Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? 

Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.

Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4

Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?

A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

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Measuring inconsistency in meta-analyses

Systematic review and meta-analysis

Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users.

Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions.

The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

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The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration

"The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of
more than 140 mm Hg is a much more important cardiovascular disease
(CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75
mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive
at 55 years of age have a 90% lifetime risk for developing hypertension; (3)
Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80
to 89 mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should
be used in drug treatment for most patients with uncomplicated hypertension,
either alone or combined with drugs from other classes. Certain high-risk
conditions are compelling indications for the initial use of other antihypertensive
drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
blockers, β-blockers, calcium channel blockers); (5) Most patients with
hypertension will require 2 or more antihypertensive medications to achieve
goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes
or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal
BP, consideration should be given to initiating therapy with 2 agents, 1 of
which usually should be a thiazide-type diuretic; and (7) The most effective
therapy prescribed by the most careful clinician will control hypertension
only if patients are motivated. Motivation improves when patients have positive
experiences with and trust in the clinician. Empathy builds trust and is a
potent motivator. Finally, in presenting these guidelines, the committee recognizes
that the responsible physician's judgment remains paramount.

https://jamanetwork.com/journals/jama/articlepdf/196589/JSC30096.pdf

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

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Cochrane Handbook for Systematic Reviews of Interventions

Ideal cardiovascular health is associated with a decrease in adverse cardiovascular events. The My Research Legacy study examined ideal cardiovascular health using the Life's Simple 7 survey and data from digital health devices. We hypothesized that digital devices provide a more objective view of overall cardiovascular health status than self-reported measures. Therefore, we analyzed weight and activity data recorded by digital devices to recalculate the Life's Simple 7 Health Score. All study participants (n = 1561) answered the survey, while a subgroup (n = 390) provided data from digital devices. Individuals with digital devices had a lower body mass index (BMI) and higher weekly minutes of vigorous exercise than participants without digital devices (p < 0.01). Baseline Health Scores were higher in individuals with digital devices compared to those without (7.0 ± 1.6 vs. 6.6 ± 1.6, p < 0.01). Data from digital devices reveal both increases and decreases in measured vs. self-reported BMI (p < 0.04) and weekly minutes of moderate and vigorous exercise activity (p < 0.01). Using these data, a significant difference was found between the recalculated and the self-reported Life's Simple 7 Health Score (p < 0.05). These findings suggest that incorporation of digital health devices should be considered as part of a precision medicinal approach to assessing ideal cardiovascular health.

https://www.mdpi.com/2075-4426/11/3/189/pdf

Data from Digital Health Devices Informs Ideal Cardiovascular Health.

Abstract 1999: Angiographic and Clinical Outcomes Among Patients with Acute Coronary Syndrome Presenting with Isolated Anterior ST-Segment Depressions

Clinical trials over the last several decades provide a roadmap for managing an acute coronary syndrome (ACS). Clinical practice guidelines from professional societies codified the findings of such trials into recommendations for management of the patient with an ACS event. It is of interest to evaluate the long-term impact of ACS management strategies with particular attention to the changes brought about by serial expansion of the ACS therapeutic armamentarium. Longitudinal assessments of therapies for ACS cannot be derived from clinical trials, which by definition are confined to a particular era in time. Instead, observational data must be used, and it would be desirable if the source of those data is comprehensive and stable over time. The Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) is an ideal registry to conduct such analyses. All 72 hospitals in Sweden providing care for patients with cardiac diseases participate in SWEDEHEART and data can be linked to national patient registries and compared with general population statistics in Sweden. Using a sophisticated epidemiological approach, Szummer et al. previously reported improved outcomes in 105 674 patients with ST-elevation myocardial infarction (STEMI) tracked in SWEDEHEART between 1995 and 2014. The 20-year interval was divided into 2-year blocks and the percentages of STEMI patients receiving key treatments [beta-blockers, reperfusion, angiotensinconverting enzyme inhibitors/angiotensin receptor blockers (ACEI/ ARBs), statins, coronary angiography, primary percutaneous corronary intervention (PCI), and in-hospital coronary artery bypass graft (CABG)] were plotted. Total mortality and cardiovascular deaths decreased over time, roughly paralleling the time course of increased use of evidence-based treatments. Standardized incidence ratios for events compared with the general population and regression analyses adjusting for demographic changes over time also showed improvements in cardiovascular outcomes in association with greater use of guideline-recommended treatments. Szummer et al. present in the current issue of the European Heart Journal an analysis of 20-year outcomes in 205 693 cases of non ST-elevation MI (NSTEMI) in SWEDEHEART. This required additional adjustments, accounting for the shift in biomarkers used to diagnose MI from creatine kinase (CK)-MB (89.6% in 1995–1996) to cardiac-specific troponins (99% in 2013–2014). Aspirin and betablockers were generally in broad use already in the mid-1990s, but ACEIs/ARBs, statins, PCI, coronary angiography, and dual antiplatelet therapy showed progressive dramatic increases in use over the 2-year blocks through 2013–2014. Tracking with the increases in use of recommended treatments were significant reductions in crude in-hospital and 1-year total and cardiovascular deaths. Standardized in-hospital and 1-year rates of death/MI also showed progressive significant declines over time. Additional analyses that support the association between greater use of guideline treatments and improvements in outcomes after NSTEMI include regression analyses adjusting for age and gender, baseline characteristics, and in-hospital angiography/PCI. Standardized incidence rate ratios compared with the general population showed that the risk of death was 5.5 times higher in NSTEMI patients in 1995–1996 and declined to 3.03 times higher in 2013–2014. What are we to make of these impressive findings? It is gratifying to see translation of the results of clinical trials into practice. While we cannot assign causation between the significant trends in increasing use of effective treatments and progressive improvement in outcomes, there is strong biological plausibility that treatments tracked in SWEDEHEART are in the causal pathway for improvements in outcome. Enhancing flow in compromised coronary arteries, maintaining patency with stents and combination antithrombotics, and unloading a damaged left ventricle with ACEI/ARB treatments have all been shown to reduce morbidity and mortality from an ACS event. Evidence supporting the treatments tracked in SWEDEHEART was

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Improving care at the population and individual level: lessons from SWEDEHEART.

Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs Neither of these paths is desirable for future development of therapeutics We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology) Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system

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Elliott M. Antman

Papers

Data from Digital Health Devices Informs Ideal Cardiovascular Health.

Abstract 1999: Angiographic and Clinical Outcomes Among Patients with Acute Coronary Syndrome Presenting with Isolated Anterior ST-Segment Depressions

Improving care at the population and individual level: lessons from SWEDEHEART.

Clinical Research and the Development of Medical Therapeutics

Discharge aspirin dose and clinical outcomes in patients with acs: an analysis from the triton-timi 38 study