This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

Implications and Generalizability of Randomized Trials

Cynthia D. Mulrow, MD, MSc; John A. Cornell, PhD; Carlos R. Herrera, MD, MPH; Abdulmajead Kadri, PharmD; Lisa Farnett, PharmD; Christine Aguilar, MD, MPH

JAMA. 1994;272(24):1932-1938.

Abstract
Objective.
—To estimate morbidity and mortality benefits of drug therapy for hypertensive elderly subjects, compare these benefits with effects in younger subjects, and provide a framework for generalizing results derived from trials to actual patients.

Data Sources.
—A literature search using MEDLINE from 1966 to 1993, references from reviews and trial articles, and experts.

Study Selection.
—Randomized trials lasting at least 1 year that evaluated effects of drug treatment on morbidity and mortality outcomes in hypertensive persons.

Data Extraction.
—Four independent reviewers appraised protocol characteristics and quality of selected trials.

Data Synthesis.
—There were 13 trials involving 16 564 elderly persons (age 60 years and older). The prevalence of cardiovascular risk factors, cardiovascular disease, and competing comorbid diseases was lower among trial participants than the general population of hypertensive elderly persons. When the six large high-quality trials were combined, trial results showed 43 subjects (95% confidence interval [CI], 31 to 69) and 61 subjects (95% CI, 39 to 141) needed to be treated for 5 years to prevent one cerebrovascular event and one coronary heart disease event, respectively. Including the other seven trials did not change the results significantly. Only 18 subjects (95% CI, 14 to 25) needed to be treated to prevent one cardiovascular event (cerebrovascular or cardiac). Twelve trials in primarily younger and middle-aged adults involved approximately 33 000 persons. For all outcomes except cardiac mortality, two to fourtimes as many of the younger subjects as the older subjects needed to be treated for 5 years to prevent morbid and mortal events. No significant effect on cardiac mortality was seen among younger subjects, while 78 older subjects (95% CI, 50 to 180) needed to be treated to prevent a fatal cardiac event.

Conclusions.
—Randomized trials demonstrate that treating healthy older persons with hypertension is highly efficacious. Five-year morbidity and mortality benefits derived from trials are greater for older than younger subjects. Extrapolating benefits from trials to individual patients is difficult, but should take into account multiple issues including the patient's risk factors, preexisting cardiovascular disease, and competing comorbid illnesses.

(JAMA. 1994;272:1932-1938)

Author Affiliations
From the Geriatric Research, Education and Clinical Center, the Audie L. Murphy Memorial Veterans Hospital, San Antonio, Tex (Drs Mulrow, Cornell, Kadri, and Farnett), and the University of Texas Health Science Centers at Houston (Dr Herrera) and San Antonio (Drs Mulrow, Cornell, and Aguilar). Dr Mulrow is a Veterans Affairs senior research associate. No financial support was received for this work.

Footnotes
Reprint requests to Audie L. Murphy Memorial Veterans Hospital, Ambulatory Care (11C6), 7400 Merton Minter Blvd, San Antonio, TX 78284 (Dr Mulrow),

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study
de Ruijter et al.
BMJ 2009;338:a3083-a3083.
ABSTRACT | FULL TEXT  

Impact of Salmeterol/Fluticasone Propionate versus Salmeterol on Exacerbations in Severe Chronic Obstructive Pulmonary Disease
Kardos et al.
Am. J. Respir. Crit. Care Med. 2007;175:144-149.
ABSTRACT | FULL TEXT  

Prevention of cardiovascular diseases: focus on modifiable cardiovascular risk
El Fakiri et al.
Heart 2006;92:741-745.
ABSTRACT | FULL TEXT  

Number needed to treat: A descriptor for weighing therapeutic options
Wen et al.
Am J Health Syst Pharm 2005;62:2031-2036.
ABSTRACT | FULL TEXT  

A 60-Year-Old Woman With Atrial Fibrillation
Singer
JAMA 2003;290:2182-2189.
FULL TEXT  

Is there a role for nurse-led blood pressure management in primary care?
Oakeshott et al.
Fam Pract 2003;20:469-473.
ABSTRACT | FULL TEXT  

Health Outcomes Associated With Various Antihypertensive Therapies Used as First-Line Agents: A Network Meta-analysis
Psaty et al.
JAMA 2003;289:2534-2544.
ABSTRACT | FULL TEXT  

The elderly hypertensive population: what lies ahead of us?
Bobrie and Potter
Journal of Renin-Angiotensin-Aldosterone System 2002;3:S4-S9.
 

Can we individualize the 'number needed to treat'? An empirical study of summary effect measures in meta-analyses
Furukawa et al.
Int J Epidemiol 2002;31:72-76.
ABSTRACT | FULL TEXT  

Assessment of absolute risk of death after myocardial infarction by use of multiple-risk-factor assessment equations; GISSI-Prevenzione mortality risk chart
Marchioli et al.
Eur Heart J 2001;22:2085-2103.
ABSTRACT  

Why do GPs not implement evidence-based guidelines? A descriptive study
Cranney et al.
Fam Pract 2001;18:359-363.
ABSTRACT | FULL TEXT  

Oral Arginine Improves Blood Pressure in Renal Transplant and Hemodialysis Patients
Kelly et al.
JPEN J Parenter Enteral Nutr 2001;25:194-202.
ABSTRACT  

The Use of Numbers Needed to Treat Derived from Systematic Reviews and Meta-Analysis: Caveats and Pitfalls
Ebrahim
Eval Health Prof 2001;24:152-164.
ABSTRACT  

Lowering blood pressure in particular patient groups
DTB 2001;39:37-40.
ABSTRACT | FULL TEXT  

Hypertension in Older Adults
Rigaud and Forette
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2001;56:217M-225.
ABSTRACT | FULL TEXT  

Benefits of Screening for Latent Mycobacterium tuberculosis Infection
Rose
Arch Intern Med 2000;160:1513-1521.
ABSTRACT | FULL TEXT  

Guidelines on preventing cardiovascular disease in clinical practice
Jackson
BMJ 2000;320:659-661.
FULL TEXT  

Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treated
Baker et al.
BMJ 2000;320:680-685.
ABSTRACT | FULL TEXT  

Updated New Zealand cardiovascular disease risk-benefit prediction guide
Jackson
BMJ 2000;320:709-710.
FULL TEXT  

Calcium Channel Blockers and Mortality in Elderly Patients With Myocardial Infarction
Jollis et al.
Arch Intern Med 1999;159:2341-2348.
ABSTRACT | FULL TEXT  

Hypertension in Men
August
J. Clin. Endocrinol. Metab. 1999;84:3451-3454.
FULL TEXT  

Cardiovascular health check in the elderly in one general practice: does it offer new information and lead to interventions?
van den Berg et al.
Fam Pract 1999;16:389-394.
ABSTRACT | FULL TEXT  

Systematic review of antihypertensive therapies: Does the evidence assist in choosing a first-line drug?
Wright et al.
CMAJ 1999;161:25-32.
ABSTRACT | FULL TEXT  

Numbers needed to treat derived from meta-analyses---sometimes informative, usually misleading
Smeeth et al.
BMJ 1999;318:1548-1551.
FULL TEXT  

Better by half: hypertension in the elderly and the ‘rule of halves’: a primary care audit of the clinical computer record as a springboard to improving care
Hooker et al.
Fam Pract 1999;16:123-128.
ABSTRACT | FULL TEXT  

Performance indicators for primary care groups
Myers et al.
BMJ 1999;318:803-803.
FULL TEXT  

Prevalence, Clinical Correlates, and Treatment of Hypertension in Elderly Nursing Home Residents
Gambassi et al.
Arch Intern Med 1998;158:2377-2385.
ABSTRACT | FULL TEXT  

Effect of Antihypertensive Treatment in Patients Having Already Suffered From Stroke : Gathering the Evidence
Gueyffier et al.
Stroke 1997;28:2557-2562.
ABSTRACT | FULL TEXT  

Heart Rate Adjustment of Exercise-Induced ST-Segment Depression Identifies Men Who Benefit From a Risk Factor Reduction Program
Okin et al.
Circulation 1997;96:2899-2904.
ABSTRACT | FULL TEXT  

Health Outcomes Associated With Antihypertensive Therapies Used as First-Line Agents: A Systematic Review and Meta-analysis
Psaty et al.
JAMA 1997;277:739-745.
ABSTRACT  

Hypertension and Borderline Isolated Systolic Hypertension Increase Risks of Cardiovascular Disease and Mortality in Male Physicians
O'Donnell et al.
Circulation 1997;95:1132-1137.
ABSTRACT | FULL TEXT  

Treating hypertension: the evidence from clinical trials
Simon
BMJ 1996;313:437-438.
FULL TEXT  

Guidelines for managing raised blood pressure
Jackson and Sackett
BMJ 1996;313:64-65.
FULL TEXT  

What constitutes controlled hypertension? Patient based comparison of hypertension guidelines
Fahey and Peters
BMJ 1996;313:93-96.
ABSTRACT | FULL TEXT  

Does Antihypertensive Treatment of the Elderly Prevent Cardiovascular Events or Prolong Life? A Meta-analysis of Hypertension Treatment Trials
Pearce et al.
Arch Fam Med 1995;4:943-949.
ABSTRACT  

Meta-Analytic Methods for Health Services Research: An Example from Geriatrics
Wieland et al.
Eval Health Prof 1995;18:252-282.
ABSTRACT  

Hypertension in the Elderly: Correction and Clarification
Borhani
JAMA 1995;274:25-25.
ABSTRACT  

Hypertension in the Elderly: Correction and Clarification
Hatch and Godbold
JAMA 1995;274:25-25.
ABSTRACT  

Thiazides and Hypertension in the Elderly
Gifford and Kaplan
Hypertension 1995;25:1052-1052.
FULL TEXT