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Objective: To determine the relative efficacy of structured named diet and health behaviour programmes (dietary programmes) for prevention of mortality and major cardiovascular events in patients at increased risk of cardiovascular disease., Design: Systematic review and network meta-analysis of randomised controlled trials., Data Sources: AMED (Allied and Complementary Medicine Database), CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ClinicalTrials.gov were searched up to September 2021., Study Selection: Randomised trials of patients at increased risk of cardiovascular disease that compared dietary programmes with minimal intervention (eg, healthy diet brochure) or alternative programmes with at least nine months of follow-up and reporting on mortality or major cardiovascular events (such as stroke or non-fatal myocardial infarction). In addition to dietary intervention, dietary programmes could also include exercise, behavioural support, and other secondary interventions such as drug treatment., Outcomes and Measures: All cause mortality, cardiovascular mortality, and individual cardiovascular events (stroke, non-fatal myocardial infarction, and unplanned cardiovascular interventions)., Review Methods: Pairs of reviewers independently extracted data and assessed risk of bias. A random effects network meta-analysis was performed using a frequentist approach and grading of recommendations assessment, development and evaluation (GRADE) methods to determine the certainty of evidence for each outcome., Results: 40 eligible trials were identified with 35 548 participants across seven named dietary programmes (low fat, 18 studies; Mediterranean, 12; very low fat, 6; modified fat, 4; combined low fat and low sodium, 3; Ornish, 3; Pritikin, 1). At last reported follow-up, based on moderate certainty evidence, Mediterranean dietary programmes proved superior to minimal intervention for the prevention of all cause mortality (odds ratio 0.72, 95% confidence interval 0.56 to 0.92; patients at intermediate risk: risk difference 17 fewer per 1000 followed over five years), cardiovascular mortality (0.55, 0.39 to 0.78; 13 fewer per 1000), stroke (0.65, 0.46 to 0.93; 7 fewer per 1000), and non-fatal myocardial infarction (0.48, 0.36 to 0.65; 17 fewer per 1000). Based on moderate certainty evidence, low fat programmes proved superior to minimal intervention for prevention of all cause mortality (0.84, 0.74 to 0.95; 9 fewer per 1000) and non-fatal myocardial infarction (0.77, 0.61 to 0.96; 7 fewer per 1000). The absolute effects for both dietary programmes were more pronounced for patients at high risk. There were no convincing differences between Mediterranean and low fat programmes for mortality or non-fatal myocardial infarction. The five remaining dietary programmes generally had little or no benefit compared with minimal intervention typically based on low to moderate certainty evidence., Conclusions: Moderate certainty evidence shows that programmes promoting Mediterranean and low fat diets, with or without physical activity or other interventions, reduce all cause mortality and non-fatal myocardial infarction in patients with increased cardiovascular risk. Mediterranean programmes are also likely to reduce stroke risk. Generally, other named dietary programmes were not superior to minimal intervention., Systematic Review Registration: PROSPERO CRD42016047939., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Dalhousie University for the submitted work; no other relationships or activities that could appear to have influenced the submitted work. BCJ received a grant from Texas A&M AgriLife Research to fund investigator initiated research related to saturated and polyunsaturated fats. The grant was from Texas A&M AgriLife institutional funds from interest and investment earnings, not a sponsoring organisation, industry, or company., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement., Background: Few randomized trials have evaluated the effect of reducing red meat intake on clinically important outcomes., Purpose: To summarize the effect of lower versus higher red meat intake on the incidence of cardiometabolic and cancer outcomes in adults., Data Sources: EMBASE, CENTRAL, CINAHL, Web of Science, and ProQuest from inception to July 2018 and MEDLINE from inception to April 2019, without language restrictions., Study Selection: Randomized trials (published in any language) comparing diets lower in red meat with diets higher in red meat that differed by a gradient of at least 1 serving per week for 6 months or more., Data Extraction: Teams of 2 reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence., Data Synthesis: Of 12 eligible trials, a single trial enrolling 48 835 women provided the most credible, though still low-certainty, evidence that diets lower in red meat may have little or no effect on all-cause mortality (hazard ratio [HR], 0.99 [95% CI, 0.95 to 1.03]), cardiovascular mortality (HR, 0.98 [CI, 0.91 to 1.06]), and cardiovascular disease (HR, 0.99 [CI, 0.94 to 1.05]). That trial also provided low- to very-low-certainty evidence that diets lower in red meat may have little or no effect on total cancer mortality (HR, 0.95 [CI, 0.89 to 1.01]) and the incidence of cancer, including colorectal cancer (HR, 1.04 [CI, 0.90 to 1.20]) and breast cancer (HR, 0.97 [0.90 to 1.04])., Limitations: There were few trials, most addressing only surrogate outcomes, with heterogeneous comparators and small gradients in red meat consumption between lower versus higher intake groups., Conclusion: Low- to very-low-certainty evidence suggests that diets restricted in red meat may have little or no effect on major cardiometabolic outcomes and cancer mortality and incidence., Primary Funding Source: None (PROSPERO: CRD42017074074).

This article has been corrected. The original version (PDF) is appended to this article as a Supplement., Background: Studying dietary patterns may provide insights into the potential effects of red and processed meat on health outcomes., Purpose: To evaluate the effect of dietary patterns, including different amounts of red or processed meat, on all-cause mortality, cardiometabolic outcomes, and cancer incidence and mortality., Data Sources: Systematic search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and ProQuest Dissertations & Theses Global from inception to April 2019 with no restrictions on year or language., Study Selection: Teams of 2 reviewers independently screened search results and included prospective cohort studies with 1000 or more participants that reported on the association between dietary patterns and health outcomes., Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria., Data Synthesis: Eligible studies that followed patients for 2 to 34 years revealed low- to very-low-certainty evidence that dietary patterns lower in red and processed meat intake result in very small or possibly small decreases in all-cause mortality, cancer mortality and incidence, cardiovascular mortality, nonfatal coronary heart disease, fatal and nonfatal myocardial infarction, and type 2 diabetes. For all-cause, cancer, and cardiovascular mortality and incidence of some types of cancer, the total sample included more than 400 000 patients; for other outcomes, total samples included 4000 to more than 300 000 patients., Limitation: Observational studies are prone to residual confounding, and these studies provide low- or very-low-certainty evidence according to the GRADE criteria., Conclusion: Low- or very-low-certainty evidence suggests that dietary patterns with less red and processed meat intake may result in very small reductions in adverse cardiometabolic and cancer outcomes., Primary Funding Source: None. (PROSPERO: CRD42017074074).

Ezetimibe is widely used in combination with statins to reduce low-density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient-important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6 months and reported on at least one of all-cause mortality, cardiovascular deaths, non-fatal myocardial infarctions (MI), and non-fatal strokes were included. Pairs of reviewers extracted study data and assessed risk of bias independently and in duplicate. Quality of evidence was assessed using the GRADE approach. We conducted a narrative review with complementary subgroup and sensitivity analyses. IMPROVE-IT study enrolled 93% of all patients enrolled in the 8 included trials. Our analysis of the IMPROVE-IT study results showed that in patients at high risk of cardiovascular events, ezetimibe added to statins was associated with i) a likely reduction in non-fatal MI (17 fewer/1000 treated over 6 years, moderate certainty in evidence); ii) a possible reduction in non-fatal stroke (6 fewer/1000 treated over 6 years, low certainty); iii) no impact on myopathy (moderate certainty); iv) potentially no impact on all-cause mortality and cardiovascular death (both moderate certainty); and v) possibly no impact on cancer (low certainty). Addition of ezetimibe to moderate-dose statins is likely to result in 17 fewer MIs and possibly 6 fewer strokes/1000 treated over 6 years but is unlikely to reduce all-cause mortality or cardiovascular death. Patients who place a high value on a small absolute reduction in MI and are not adverse to use of an additional medication over a long duration may opt for ezetimibe in addition to statin therapy. Our analysis revealed no increased specific harms associated with addition of ezetimibe to statins., (© 2017 John Wiley & Sons, Ltd.)