE, CENTRAL, CINAHL, and EMBASE databases to identify eligible randomized controlled trials (RCTs) of mHealth interventions. Primary outcomes included: all-cause mortality, cardiovascular mortality, HF-related hospitalizations, and all-cause hospitalizations. Meta-analyses using a random effects model were performed for all outcomes. Risk of bias and quality of evidence were evaluated using the Cochrane Tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.ResultsSixteen RCTs involving 4389 patients were included. Compared with usual care, mHealth interventions reduced the risk of all-cause mortality (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.65-0.97; absolute risk reduction [ARR], 2.1%; high-quality evidence), cardiovascular mortality (RR, 0.70; 95% CI, 0.53-0.91; ARR, 2.9%; high-quality evidence), and HF hospitalizations (RR, 0.77; 95% CI, 0.67-0.88; ARR, 5%; high-quality evidence), but had no effect on all-cause hospitalizations. Results were driven by mHealth interventions with remote monitoring and clinical feedback, which were associated with larger reductions than stand-alone mHealth interventions. However, subgroup differences were not statistically significant.ConclusionsmHealth interventions with remote monitoring and clinical feedback reduce mortality and HF-related hospitalizations, but might not reduce all-cause hospitalizations in patients with HF. Additional studies are needed to determine the efficacy of stand-alone mHealth interventions as well as active features of mHealth that contribute to efficacy.     

Reasons for intentional weight loss, unintentional weight loss, and mortality in older men

BACKGROUND: We have examined the relationship between intentional and unintentional weight loss and the reasons underlying intention to lose weight and all-cause mortality and mortality due to cardiovascular disease (CVD) and non-CVD causes in older men. METHODS: Prospective study of 4869 men aged 56 to 75 years drawn from general practices in 24 British towns, who in 1996 completed questionnaires about intentional and unintentional weight loss over the preceding 4 years and were followed up for a subsequent 7 years. RESULTS: Unintentional but not intentional weight loss was associated with a significant increase in risk of all-cause mortality compared with men who reported no weight change, even after adjustment for lifestyle characteristics and preexisting disease (adjusted relative risk [RR], 1.71; 95% confidence interval [CI], 1.33-2.19; and RR, 1.00; 95% CI, 0.91-1.10, respectively). Men who lost weight intentionally as a result of personal choice showed significant benefit in all-cause mortality (RR, 0.59; 95% CI, 0.34-1.00; P = .05), which was largely owing to a significant reduction in mortality from non-CVD causes (RR, 0.36; 95% CI, 0.15-0.87). The benefit in these men was most apparent in markedly overweight men (BMI [calculated as weight in kilograms divided by the square of height in meters] > or = 28) and in younger men (age < 65 years). Men who lost weight intentionally owing to ill health or physician's advice showed an increased risk of all-cause mortality (RR, 1.37; 95% CI, 0.96-1.94). No harm or benefit was seen for CVD mortality, irrespective of reasons for intentional weight loss. CONCLUSION: Intentional weight loss carried out for personal reasons is associated with a significant reduction in all-cause mortality in markedly overweight men, and the data suggest that the earlier the intervention, the greater the chance of benefit.     

Survival After Coronary Revascularization With Paclitaxel-Coated Balloons

BackgroundDrug-coated balloons (DCBs) are accepted treatment strategies for coronary in-stent restenosis and are under clinical investigation for lesions without prior stent implantation. A recently published meta-analysis suggested an increased risk of death associated with the use of paclitaxel-coated devices in the superficial femoral artery. The reasons are incompletely understood as potential underlying pathomechanisms remain elusive, and no relationship to the administered dose has been documented.ObjectivesThe purpose of this analysis was to investigate the available data on survival after coronary intervention with paclitaxel-coated balloons from randomized controlled trials (RCTs).MethodsPubMed, Web of science, and the Cochrane library database were searched, and a meta-analysis from RCT was performed comparing DCB with non-DCB devices (such as conventional balloon angioplasty, bare-metal stents, or drug-eluting stents) for the treatment of coronary in-stent restenosis or de novo lesions. The primary outcome was all-cause death. The number of patients lost to follow-up was observed at different time points. Risk estimates are reported as risk ratios (RRs) with 95% confidence intervals (CIs).ResultsA total of 4,590 patients enrolled in 26 RCTs published between 2006 and 2019 were analyzed. At follow-up of 6 to 12 months, no significant difference in all-cause mortality was found, however, with numerically lower rates after DCB treatment (RR: 0.74; 95% CI: 0.51 to 1.08; p = 0.116). Risk of death at 2 years (n = 1,477, 8 RCTs) was similar between the 2 groups (RR: 0.84; 95% CI: 0.51 to 1.37; p = 0.478). After 3 years of follow-up (n = 1,775, 9 RCTs), all-cause mortality was significantly lower in the DCB group when compared with control treatment (RR: 0.73; 95% CI: 0.53 to 1.00; p = 0.047) with a number needed to treat of 36 to prevent 1 death. A similar reduction was seen in cardiac mortality (RR: 0.53; 95% CI: 0.33 to 0.85; p = 0.009).ConclusionsIn this meta-analysis, the use of paclitaxel DCBs for treatment of coronary artery disease was not associated with increased mortality, as has been suggested for peripheral arteries. On the contrary, use of coronary paclitaxel-coated balloons was associated with a trend toward lower mortality when compared with control treatments.     

Effect of aspirin on mortality in the primary prevention of cardiovascular disease

Objective

The lack of a mortality benefit of aspirin in prior meta-analyses of primary prevention trials of cardiovascular disease has contributed to uncertainty about the balance of benefits and risks of aspirin in primary prevention. We performed an updated meta-analysis of randomized controlled trials of aspirin to obtain best estimates of the effect of aspirin on mortality in primary prevention.

Methods

Eligible articles were identified by searches of electronic databases and reference lists. Outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and bleeding. Data were pooled from individual trials using the DerSimonian-Laird random-effects model, and results are presented as relative risk (RR) and 95% confidence intervals (CIs).

Results

Nine randomized controlled trials enrolling 100,076 participants were included. Aspirin reduced all-cause mortality (RR 0.94; 95% CI, 0.88-1.00), myocardial infarction (RR 0.83; 95% CI, 0.69-1.00), ischemic stroke (RR 0.86; 95% CI, 0.75-0.98), and the composite of myocardial infarction, stroke, or cardiovascular death (RR 0.88; 95% CI, 0.83-0.94), but did not reduce cardiovascular mortality (RR 0.96; 95% CI, 0.84-1.09). Aspirin increased the risk of hemorrhagic stroke (RR 1.36; 95% CI, 1.01-1.82), major bleeding (RR 1.66; 95% CI, 1.41-1.95), and gastrointestinal bleeding (RR 1.37; 95% CI, 1.15-1.62). A lack of availability of patient-level data precluded exploration of benefits and risks of aspirin in key subgroups.

Conclusion

Aspirin prevents deaths, myocardial infarction, and ischemic stroke, and increases hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease.     

抗血小板与抗凝治疗预防非瓣膜性心房颤动缺血性卒中的疗效评价

目的 评价抗血小板治疗与抗凝治疗预防非瓣膜性心房颤动(房颤)缺血性卒中疗效及安全性.方法 采用Cochrane系统评价方法,计算机检索PubMed、Embase、CENTREN及其下属各临床注册试验数据中心、中国生物医学文献数据库、中文科技期刊数据库、中国期刊全文数据库,检索时间截至2009年12月,纳入中外文抗血小板治疗与抗凝治疗预防非瓣膜性房颤缺血性卒中随机对照试验(RCT).由两名评价者独立评价纳入研究质量、提取资料并交叉核对.采用RevMan 5.0软件进行荟萃分析.结果 共纳入14个RCT,包括15 880例患者.荟萃分析结果显示:与对照组比较,抗血小板治疗不减少非瓣膜性房颤缺血性卒中(RR=0.83,95%CI0.68～1.00,P=0.05),不减少房颤全因死亡(RR=0.88,95% CI 0.73～1.07,P=0.21),可能增加房颤患者严重出血1.9倍(RR=2.88,95%CI1.21～6.86,P=0.02),不减少房颤体循环栓塞(RR=0.71,95%CI0.34～1.51,P=0.38),不增加房颤患者颅内出血(RR=3.25,95%CI0.84～12.62,P=0.09).抗血小板治疗与抗凝治疗比较显示:抗凝治疗显著降低房颤缺血性卒中发生率(RR=1.84,95%CI1.48～2.28,P＜0.01),房颤全因病死率二者差异无统计学意义(RR=1.06,95%CI0.90～1.23,P=0.50),严重出血发生率二者差异无统计学意义(RR=0.95,95%CI0.76～1.19,P=0.66),抗凝治疗显著降低房颤体循环栓塞发生率(RR=1.94,95%CI1.24～3.03,P=0.004),抗凝治疗显著增加颅内出血发生率(RR=0.49,95%CI0.31～0.78,P=0.003).结论 与对照组比较,抗血小板治疗不减少非瓣膜性房颤缺血性卒中及体循环栓塞,并可能增加房颤严重出血事件1.9倍;抗血小板治疗与抗凝治疗比较,抗凝治疗显著降低房颤缺血性卒中及体循环栓塞发生率,不增加房颤严重出血但显著增加颅内出血发生率.由于纳入的研究有限,结局指标不够统一,得出的结论尚需更多设计严谨、使用统一结局指标、随访时间较长的大样本RCT来进一步证实.

Abstract：

Objective To evaluate the efficacy and security of anti-platelet and anticoagulant therapy on prevention of ischemic stroke in patients with nonvalvular atrial fibrillation ( NAF). Methods We searched PubMed, EMbase, CENTREN and its affiliated clinical trial registration data center, CBMdisc,VIP,and CNKI databases from establishment to Dec 2009 to identify randomized controlled trials (RCTs)covering the use of anti-platelet agents and anticoagulants for patients with NAF. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included RCTs. Results Fourteen RCTs involving 15 880 patients were include. Compared with placebo or no use of anti-platelet drugs, antiplatelet therapy didn't reduce ischemic stroke (RR = 0. 83,95% CI0. 68 to 1.00, P = 0. 05 ), systemic emboli ( RR= 0. 71, 95% CI0. 34 to 1.51, P = 0. 38 ) and all-cause mortality (RR = 0. 88, 95% CI0. 73 to 1.07, P= 0. 21 ) while significantly increased the major bleeding ( RR = 2. 88, 95% CI 1.21 to 6. 86, P= 0. 02 ) in patients with NAF, intracranial hemorrhage was not affected by antiplatelet therapy in patients with atrial fibrillation ( RR= 3. 25, 95% CI0. 84 to 12.62, P =0. 09). Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the incidence of ischemic stroke (RR = 1.84,95% CI 1.48 to 2. 28 ,P ＜0. 01 ) and systemic emboli (RR= 1.94, 95% CI 1.24 to 3.03, P = 0. 004 ) but significantly increased the incidence of intracranial hemorrhage ( RR =0. 49, 95% CI0. 31 to 0. 78, P= 0. 003 ), did not affect all-cause mortality ( RR = 1.06, 95% CI0. 90 to 1.23, P = 0. 50) and the incidence of major bleeding ( RR = 0. 95, 95 % CI0. 76 to 1.19, P = 0. 66) in NAF patients. Conclusions Compared with the placebo and no use of anti-platelet drugs, anti-platelet therapy didn't reduce ischemic stroke and systemic emboli but increased the risk of major bleeding in NAF patients. Compared with anti-platelet therapy, anticoagulant therapy significantly reduced the ischemic stroke and systemic emboli without increasing the risk of major bleeding, but significantly increased the incidence of intracranial hemorrhage in NAF patients. Since the study included RCTs with limited and less uniform outcome endpoints, the conclusions should be verified with RCTs with more uniform endpoints and longer follow-up time.     

Rescue angioplasty or repeat fibrinolysis after failed fibrinolytic therapy for ST-segment myocardial infarction: a meta-analysis of randomized trials.

OBJECTIVES: We sought to best estimate the benefits and risks associated with rescue percutaneous coronary intervention (PCI) and repeat fibrinolytic therapy as compared with conservative management in patients with failed fibrinolytic therapy for ST-segment myocardial infarction (STEMI). BACKGROUND: Fibrinolytic therapy is the most common treatment for STEMI; however, the best therapy in patients who fail to achieve reperfusion after fibrinolytic therapy remains uncertain. METHODS: We performed a meta-analysis of randomized trials using a fixed-effects model. We included 8 trials enrolling 1,177 patients with follow-up duration ranging from hospital discharge to 6 months. RESULTS: Rescue PCI was associated with no significant reduction in all-cause mortality (relative risk [RR] 0.69; 95% confidence interval [CI] 0.46 to 1.05), but was associated with significant risk reductions in heart failure (RR 0.73; 95% CI 0.54 to 1.00) and reinfarction (RR 0.58; 95% CI 0.35 to 0.97) when compared with conservative treatment. Rescue PCI was associated with an increased risk of stroke (RR 4.98; 95% CI 1.10 to 22.5) and minor bleeding (RR 4.58; 95% CI 2.46 to 8.55). Repeat fibrinolytic therapy was not associated with significant improvements in all-cause mortality (RR 0.68; 95% CI 0.41 to 1.14) or reinfarction (RR 1.79; 95% CI 0.92 to 3.48), but was associated with an increased risk for minor bleeding (RR 1.84; 95% CI 1.06 to 3.18). CONCLUSIONS: Rescue PCI is associated with improved clinical outcomes for STEMI patients after failed fibrinolytic therapy, but these benefits must be interpreted in the context of potential risks. On the other hand, repeat fibrinolytic therapy is not associated with significant clinical improvement and may be associated with increased harm.     

Body mass index and colorectal cancer prognosis: a systematic review and meta-analysis

Colorectal cancer is one of the most common cancers worldwide. However, it is unclear what influence body mass index (BMI) has on colorectal cancer prognosis. We conducted a systematic review and meta-analysis of observational studies to examine the association of BMI with colorectal cancer outcomes. We searched MEDLINE and EMBASE databases from inception to February 2015 and references of identified articles. We selected observational studies that reported all-cause mortality, colorectal cancer-specific mortality, recurrence and disease-free survival according to BMI category. Random-effects meta-analyses were conducted to combine estimates. We included 18 observational studies. Obese patients had an increased risk of all-cause mortality [relative risk (RR) 1.14; 95 % confidence interval (CI) 1.07–1.21], cancer-specific mortality (RR 1.14; 95 % CI 1.05–1.24), recurrence (RR 1.07; 95 % CI 1.02–1.13) and worse disease-free survival (RR 1.07; 95 % CI 1.01–1.13). Underweight patients also had an increased risk of all-cause mortality (RR 1.43; 95 % CI 1.26–1.62), cancer-specific mortality (RR 1.50; 95 % CI 1.20–1.87), recurrence (RR 1.13; 95 % CI 1.05–1.21) and worse disease-free survival (RR 1.27; 95 % CI 1.13–1.43). Overweight patients had no increased risk for any of the outcomes studied. Both obese and underweight patients with colorectal cancer have an increased risk of all-cause mortality, cancer-specific mortality, disease recurrence and worse disease-free survival compared to normal weight patients.     

Prolactin Inhibition in Peripartum Cardiomyopathy: Systematic Review and Meta-analysis

Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all HF in pregnancy. Cardiac angiogenic imbalance caused by cleaved 16kDa prolactin has been hypothesized to contribute to the development of PPCM, fueling investigation of prolactin inhibitors for the management of PPCM. We conducted a systematic review and meta-analysis to assess the impact of prolactin inhibition on left ventricular (LV) function and mortality in patients with PPCM. We included English language articles from PubMed and EMBASE published upto March 2022. We pooled the mean difference (MD) for left ventricular ejection fraction (LVEF) at follow-up, odds ratio (OR) for LV recovery and risk ratio (RR) for all-cause mortality using random-effects meta-analysis. Among 548 studies screened, 10 studies (3 randomized control trials (RCTs), 2 retrospective and 5 prospective cohorts) were included in the systematic review. Patients in the Bromocriptine + standard guideline directed medical therapy (GDMT) group had higher LVEF% (pMD 12.56 (95% CI 5.84-19.28, I2=0%) from two cohorts and pMD 14.25 (95% CI 0.61-27.89, I2=88%) from two RCTs) at follow-up compared to standard GDMT alone group. Bromocriptine group also had higher odds of LV recovery (pOR 3.55 (95% CI 1.39-9.1, I2=62)). We did not find any difference in all-cause mortality between the groups. Our analysis demonstrates that the addition of Bromocriptine to standard GDMT was associated with a significant improvement in LVEF% and greater odds of LV recovery, without significant reduction in all-cause mortality.     

Effects of renin-angiotensin system blockers on renal outcomes and all-cause mortality in patients with diabetic nephropathy: an updated meta-analysis

BackgroundIn contrast to previous studies, recent data questioned the ability of renin-angiotensin-aldosterone system (RAAS) blockers to delay progression of diabetic nephropathy. This study evaluated the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients with diabetic nephropathy.MethodsA systematic literature search of MEDLINE/PubMed and EMBASE databases was performed to identify randomized trials published up to June 2007 comparing the effects of ACEIs or ARBs with placebo and/or a regimen not including a RAAS blocker on the incidence of end-stage renal disease (ESRD), doubling of serum creatinine (DSC), or death from any cause in patients with diabetic nephropathy. Treatment effects were summarized as relative risks (RRs) using the Mantel-Haenszel fixed-effects model.ResultsOf the 1,028 originally identified studies, 24 fulfilled the inclusion criteria (20 using ACEIs and 4 using ARBs). Use of ACEIs was associated with a trend toward reduction of ESRD incidence (RR 0.70; 95% confidence interval (CI) 0.46-1.05) and use of ARBs with significant reduction of ESRD risk (RR 0.78; 95% CI 0.67-0.91). Both drug classes were associated with reduction in the risk of DSC (RR 0.71; 95% CI 0.56-0.91 for ACEIs and RR 0.79; 95% CI 0.68-0.91 for ARBs) but none affected all-cause mortality (RR 0.96; 95% CI 0.85-1.09 for ACEIs and RR 0.99; 95% CI 0.85-1.16 for ARBs).ConclusionTreatment of patients with diabetic nephropathy with a RAAS blocker reduces the risks of ESRD and DSC, but does not affect all-cause mortality. These findings are added to the evidence of a renoprotective role of RAAS blockers in such patients.American Journal of Hypertension (2008). doi:10.1038/ajh.2008.206American Journal of Hypertension (2008); 21, 8, 922-929. doi:10.1038/ajh.2008.206.     

Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation

New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.     

Mortality reduction by implantable cardioverter-defibrillators in high-risk patients with heart failure, ischemic heart disease, and new-onset ventricular arrhythmia: an effectiveness study

OBJECTIVES: To investigate the generalizability of the reduction in mortality posed by implantable cardioverter-defibrillators, we examined the effectiveness of defibrillators as applied in routine medical practice. BACKGROUND: Implantable cardioverter-defibrillators have been shown to be efficacious in the primary and secondary prevention of overall and cardiovascular mortality in clinical trials. METHODS: Using the National Veterans Administration database, we identified a cohort of 6,996 patients from 1995 to 1999 with new-onset ventricular arrhythmia and pre-existing ischemic heart disease and congestive heart failure, of which 1,442 received a defibrillator, and followed them for three years to determine rates of mortality. With multivariate logistic regression analyses that adjusted for demographics, illness severity, and comorbidity, we assessed overall, cardiovascular, and noncardiovascular rates of mortality. To further address potential confounding, we also stratified the cohort by quintiles using a multivariable propensity score for each patient and determined mortality rates. RESULTS: For the overall cohort, multivariate regression showed that those who received defibrillators had significantly lower all-cause (odds ratio [OR] 0.52; 95% confidence interval [CI] 0.45 to 0.60) and cardiovascular (OR 0.56; 95% CI 0.49 to 0.65)] rates of mortality at three years. No significant differences were noted between groups in their rates of noncardiovascular mortality (OR 0.92; 95% CI 0.77 to 1.10). Propensity score analysis demonstrated similar mortality reduction benefits at three years: risk ratio (RR) 0.72 (95% CI 0.69 to 0.79) for all-cause; RR 0.70 (95% CI 0.63 to 0.78) for cardiovascular; and RR 0.95 (95% CI 0.83 to 1.08) for noncardiovascular rates of mortality. These results suggest that one death is prevented in this patient population for every four to five patients receiving a defibrillator for three years. CONCLUSIONS: Implantable cardioverter-defibrillators in routine medical practice significantly reduce cardiovascular and all-cause rates of mortality at levels similar to secondary prevention trials.     

Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis.

OBJECTIVES: This study was designed to determine whether statins reduce all-cause mortality in elderly patients with coronary heart disease. BACKGROUND: Statins continue to be underutilized in elderly patients because evidence has not consistently shown that they reduce mortality. METHODS: We searched 5 electronic databases, the Internet, and conference proceedings to identify relevant trials. In addition, we obtained unpublished data for the elderly patient subgroups from 4 trials and for the secondary prevention subgroup from the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) trial. Inclusion criteria were randomized allocation to statin or placebo, documented coronary heart disease, > or =50 elderly patients (defined as age > or =65 years), and > or =6 months of follow-up. Data were analyzed with hierarchical Bayesian modeling. RESULTS: We included 9 trials encompassing 19,569 patients with an age range of 65 to 82 years. Pooled rates of all-cause mortality were 15.6% with statins and 18.7% with placebo. We estimated a relative risk reduction of 22% over 5 years (relative risk [RR] 0.78; 95% credible interval [CI] 0.65 to 0.89). Furthermore, statins reduced coronary heart disease mortality by 30% (RR 0.70; 95% CI 0.53 to 0.83), nonfatal myocardial infarction by 26% (RR 0.74; 95% CI 0.60 to 0.89), need for revascularization by 30% (RR 0.70; 95% CI 0.53 to 0.83), and stroke by 25% (RR 0.75; 95% CI 0.56 to 0.94). The posterior median estimate of the number needed to treat to save 1 life was 28 (95% CI 15 to 56). CONCLUSIONS: Statins reduce all-cause mortality in elderly patients and the magnitude of this effect is substantially larger than had been previously estimated.