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.

/pdf/cochrane-handbook-for-systematic-reviews-of-interventions-1xbdy6uvru.pdf

Cochrane Handbook for Systematic Reviews of Interventions

The T-Type calcium channel offers a new therapeutic target for teatment of patients with cardiovascular disease. Mibefradil, a T channel blocker, produces heart rate slowing and coronary vasodilatation but without the negative inotropic effect commonly seen when L-Type channel blockers are used. The present study shows Mibefradil prevents ischemic episodes that are and are not preceded by an increase in heart rate. Although Mibefradil has been withdrawn because of multiple drug interactions, new T-Type calcium channel blockers are under development.

T-type calcium channel blockade in the management of chronic ischemic heart disease.

Treatment of unstable coronary artery disease with a combination of aspirin and intravenous heparin is now widely established but carries a significant failure rate, the origins of which lie in the fundamental characteristics of heparin and aspirin. The use of low-molecular-weight heparins (LMWHs) as an alternative to unfractionated heparin carries theoretical and practical advantages. Clinical trial evidence is now available to show that the LMWH enoxaparin, in a dosage of 1.0 mg. kg -1 subcutaneously every 12 h for 2-8 days, is significantly more effective than unfractionated heparin, and that the benefits persist even after treatment ends. Ongoing trials will provide more efficacy data over both the short and the longer term. Enoxaparin at a dosage of 1.0 mg . kg -1 every 12 h is as effective as higher doses but is associated with a much lower rate of major haemorrhage.

Treatment options in unstable angina: a clinical update.

Abstract 2221: Triple Therapy (TTx): ASA, Thienopyridine and Oral Anticoagulation (OA) Therapy Following ST Elevation Myocardial Infarction (STEMI): Is it Safe?

Intensive antiplatelet therapy for reduction of ischaemic events – Authors' reply

[1] Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary athersclerotic plaques underlying fatal occlusive thrombi. Br Heart J 1983; 50: 127–34. [2] Davies MJ, Bland JM, Hangartner JR, Angelini A, Thomas AC . Factors influencing the presence or absence of acute coronary thrombi in sudden ischaemic death. Eur Heart J 1989; 10: 203–8. [3] Starry HD, Chandler AB, Dinsmore RE et al. A definition of advanced types of atherosclerotic lesions in the histological classification of atherosclerosis. Arterioscler Thromb Vasc Biol 1995; 15: 1512–31. [4] Virmini R, Kolodgie D, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262–75. [5] Burke AP, Kolodgie D, Farb A. et al. Healed plaque ruptures and sudden coronary death. Evidence that sub-clinical rupture has a role in plaque progression. Circulation 2001; 103: 934–40. [6] Farb A, Burke AP, Tang ,AL et al. Coronary plaque erosion without rupture in to a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93: 1354–63. [7] Burke AP, Farb A, Malcolm GT et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 336: 1276–82. [8] Leach IH, Blundell JW, Rowley JM, Turner DR.. Acute ischaemic lesions in death due to ischaemic heart disease: an autopsy study of 333 cases of out-of-hospital deaths. Eur Heart J 1995; 16: 1181–5. [9] Arbustini E, Dal Bello B, Morbinni P et al. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart 1999; 82: 269–72. [10] Henriques de Gouveia R, van der Wal AC, van der Loos CM, Becker AE. . Sudden unexpected death in young adults. Discrepancies between initiation of acute plaque complications and the onset of acute coronary death. Eur Heart J 2002; 23: 1433–1440.

Elliott M. Antman

Papers

T-type calcium channel blockade in the management of chronic ischemic heart disease.

Treatment options in unstable angina: a clinical update.

Abstract 2221: Triple Therapy (TTx): ASA, Thienopyridine and Oral Anticoagulation (OA) Therapy Following ST Elevation Myocardial Infarction (STEMI): Is it Safe?

Intensive antiplatelet therapy for reduction of ischaemic events – Authors' reply

‘I can see clearly now’: a new view on the use of IV GP IIb/IIIa inhibitors in acute coronary syndromes