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Does treatment with donepezil improve memory for patients with mild cognitive impairment?
Donepezil (Aricept) has potential benefit in delaying risk of progression to Alzheimer’s disease in the first year of treatment, but this benefit is not seen at 3 years. Donepezil does not improve memory for patients with mild cognitive impairment (strength of recommendation: B).
Donepezil’s cost, limited proven benefit, side effects argue against it as standard of care
Robert K. Persons, DO, FAAFP
Air Armament Center Family Medicine Residency, 96 Medical Group, Eglin Air Force Base, Eglin, Fla
The downward spiral of a patient with Alzheimer’s disease is heartbreaking, so any possibility of slowing this process is welcome. Many physicians, when challenged with the desire to assist the patient with mild cognitive impairment and their family, review the data showing that donepezil slows progression in Alzheimer’s disease, as well as briefly from mild cognitive impairment to Alzheimer’s disease. They discuss with the family the imprecise nature of diagnosis,1 risks vs benefits of therapy, and start an 8-week trial of therapy. If the family notes improvement (or stabilization), treatment can be continued. However, the cost of the medication, the limited proven benefit, and the side-effect profile argue against any clear standard of care.
Evidence summary
Mild cognitive impairment is defined as memory loss that is out of proportion to that expected for one’s age but which does not meet the clinical criteria for dementia. The diagnosis of dementia requires cognitive impairment plus functional impairment. In mild cognitive impairment, function is preserved by definition.
Several studies have shown that patients with mild cognitive impairment progress to Alzheimer’s disease at a higher rate than normal elderly patients.2,3 Research has focused on therapies that have shown a positive benefit for patients with Alzheimer’s disease.4,5 Cholinesterase inhibitors, including donepezil, have shown some benefit in cognition and function for patients with mild to moderate Alzheimer’s disease. Two randomized controlled trials (RCTs) address the effect of donepezil on mild cognitive impairment.
The National Institute of Aging conducted a double-blind RCT multicenter study, which enrolled a total of 769 subjects with mild cognitive impairment. The primary outcome was the development of possible or probable Alzheimer’s disease, and secondary outcomes included cognition and function. Subjects were randomly assigned to receive 2000 IU of vitamin E, 10 mg of donepezil, or placebo daily for 3 years. Of the total, 214 (28%) of the study subjects progressed to dementia, with 212 classified as possible or probable Alzheimer’s disease. Analysis of the treatment effects at 6-month intervals showed a decreased probability of progression to Alzheimer’s disease in the donepezil group during the first 12 months of the study, compared with placebo (14.7% vs 6.3%; P=.04; number needed to treat [NNT]=12), but this change did not persist to 3 years.
Several of the psychometric tests showed statistically significant differences (scores for Mini-Mental State Examination [MMSE], Clinical Dementia Rating [CDR] sum of boxes, Global Deterioration Scale, and modified Alzheimer’s disease Assessment Scale-cognitive subscale [ADAS-cog]) early in the study, but the effect was only detected in the first 12 months of the study.6,7 The donepezil group had significantly higher rates diarrhea, muscle cramps, insomnia, nausea, and abnormal dreams (P<.01). There was no difference in discontinuation rates between the groups.7
The second study was a 24-week multicenter RCT, which included 270 patients with amnestic mild cognitive impairment. Patients were randomized to receive placebo or donepezil (5 mg/d for 42 days, followed by 10 mg/d). The primary end-points were changes on the New York University Paragraph Delayed Recall test and the Alzheimer’s disease Cooperative Study Clinician’s Global Impression of Change for Mild Cognitive Impairment (ADCS CGIC-MCI). No significant differences were found in the primary endpoints at 24 weeks—32.6% in the donepezil group vs 24.3 % in the placebo group showed minimal or moderate improvement, and 51.7% in the donepezil group vs 60.4% in the placebo group showed no change. Secondary endpoints included the modified ADAS-cog, the Patient global Assessment (PGA) and other neuropsychological tests.
The ADAS-cog focuses on psychomotor speed and attention tests. Analysis of the ADAS-cog favored the donepezil group, with 22.3% showing a ≥7-point score vs 12.1% in the placebo group. There were no significant differences on the PGA in the intention-to-treat analysis.8 The donepezil group had a higher rate of adverse drug reactions (P<.03) including diarrhea, nausea, vomiting, leg cramps, and abnormal dreams. The discontinuation rate was 22% in the donepezil group compared with 8% in the placebo group (number needed to harm=7).8
Recommendations from others
We found no recommendations about using cholinesterase inhibitors in mild cognitive impairment.
1. Luis CA, Loewenstein DA, Acevedo A, Barker WW, Duara R. Mild cognitive impairment-Directions for future research. Neurology 2003;61:438-444.
2. Pinals SL, Santa Teresa MM. Early recognition, management, and treatment of mild cognitive impairment and its relationship to Alzheimer’s disease. Primary Psychiatry 2004;11:41-47.
3. Jelic V, Winblad B. Treatment of mild cognitive impairment: rationale, present and future strategies. Acta Neurol Scand 2003;107(Suppl 179):83-93.
4. Meyer JS, Li Y, Xu G, Thornby J, Chowdhury M, Quach M. Feasibility of treating mild cognitive impairment with cholinesterase inhibitors. Int J Geriatr Psychiatry 2002;17:586-588.
5. Sramek JJ, Veroff AE, Cutler NR. The status of ongoing trials for mild cognitive impairment. Exp Opin Invest Drugs 2001;10:741-752.
6. Grundman M, Petersen RC, Ferris SH, et al. Mild cognitive impairment can be distinguished from Alzheimer Disease and normal aging for clinical trials. Arch Neurol 2004;61:59-66.
7. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and Donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;352:2379-2388.
8. Salloway S, Ferris S, Kluger A, et al. Efficacy of donepezil in mild cognitive impairment: A randomized placebo-controlled trial. Neurology 2004;63:651-657.
Donepezil (Aricept) has potential benefit in delaying risk of progression to Alzheimer’s disease in the first year of treatment, but this benefit is not seen at 3 years. Donepezil does not improve memory for patients with mild cognitive impairment (strength of recommendation: B).
Donepezil’s cost, limited proven benefit, side effects argue against it as standard of care
Robert K. Persons, DO, FAAFP
Air Armament Center Family Medicine Residency, 96 Medical Group, Eglin Air Force Base, Eglin, Fla
The downward spiral of a patient with Alzheimer’s disease is heartbreaking, so any possibility of slowing this process is welcome. Many physicians, when challenged with the desire to assist the patient with mild cognitive impairment and their family, review the data showing that donepezil slows progression in Alzheimer’s disease, as well as briefly from mild cognitive impairment to Alzheimer’s disease. They discuss with the family the imprecise nature of diagnosis,1 risks vs benefits of therapy, and start an 8-week trial of therapy. If the family notes improvement (or stabilization), treatment can be continued. However, the cost of the medication, the limited proven benefit, and the side-effect profile argue against any clear standard of care.
Evidence summary
Mild cognitive impairment is defined as memory loss that is out of proportion to that expected for one’s age but which does not meet the clinical criteria for dementia. The diagnosis of dementia requires cognitive impairment plus functional impairment. In mild cognitive impairment, function is preserved by definition.
Several studies have shown that patients with mild cognitive impairment progress to Alzheimer’s disease at a higher rate than normal elderly patients.2,3 Research has focused on therapies that have shown a positive benefit for patients with Alzheimer’s disease.4,5 Cholinesterase inhibitors, including donepezil, have shown some benefit in cognition and function for patients with mild to moderate Alzheimer’s disease. Two randomized controlled trials (RCTs) address the effect of donepezil on mild cognitive impairment.
The National Institute of Aging conducted a double-blind RCT multicenter study, which enrolled a total of 769 subjects with mild cognitive impairment. The primary outcome was the development of possible or probable Alzheimer’s disease, and secondary outcomes included cognition and function. Subjects were randomly assigned to receive 2000 IU of vitamin E, 10 mg of donepezil, or placebo daily for 3 years. Of the total, 214 (28%) of the study subjects progressed to dementia, with 212 classified as possible or probable Alzheimer’s disease. Analysis of the treatment effects at 6-month intervals showed a decreased probability of progression to Alzheimer’s disease in the donepezil group during the first 12 months of the study, compared with placebo (14.7% vs 6.3%; P=.04; number needed to treat [NNT]=12), but this change did not persist to 3 years.
Several of the psychometric tests showed statistically significant differences (scores for Mini-Mental State Examination [MMSE], Clinical Dementia Rating [CDR] sum of boxes, Global Deterioration Scale, and modified Alzheimer’s disease Assessment Scale-cognitive subscale [ADAS-cog]) early in the study, but the effect was only detected in the first 12 months of the study.6,7 The donepezil group had significantly higher rates diarrhea, muscle cramps, insomnia, nausea, and abnormal dreams (P<.01). There was no difference in discontinuation rates between the groups.7
The second study was a 24-week multicenter RCT, which included 270 patients with amnestic mild cognitive impairment. Patients were randomized to receive placebo or donepezil (5 mg/d for 42 days, followed by 10 mg/d). The primary end-points were changes on the New York University Paragraph Delayed Recall test and the Alzheimer’s disease Cooperative Study Clinician’s Global Impression of Change for Mild Cognitive Impairment (ADCS CGIC-MCI). No significant differences were found in the primary endpoints at 24 weeks—32.6% in the donepezil group vs 24.3 % in the placebo group showed minimal or moderate improvement, and 51.7% in the donepezil group vs 60.4% in the placebo group showed no change. Secondary endpoints included the modified ADAS-cog, the Patient global Assessment (PGA) and other neuropsychological tests.
The ADAS-cog focuses on psychomotor speed and attention tests. Analysis of the ADAS-cog favored the donepezil group, with 22.3% showing a ≥7-point score vs 12.1% in the placebo group. There were no significant differences on the PGA in the intention-to-treat analysis.8 The donepezil group had a higher rate of adverse drug reactions (P<.03) including diarrhea, nausea, vomiting, leg cramps, and abnormal dreams. The discontinuation rate was 22% in the donepezil group compared with 8% in the placebo group (number needed to harm=7).8
Recommendations from others
We found no recommendations about using cholinesterase inhibitors in mild cognitive impairment.
Donepezil (Aricept) has potential benefit in delaying risk of progression to Alzheimer’s disease in the first year of treatment, but this benefit is not seen at 3 years. Donepezil does not improve memory for patients with mild cognitive impairment (strength of recommendation: B).
Donepezil’s cost, limited proven benefit, side effects argue against it as standard of care
Robert K. Persons, DO, FAAFP
Air Armament Center Family Medicine Residency, 96 Medical Group, Eglin Air Force Base, Eglin, Fla
The downward spiral of a patient with Alzheimer’s disease is heartbreaking, so any possibility of slowing this process is welcome. Many physicians, when challenged with the desire to assist the patient with mild cognitive impairment and their family, review the data showing that donepezil slows progression in Alzheimer’s disease, as well as briefly from mild cognitive impairment to Alzheimer’s disease. They discuss with the family the imprecise nature of diagnosis,1 risks vs benefits of therapy, and start an 8-week trial of therapy. If the family notes improvement (or stabilization), treatment can be continued. However, the cost of the medication, the limited proven benefit, and the side-effect profile argue against any clear standard of care.
Evidence summary
Mild cognitive impairment is defined as memory loss that is out of proportion to that expected for one’s age but which does not meet the clinical criteria for dementia. The diagnosis of dementia requires cognitive impairment plus functional impairment. In mild cognitive impairment, function is preserved by definition.
Several studies have shown that patients with mild cognitive impairment progress to Alzheimer’s disease at a higher rate than normal elderly patients.2,3 Research has focused on therapies that have shown a positive benefit for patients with Alzheimer’s disease.4,5 Cholinesterase inhibitors, including donepezil, have shown some benefit in cognition and function for patients with mild to moderate Alzheimer’s disease. Two randomized controlled trials (RCTs) address the effect of donepezil on mild cognitive impairment.
The National Institute of Aging conducted a double-blind RCT multicenter study, which enrolled a total of 769 subjects with mild cognitive impairment. The primary outcome was the development of possible or probable Alzheimer’s disease, and secondary outcomes included cognition and function. Subjects were randomly assigned to receive 2000 IU of vitamin E, 10 mg of donepezil, or placebo daily for 3 years. Of the total, 214 (28%) of the study subjects progressed to dementia, with 212 classified as possible or probable Alzheimer’s disease. Analysis of the treatment effects at 6-month intervals showed a decreased probability of progression to Alzheimer’s disease in the donepezil group during the first 12 months of the study, compared with placebo (14.7% vs 6.3%; P=.04; number needed to treat [NNT]=12), but this change did not persist to 3 years.
Several of the psychometric tests showed statistically significant differences (scores for Mini-Mental State Examination [MMSE], Clinical Dementia Rating [CDR] sum of boxes, Global Deterioration Scale, and modified Alzheimer’s disease Assessment Scale-cognitive subscale [ADAS-cog]) early in the study, but the effect was only detected in the first 12 months of the study.6,7 The donepezil group had significantly higher rates diarrhea, muscle cramps, insomnia, nausea, and abnormal dreams (P<.01). There was no difference in discontinuation rates between the groups.7
The second study was a 24-week multicenter RCT, which included 270 patients with amnestic mild cognitive impairment. Patients were randomized to receive placebo or donepezil (5 mg/d for 42 days, followed by 10 mg/d). The primary end-points were changes on the New York University Paragraph Delayed Recall test and the Alzheimer’s disease Cooperative Study Clinician’s Global Impression of Change for Mild Cognitive Impairment (ADCS CGIC-MCI). No significant differences were found in the primary endpoints at 24 weeks—32.6% in the donepezil group vs 24.3 % in the placebo group showed minimal or moderate improvement, and 51.7% in the donepezil group vs 60.4% in the placebo group showed no change. Secondary endpoints included the modified ADAS-cog, the Patient global Assessment (PGA) and other neuropsychological tests.
The ADAS-cog focuses on psychomotor speed and attention tests. Analysis of the ADAS-cog favored the donepezil group, with 22.3% showing a ≥7-point score vs 12.1% in the placebo group. There were no significant differences on the PGA in the intention-to-treat analysis.8 The donepezil group had a higher rate of adverse drug reactions (P<.03) including diarrhea, nausea, vomiting, leg cramps, and abnormal dreams. The discontinuation rate was 22% in the donepezil group compared with 8% in the placebo group (number needed to harm=7).8
Recommendations from others
We found no recommendations about using cholinesterase inhibitors in mild cognitive impairment.
1. Luis CA, Loewenstein DA, Acevedo A, Barker WW, Duara R. Mild cognitive impairment-Directions for future research. Neurology 2003;61:438-444.
2. Pinals SL, Santa Teresa MM. Early recognition, management, and treatment of mild cognitive impairment and its relationship to Alzheimer’s disease. Primary Psychiatry 2004;11:41-47.
3. Jelic V, Winblad B. Treatment of mild cognitive impairment: rationale, present and future strategies. Acta Neurol Scand 2003;107(Suppl 179):83-93.
4. Meyer JS, Li Y, Xu G, Thornby J, Chowdhury M, Quach M. Feasibility of treating mild cognitive impairment with cholinesterase inhibitors. Int J Geriatr Psychiatry 2002;17:586-588.
5. Sramek JJ, Veroff AE, Cutler NR. The status of ongoing trials for mild cognitive impairment. Exp Opin Invest Drugs 2001;10:741-752.
6. Grundman M, Petersen RC, Ferris SH, et al. Mild cognitive impairment can be distinguished from Alzheimer Disease and normal aging for clinical trials. Arch Neurol 2004;61:59-66.
7. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and Donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;352:2379-2388.
8. Salloway S, Ferris S, Kluger A, et al. Efficacy of donepezil in mild cognitive impairment: A randomized placebo-controlled trial. Neurology 2004;63:651-657.
1. Luis CA, Loewenstein DA, Acevedo A, Barker WW, Duara R. Mild cognitive impairment-Directions for future research. Neurology 2003;61:438-444.
2. Pinals SL, Santa Teresa MM. Early recognition, management, and treatment of mild cognitive impairment and its relationship to Alzheimer’s disease. Primary Psychiatry 2004;11:41-47.
3. Jelic V, Winblad B. Treatment of mild cognitive impairment: rationale, present and future strategies. Acta Neurol Scand 2003;107(Suppl 179):83-93.
4. Meyer JS, Li Y, Xu G, Thornby J, Chowdhury M, Quach M. Feasibility of treating mild cognitive impairment with cholinesterase inhibitors. Int J Geriatr Psychiatry 2002;17:586-588.
5. Sramek JJ, Veroff AE, Cutler NR. The status of ongoing trials for mild cognitive impairment. Exp Opin Invest Drugs 2001;10:741-752.
6. Grundman M, Petersen RC, Ferris SH, et al. Mild cognitive impairment can be distinguished from Alzheimer Disease and normal aging for clinical trials. Arch Neurol 2004;61:59-66.
7. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and Donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;352:2379-2388.
8. Salloway S, Ferris S, Kluger A, et al. Efficacy of donepezil in mild cognitive impairment: A randomized placebo-controlled trial. Neurology 2004;63:651-657.
Evidence-based answers from the Family Physicians Inquiries Network
How reliable are self-measured blood pressures taken at home?
Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations (strength of recommendation [SOR]: B, extrapolation and limited trials). Clinicians using SMBP need to be aware of the difference in normal reference ranges, with pressures greater than 135/85 mm Hg considered hypertensive.
Whether hypertensive treatment should be based primarily on SMBP is unclear, and currently undergoing study. Clinicians should recommend multiple daily measurements with a validated and standardized device, preferably equipped with memory or transmission capabilities, in order to avoid patient error in transcribing and reporting values. Wrist or finger devices cannot reliably be used (SOR: B, limited comparison studies).
Evidence summary
Office blood pressure (OBP) has traditionally been used in long-term trials to describe the relationship between blood pressure and cardiovascular morbidity and mortality, as well as to establish the efficacy of antihypertensive drug therapy. A prospective randomized trial demonstrating the relationship between therapy based on SMBP to these same outcomes is in progress.1
Two large prospective cohort studies of the relationship between SMBP and morbidity and mortality made comparative baseline blood pressure measurements and followed the cohorts without suggestions or attempts to change management. The first was a rural population-based study with 1789 subjects (90% of the population) from Ohasama, Japan.2 Mean follow-up was 6.6 years with less than 1% dropout rate. The second large cohort study (SHEAF trial) included patients 60 years old with the diagnosis of hypertension.3 A total of 4939 cases were analyzed. Mean follow-up was 3.2 years with less than 1% dropout rate. Both studies show that each mm Hg increase in SMBP was a better predictor of cardiovascular events than an equivalent increase in OBP (Table 1).
Office blood pressure measurements exhibit large variability (decreased precision) and are subject to multiple biases (decreased accuracy). Self-measured blood pressures at home became common when “white-coat hypertension” was recognized to be clinically significant. It allows for a larger number of measurements for individual patients, resulting in greater precision than OBP.4 SMBP correlates better than OBP with surrogate measures of hypertensive control, such as ambulatory blood pressure measurement5 and left ventricular mass.6 Thus, SMBP might some day become the gold standard for defining hypertension in the clinical setting. Meanwhile, the correlation between OBP and SMBP can be derived via three different mathematical models using data from multiple studies. The accepted cutoff for SMBP defined hypertension is 135/85 mm Hg.7
The THOP trial8 was a single-blinded, randomized controlled trial of hypertensive treatment based on SMBP vs OBP. Four hundred patients were randomized to SMBP or OBP, with medication adjustments made by a blinded clinician. The trial design called for both treatment groups to be titrated to a diastolic blood pressure of 80 to 89 mm Hg. The follow-up was approximately 1 year. Graphical data indicate that both groups were equally effective in meeting the blood pressure goals outlined in the methods.
Other differences in outcomes were proportional to the known difference in normotensive reference ranges (eg, that OBP tend to run higher than SMBP). Patients in the SMBP group were put on less-intensive drug treatment and incurred slightly lower medical costs. SMBP patients were twice as likely to have their blood pressure medication discontinued, possibly indicating SMBP helped to identify white-coat hypertension.
TABLE 1
Increase in cardiovascular mortality for each 1 mm Hg increase in blood pressure
| Cox Proportional Relative Hazards Ratio [95 % CI] | ||||
|---|---|---|---|---|
| Home systolic BP | Home diastolic BP | Office systolic BP | Office diastolic BP | |
| Ohasama study2* | 1.021[1.001–1.041]‡ | 1.015 [0.986–1.045] | 1.005 [0.990–1.020] | 1.008 [0.984–1.033] |
| SHEAF study3† | 1.02 [1.01–1.02]‡ | 1.02 [1.01–1.03]‡ | 1.01 [1.00–1.01] | 1.00 [0.99–1.02] |
| *Results were adjusted for age, sex, smoking status, history of cardiovascular disease, and use of antihypertensive medication. | ||||
| †Increase in cardiovascular events for each 1 mm Hg increase in blood pressure. Results were adjusted for age, sex, heart rate, smoking status, history of cardiovascular events, presence of diabetes, presence of obesity, and presence of treatment for hypercholesterolemia. | ||||
| ‡Statistically significant. | ||||
Recommendations from others
In addition to diagnosing white-coat hypertension, World Health Organization/International Society of Hypertension Guidelines Committee has recommended that home blood pressure measurement is useful in the following circumstances:9
- unusual variability of blood pressure over the same or different visits
- office hypertension in subjects with low cardiovascular risk
- symptoms suggesting hypotensive episodes
- hypertension resistant to drug treatment.
Standardization and validation protocols are available from the Association for the Advancement of Medical Instrumentation,10 European Hypertension Society,11 or the British Hypertension Society (available at www.hyp.ac.uk/bhs/bp_ monitors/automatic.htm). Relatively few of the hundreds of available blood pressure measurement devices available meet these criteria. The most current Association for the Advancement of Medical Instrumentation standards are labeled as ANSI/AAMI-SP10:2002/A1:2003 standards. Table 2 lists some devices that meet the various protocols. Devices in this market change rapidly, so buyers should confirm the device they are evaluating meets current standards.
TABLE 2
Devices that meet standards for home BP measurement
| SMBP device suitable for home use | Validation protocol |
|---|---|
| A&D-767 | BHS |
| A&D-779 | International Protocol |
| A&D-787 | International Protocol |
| OMRON M5-I | International Protocol |
| OMRON 705IT | International Protocol |
| OMRON 705 CPII | International Protocol |
| OMRON MIT | BHS |
| Microlife 3BTO-A | BHS |
| Microlife 3AG1 | BHS |
| BHS: British Hypertension Society; International Protocol: European Hypertension Society | |
Self-measured BP may help us better diagnose and manage hypertension
Paul Pisarik, MD, MPH
Baylor College of Medicine, Houston, Tex
It has been shown that office blood pressure readings can give false-positive results in those who have “white coat hypertension” and give false-negative readings in those with “white coat normotension” or “masked hypertension”—patients who have normal blood pressure values in the office, but elevated blood pressure values outside the office. This is not a trivial issue. Ten to 20% of patients with normal blood pressure values in the office have elevated blood pressure values throughout the day, and evidence is beginning to mount that the cardiovascular consequences are the same for these patients as for those with sustained hypertension.1
The SHEAF trial (and other studies) have thrown another complexity into hypertension control by showing that OBP readings were inaccurate in 22% of treated hypertensive patients—13% had uncontrolled OBP with normal SMBP, and 9% had normal OBP but uncontrolled SMBP.3
Thus, SMBP is a potentially very powerful and cost-effective tool that may help us better diagnose and manage this complex disease. I have encouraged my hypertensive patients to do SMBP and, as one who has white-coat hypertension (and a strong family history of hypertension), I am diligent at taking my own SMBP on a regular basis to guard against the insidious onset of this disease.
1. Fujiwara T, Matsubara M, Ohkubo T, Imai Y. Study Design of HOMED-BP: hypertension objective treatment based on measurement by electrical devices of blood pressure. Clin Exp Hypertens 2003;25:143-144.
2. Ohkubo T, Imai Y, Tsuji I, et al. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens 1998;16:971-975.
3. Bobrie G, Chatellier G, Genes N, et al. Cardiovascular prognosis of “masked hypertension” detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA 2004;291:1342-1349.
4. National Institutes of Health, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, MD: Public Health Service, NHLBI. NIH Publ. #03-5233, May 2003.
5. Brueren MM, Schouten JF, de Leeuw PW, van Montfrano GA, van Ree JW. A series of self-measurements by the patient is a reliable alternative to ambulatory blood pressure measurement. Br J Gen Pract 1998;48:1585-1589.
6. Verdecchia P. Reliability of home self-recorded arterial pressure in essential hypertension in relation to the stage of the disease. In: Ediziono GG (ed): Blood Pressure Recording in the Clinical Management of Hypertension. Rome: Pozzi; 1985;pp 40-42.
7. Thijs L, Staessen JA, Celis H, et al. Reference values for self-recorded blood pressure: a meta-analysis of summary data. Arch Intern Med 1998;158:481-488.
8. Staessen JA, Den Hond E, Celis H, et al. Antihypertensive treatment based on blood pressure measurement at home or in the physician’s office: a randomized controlled trial. JAMA 2004;291:955-964.
9. 1999 World Health Organization.International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 1999;17:151-185.
10. White WB, Berson AS, Robbins C, et al. National standard for measurement of resting and ambulatory pressures with automated sphygmomanometers. Hypertension 1993;21:504-509.
11. O’Brien E, Waeber B, Parati G, Staessen J, Myers MG. Blood pressure measuring devices: recommendations of the European Society of Hypertension. BMJ 2001;322:531-536.
Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations (strength of recommendation [SOR]: B, extrapolation and limited trials). Clinicians using SMBP need to be aware of the difference in normal reference ranges, with pressures greater than 135/85 mm Hg considered hypertensive.
Whether hypertensive treatment should be based primarily on SMBP is unclear, and currently undergoing study. Clinicians should recommend multiple daily measurements with a validated and standardized device, preferably equipped with memory or transmission capabilities, in order to avoid patient error in transcribing and reporting values. Wrist or finger devices cannot reliably be used (SOR: B, limited comparison studies).
Evidence summary
Office blood pressure (OBP) has traditionally been used in long-term trials to describe the relationship between blood pressure and cardiovascular morbidity and mortality, as well as to establish the efficacy of antihypertensive drug therapy. A prospective randomized trial demonstrating the relationship between therapy based on SMBP to these same outcomes is in progress.1
Two large prospective cohort studies of the relationship between SMBP and morbidity and mortality made comparative baseline blood pressure measurements and followed the cohorts without suggestions or attempts to change management. The first was a rural population-based study with 1789 subjects (90% of the population) from Ohasama, Japan.2 Mean follow-up was 6.6 years with less than 1% dropout rate. The second large cohort study (SHEAF trial) included patients 60 years old with the diagnosis of hypertension.3 A total of 4939 cases were analyzed. Mean follow-up was 3.2 years with less than 1% dropout rate. Both studies show that each mm Hg increase in SMBP was a better predictor of cardiovascular events than an equivalent increase in OBP (Table 1).
Office blood pressure measurements exhibit large variability (decreased precision) and are subject to multiple biases (decreased accuracy). Self-measured blood pressures at home became common when “white-coat hypertension” was recognized to be clinically significant. It allows for a larger number of measurements for individual patients, resulting in greater precision than OBP.4 SMBP correlates better than OBP with surrogate measures of hypertensive control, such as ambulatory blood pressure measurement5 and left ventricular mass.6 Thus, SMBP might some day become the gold standard for defining hypertension in the clinical setting. Meanwhile, the correlation between OBP and SMBP can be derived via three different mathematical models using data from multiple studies. The accepted cutoff for SMBP defined hypertension is 135/85 mm Hg.7
The THOP trial8 was a single-blinded, randomized controlled trial of hypertensive treatment based on SMBP vs OBP. Four hundred patients were randomized to SMBP or OBP, with medication adjustments made by a blinded clinician. The trial design called for both treatment groups to be titrated to a diastolic blood pressure of 80 to 89 mm Hg. The follow-up was approximately 1 year. Graphical data indicate that both groups were equally effective in meeting the blood pressure goals outlined in the methods.
Other differences in outcomes were proportional to the known difference in normotensive reference ranges (eg, that OBP tend to run higher than SMBP). Patients in the SMBP group were put on less-intensive drug treatment and incurred slightly lower medical costs. SMBP patients were twice as likely to have their blood pressure medication discontinued, possibly indicating SMBP helped to identify white-coat hypertension.
TABLE 1
Increase in cardiovascular mortality for each 1 mm Hg increase in blood pressure
| Cox Proportional Relative Hazards Ratio [95 % CI] | ||||
|---|---|---|---|---|
| Home systolic BP | Home diastolic BP | Office systolic BP | Office diastolic BP | |
| Ohasama study2* | 1.021[1.001–1.041]‡ | 1.015 [0.986–1.045] | 1.005 [0.990–1.020] | 1.008 [0.984–1.033] |
| SHEAF study3† | 1.02 [1.01–1.02]‡ | 1.02 [1.01–1.03]‡ | 1.01 [1.00–1.01] | 1.00 [0.99–1.02] |
| *Results were adjusted for age, sex, smoking status, history of cardiovascular disease, and use of antihypertensive medication. | ||||
| †Increase in cardiovascular events for each 1 mm Hg increase in blood pressure. Results were adjusted for age, sex, heart rate, smoking status, history of cardiovascular events, presence of diabetes, presence of obesity, and presence of treatment for hypercholesterolemia. | ||||
| ‡Statistically significant. | ||||
Recommendations from others
In addition to diagnosing white-coat hypertension, World Health Organization/International Society of Hypertension Guidelines Committee has recommended that home blood pressure measurement is useful in the following circumstances:9
- unusual variability of blood pressure over the same or different visits
- office hypertension in subjects with low cardiovascular risk
- symptoms suggesting hypotensive episodes
- hypertension resistant to drug treatment.
Standardization and validation protocols are available from the Association for the Advancement of Medical Instrumentation,10 European Hypertension Society,11 or the British Hypertension Society (available at www.hyp.ac.uk/bhs/bp_ monitors/automatic.htm). Relatively few of the hundreds of available blood pressure measurement devices available meet these criteria. The most current Association for the Advancement of Medical Instrumentation standards are labeled as ANSI/AAMI-SP10:2002/A1:2003 standards. Table 2 lists some devices that meet the various protocols. Devices in this market change rapidly, so buyers should confirm the device they are evaluating meets current standards.
TABLE 2
Devices that meet standards for home BP measurement
| SMBP device suitable for home use | Validation protocol |
|---|---|
| A&D-767 | BHS |
| A&D-779 | International Protocol |
| A&D-787 | International Protocol |
| OMRON M5-I | International Protocol |
| OMRON 705IT | International Protocol |
| OMRON 705 CPII | International Protocol |
| OMRON MIT | BHS |
| Microlife 3BTO-A | BHS |
| Microlife 3AG1 | BHS |
| BHS: British Hypertension Society; International Protocol: European Hypertension Society | |
Self-measured BP may help us better diagnose and manage hypertension
Paul Pisarik, MD, MPH
Baylor College of Medicine, Houston, Tex
It has been shown that office blood pressure readings can give false-positive results in those who have “white coat hypertension” and give false-negative readings in those with “white coat normotension” or “masked hypertension”—patients who have normal blood pressure values in the office, but elevated blood pressure values outside the office. This is not a trivial issue. Ten to 20% of patients with normal blood pressure values in the office have elevated blood pressure values throughout the day, and evidence is beginning to mount that the cardiovascular consequences are the same for these patients as for those with sustained hypertension.1
The SHEAF trial (and other studies) have thrown another complexity into hypertension control by showing that OBP readings were inaccurate in 22% of treated hypertensive patients—13% had uncontrolled OBP with normal SMBP, and 9% had normal OBP but uncontrolled SMBP.3
Thus, SMBP is a potentially very powerful and cost-effective tool that may help us better diagnose and manage this complex disease. I have encouraged my hypertensive patients to do SMBP and, as one who has white-coat hypertension (and a strong family history of hypertension), I am diligent at taking my own SMBP on a regular basis to guard against the insidious onset of this disease.
Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations (strength of recommendation [SOR]: B, extrapolation and limited trials). Clinicians using SMBP need to be aware of the difference in normal reference ranges, with pressures greater than 135/85 mm Hg considered hypertensive.
Whether hypertensive treatment should be based primarily on SMBP is unclear, and currently undergoing study. Clinicians should recommend multiple daily measurements with a validated and standardized device, preferably equipped with memory or transmission capabilities, in order to avoid patient error in transcribing and reporting values. Wrist or finger devices cannot reliably be used (SOR: B, limited comparison studies).
Evidence summary
Office blood pressure (OBP) has traditionally been used in long-term trials to describe the relationship between blood pressure and cardiovascular morbidity and mortality, as well as to establish the efficacy of antihypertensive drug therapy. A prospective randomized trial demonstrating the relationship between therapy based on SMBP to these same outcomes is in progress.1
Two large prospective cohort studies of the relationship between SMBP and morbidity and mortality made comparative baseline blood pressure measurements and followed the cohorts without suggestions or attempts to change management. The first was a rural population-based study with 1789 subjects (90% of the population) from Ohasama, Japan.2 Mean follow-up was 6.6 years with less than 1% dropout rate. The second large cohort study (SHEAF trial) included patients 60 years old with the diagnosis of hypertension.3 A total of 4939 cases were analyzed. Mean follow-up was 3.2 years with less than 1% dropout rate. Both studies show that each mm Hg increase in SMBP was a better predictor of cardiovascular events than an equivalent increase in OBP (Table 1).
Office blood pressure measurements exhibit large variability (decreased precision) and are subject to multiple biases (decreased accuracy). Self-measured blood pressures at home became common when “white-coat hypertension” was recognized to be clinically significant. It allows for a larger number of measurements for individual patients, resulting in greater precision than OBP.4 SMBP correlates better than OBP with surrogate measures of hypertensive control, such as ambulatory blood pressure measurement5 and left ventricular mass.6 Thus, SMBP might some day become the gold standard for defining hypertension in the clinical setting. Meanwhile, the correlation between OBP and SMBP can be derived via three different mathematical models using data from multiple studies. The accepted cutoff for SMBP defined hypertension is 135/85 mm Hg.7
The THOP trial8 was a single-blinded, randomized controlled trial of hypertensive treatment based on SMBP vs OBP. Four hundred patients were randomized to SMBP or OBP, with medication adjustments made by a blinded clinician. The trial design called for both treatment groups to be titrated to a diastolic blood pressure of 80 to 89 mm Hg. The follow-up was approximately 1 year. Graphical data indicate that both groups were equally effective in meeting the blood pressure goals outlined in the methods.
Other differences in outcomes were proportional to the known difference in normotensive reference ranges (eg, that OBP tend to run higher than SMBP). Patients in the SMBP group were put on less-intensive drug treatment and incurred slightly lower medical costs. SMBP patients were twice as likely to have their blood pressure medication discontinued, possibly indicating SMBP helped to identify white-coat hypertension.
TABLE 1
Increase in cardiovascular mortality for each 1 mm Hg increase in blood pressure
| Cox Proportional Relative Hazards Ratio [95 % CI] | ||||
|---|---|---|---|---|
| Home systolic BP | Home diastolic BP | Office systolic BP | Office diastolic BP | |
| Ohasama study2* | 1.021[1.001–1.041]‡ | 1.015 [0.986–1.045] | 1.005 [0.990–1.020] | 1.008 [0.984–1.033] |
| SHEAF study3† | 1.02 [1.01–1.02]‡ | 1.02 [1.01–1.03]‡ | 1.01 [1.00–1.01] | 1.00 [0.99–1.02] |
| *Results were adjusted for age, sex, smoking status, history of cardiovascular disease, and use of antihypertensive medication. | ||||
| †Increase in cardiovascular events for each 1 mm Hg increase in blood pressure. Results were adjusted for age, sex, heart rate, smoking status, history of cardiovascular events, presence of diabetes, presence of obesity, and presence of treatment for hypercholesterolemia. | ||||
| ‡Statistically significant. | ||||
Recommendations from others
In addition to diagnosing white-coat hypertension, World Health Organization/International Society of Hypertension Guidelines Committee has recommended that home blood pressure measurement is useful in the following circumstances:9
- unusual variability of blood pressure over the same or different visits
- office hypertension in subjects with low cardiovascular risk
- symptoms suggesting hypotensive episodes
- hypertension resistant to drug treatment.
Standardization and validation protocols are available from the Association for the Advancement of Medical Instrumentation,10 European Hypertension Society,11 or the British Hypertension Society (available at www.hyp.ac.uk/bhs/bp_ monitors/automatic.htm). Relatively few of the hundreds of available blood pressure measurement devices available meet these criteria. The most current Association for the Advancement of Medical Instrumentation standards are labeled as ANSI/AAMI-SP10:2002/A1:2003 standards. Table 2 lists some devices that meet the various protocols. Devices in this market change rapidly, so buyers should confirm the device they are evaluating meets current standards.
TABLE 2
Devices that meet standards for home BP measurement
| SMBP device suitable for home use | Validation protocol |
|---|---|
| A&D-767 | BHS |
| A&D-779 | International Protocol |
| A&D-787 | International Protocol |
| OMRON M5-I | International Protocol |
| OMRON 705IT | International Protocol |
| OMRON 705 CPII | International Protocol |
| OMRON MIT | BHS |
| Microlife 3BTO-A | BHS |
| Microlife 3AG1 | BHS |
| BHS: British Hypertension Society; International Protocol: European Hypertension Society | |
Self-measured BP may help us better diagnose and manage hypertension
Paul Pisarik, MD, MPH
Baylor College of Medicine, Houston, Tex
It has been shown that office blood pressure readings can give false-positive results in those who have “white coat hypertension” and give false-negative readings in those with “white coat normotension” or “masked hypertension”—patients who have normal blood pressure values in the office, but elevated blood pressure values outside the office. This is not a trivial issue. Ten to 20% of patients with normal blood pressure values in the office have elevated blood pressure values throughout the day, and evidence is beginning to mount that the cardiovascular consequences are the same for these patients as for those with sustained hypertension.1
The SHEAF trial (and other studies) have thrown another complexity into hypertension control by showing that OBP readings were inaccurate in 22% of treated hypertensive patients—13% had uncontrolled OBP with normal SMBP, and 9% had normal OBP but uncontrolled SMBP.3
Thus, SMBP is a potentially very powerful and cost-effective tool that may help us better diagnose and manage this complex disease. I have encouraged my hypertensive patients to do SMBP and, as one who has white-coat hypertension (and a strong family history of hypertension), I am diligent at taking my own SMBP on a regular basis to guard against the insidious onset of this disease.
1. Fujiwara T, Matsubara M, Ohkubo T, Imai Y. Study Design of HOMED-BP: hypertension objective treatment based on measurement by electrical devices of blood pressure. Clin Exp Hypertens 2003;25:143-144.
2. Ohkubo T, Imai Y, Tsuji I, et al. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens 1998;16:971-975.
3. Bobrie G, Chatellier G, Genes N, et al. Cardiovascular prognosis of “masked hypertension” detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA 2004;291:1342-1349.
4. National Institutes of Health, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, MD: Public Health Service, NHLBI. NIH Publ. #03-5233, May 2003.
5. Brueren MM, Schouten JF, de Leeuw PW, van Montfrano GA, van Ree JW. A series of self-measurements by the patient is a reliable alternative to ambulatory blood pressure measurement. Br J Gen Pract 1998;48:1585-1589.
6. Verdecchia P. Reliability of home self-recorded arterial pressure in essential hypertension in relation to the stage of the disease. In: Ediziono GG (ed): Blood Pressure Recording in the Clinical Management of Hypertension. Rome: Pozzi; 1985;pp 40-42.
7. Thijs L, Staessen JA, Celis H, et al. Reference values for self-recorded blood pressure: a meta-analysis of summary data. Arch Intern Med 1998;158:481-488.
8. Staessen JA, Den Hond E, Celis H, et al. Antihypertensive treatment based on blood pressure measurement at home or in the physician’s office: a randomized controlled trial. JAMA 2004;291:955-964.
9. 1999 World Health Organization.International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 1999;17:151-185.
10. White WB, Berson AS, Robbins C, et al. National standard for measurement of resting and ambulatory pressures with automated sphygmomanometers. Hypertension 1993;21:504-509.
11. O’Brien E, Waeber B, Parati G, Staessen J, Myers MG. Blood pressure measuring devices: recommendations of the European Society of Hypertension. BMJ 2001;322:531-536.
1. Fujiwara T, Matsubara M, Ohkubo T, Imai Y. Study Design of HOMED-BP: hypertension objective treatment based on measurement by electrical devices of blood pressure. Clin Exp Hypertens 2003;25:143-144.
2. Ohkubo T, Imai Y, Tsuji I, et al. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens 1998;16:971-975.
3. Bobrie G, Chatellier G, Genes N, et al. Cardiovascular prognosis of “masked hypertension” detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA 2004;291:1342-1349.
4. National Institutes of Health, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, MD: Public Health Service, NHLBI. NIH Publ. #03-5233, May 2003.
5. Brueren MM, Schouten JF, de Leeuw PW, van Montfrano GA, van Ree JW. A series of self-measurements by the patient is a reliable alternative to ambulatory blood pressure measurement. Br J Gen Pract 1998;48:1585-1589.
6. Verdecchia P. Reliability of home self-recorded arterial pressure in essential hypertension in relation to the stage of the disease. In: Ediziono GG (ed): Blood Pressure Recording in the Clinical Management of Hypertension. Rome: Pozzi; 1985;pp 40-42.
7. Thijs L, Staessen JA, Celis H, et al. Reference values for self-recorded blood pressure: a meta-analysis of summary data. Arch Intern Med 1998;158:481-488.
8. Staessen JA, Den Hond E, Celis H, et al. Antihypertensive treatment based on blood pressure measurement at home or in the physician’s office: a randomized controlled trial. JAMA 2004;291:955-964.
9. 1999 World Health Organization.International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 1999;17:151-185.
10. White WB, Berson AS, Robbins C, et al. National standard for measurement of resting and ambulatory pressures with automated sphygmomanometers. Hypertension 1993;21:504-509.
11. O’Brien E, Waeber B, Parati G, Staessen J, Myers MG. Blood pressure measuring devices: recommendations of the European Society of Hypertension. BMJ 2001;322:531-536.
Evidence-based answers from the Family Physicians Inquiries Network
Is pneumococcal vaccine effective in nursing home patients?
Evidence from clinical trials supports the use of pneumococcal polysaccharide vaccine for prevention of pneumonia in nursing home patients (strength of recommendation: B, based on randomized, nonblinded clinical trials).
Case-control studies have consistently shown the efficacy of pneumococcal vaccine in preventing invasive pneumococcal disease and bacteremia for patients with chronic medical illnesses and the elderly, patients typically found in nursing home populations (SOR: B, based on consistent case-control studies).
Evidence summary
Two clinical trials directly addressed the prevention of pneumonia in nursing home patients. A prospective, risk-stratified, randomized study of the 14-valent pneumococcal vaccine in 1686 patients living in hospices and nursing homes in France showed an absolute risk reduction (ARR) of 2.9% in the incidence of all-cause pneumonia, corresponding to a number needed to treat (NNT) of 35.1 This study has 2 major limitations: the authors did not comment on whether the study was blinded, and 31% of patients were lost to follow-up.
A 6-year randomized clinical trial that studied the trivalent pneumococcal vaccine in preventing pneumonia in New York City Home (a nursing home) subjects showed an ARR=2.7% and NNT=37.2 While this report also did not specify whether there was blinding, any bias introduced by absence of blinding is unlikely to account for the large effect size (relative risk reduction=0.56).
Nursing home residents may be especially vulnerable to acquiring pneumococcal infection due to advanced age, chronic illnesses, and their communal setting. The Centers for Disease Control and Prevention (CDC) has reported outbreaks of invasive pneumococcal disease in nursing homes where vaccination rates are low.3 Pneumococcal bacteremia is seen in only 10%–20% of patients with pneumococcal pneumonia but confers a significant risk of death. Therefore, pneumococcal vaccination is indicated for patients ≥ 65 years or those with chronic medical conditions.
Case-control studies have consistently shown efficacy in preventing invasive pneumococcal disease. Farr and colleagues found efficacy of 70% (95% confidence interval [CI], 37%–86%) among 2 groups of patients: those ≥ 2 years of age with chronic disease or those ≥ 65 years.4 A case-control study by Sims and colleagues also found the vaccine to have efficacy of 70% (95% CI, 37%– 86%) in preventing invasive pneumococcal disease in immunocompetent patients aged ≥ 55 years.5
Recommendations from others
The CDC Advisory Committee on Immunization Practices (ACIP) recommends pneumococcal vaccination of persons aged ≥65 years and those aged 2 to 64 who have chronic cardiovascular disease, chronic pulmonary disease, or diabetes mellitus (SOR: A).6
The ACIP also recommends the pneumococcal vaccine for persons aged 2 to 64 years who have alcoholism, chronic liver disease, or cerebrospinal fluid leaks (SOR: B).
The Canadian Task Force on Preventive Health Care endorses vaccination for immunocompetent patients 55 years residing in institutions (SOR: A).7
Paul Tatum, MD, MSPH
Department of Family Medicine, University of Colorado, Boulder.
The importance of pneumococcal vaccine for the elderly is well established. However, the vaccine is underused in long-term care settings, despite being indicated for most residents.
Patient confusion about the need for both influenza and pneumococcal vaccines, poor documentation of adult immunization status, poor availability of records from previous care facilities, and frequent changes in physician all contribute to low vaccination rates.
An optimal strategy to ensure high vaccination rates is to administer the pneumococcal vaccine to patients on admission to long-term care facilities. Patients who are uncertain about their vaccination status may safely receive the vaccine, as revaccination is relatively well tolerated.8
ACKNOWLEDGMENTS
The authors wish to thank Yves LeBlanc, MD, and Khalil Nasrallah, MD, for assistance with translation.
1. Gaillet J, Zmirou D, Mallaret MR, et al. Essai clinique du vaccin antipneumococcoique chez des personnees agees vivant en institution [Clinical trial of an antipneumococcal vaccine in elderly subjects living in institutions]. Rev Epidemiol Sante Publique 1985;33:437-44.
2. Kaufman P. Pneumonia in old age. Arch Intern Med 1947;79:518-31.
3. Centers for Disease Control and Prevention. Outbreaks of pneumococcal pneumonia among unvaccinated residents of a nursing home—New Jersey, April 2001. MMWR Morb Mortal Wkly Rep 2001;50:707-10.
4. Farr BM, Johnston BL, Cobb DK, et al. Preventing pneumococcal bacteremia in patients at risk. Arch Intern Med 1995;155:2336-40.
5. Sims RV, Steinmann WC, McConville JH, King LR, Zwick WC, Schwartz JS. The clinical effectiveness of pneumococcal vaccine in the elderly. Ann Intern Med 1988;108:653-7.
6. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 1997;46:1-24.
7. Wang EEL. Administration of pneumococcal vaccine. Canadian Task Force on Preventive Health Care 1994;385-6.
8. Jackson LA, Benson P, Sneller VP, et al. Safety of revaccination with pneumococcal polysaccharide vaccine. JAMA 1999;281:243-8.
Evidence from clinical trials supports the use of pneumococcal polysaccharide vaccine for prevention of pneumonia in nursing home patients (strength of recommendation: B, based on randomized, nonblinded clinical trials).
Case-control studies have consistently shown the efficacy of pneumococcal vaccine in preventing invasive pneumococcal disease and bacteremia for patients with chronic medical illnesses and the elderly, patients typically found in nursing home populations (SOR: B, based on consistent case-control studies).
Evidence summary
Two clinical trials directly addressed the prevention of pneumonia in nursing home patients. A prospective, risk-stratified, randomized study of the 14-valent pneumococcal vaccine in 1686 patients living in hospices and nursing homes in France showed an absolute risk reduction (ARR) of 2.9% in the incidence of all-cause pneumonia, corresponding to a number needed to treat (NNT) of 35.1 This study has 2 major limitations: the authors did not comment on whether the study was blinded, and 31% of patients were lost to follow-up.
A 6-year randomized clinical trial that studied the trivalent pneumococcal vaccine in preventing pneumonia in New York City Home (a nursing home) subjects showed an ARR=2.7% and NNT=37.2 While this report also did not specify whether there was blinding, any bias introduced by absence of blinding is unlikely to account for the large effect size (relative risk reduction=0.56).
Nursing home residents may be especially vulnerable to acquiring pneumococcal infection due to advanced age, chronic illnesses, and their communal setting. The Centers for Disease Control and Prevention (CDC) has reported outbreaks of invasive pneumococcal disease in nursing homes where vaccination rates are low.3 Pneumococcal bacteremia is seen in only 10%–20% of patients with pneumococcal pneumonia but confers a significant risk of death. Therefore, pneumococcal vaccination is indicated for patients ≥ 65 years or those with chronic medical conditions.
Case-control studies have consistently shown efficacy in preventing invasive pneumococcal disease. Farr and colleagues found efficacy of 70% (95% confidence interval [CI], 37%–86%) among 2 groups of patients: those ≥ 2 years of age with chronic disease or those ≥ 65 years.4 A case-control study by Sims and colleagues also found the vaccine to have efficacy of 70% (95% CI, 37%– 86%) in preventing invasive pneumococcal disease in immunocompetent patients aged ≥ 55 years.5
Recommendations from others
The CDC Advisory Committee on Immunization Practices (ACIP) recommends pneumococcal vaccination of persons aged ≥65 years and those aged 2 to 64 who have chronic cardiovascular disease, chronic pulmonary disease, or diabetes mellitus (SOR: A).6
The ACIP also recommends the pneumococcal vaccine for persons aged 2 to 64 years who have alcoholism, chronic liver disease, or cerebrospinal fluid leaks (SOR: B).
The Canadian Task Force on Preventive Health Care endorses vaccination for immunocompetent patients 55 years residing in institutions (SOR: A).7
Paul Tatum, MD, MSPH
Department of Family Medicine, University of Colorado, Boulder.
The importance of pneumococcal vaccine for the elderly is well established. However, the vaccine is underused in long-term care settings, despite being indicated for most residents.
Patient confusion about the need for both influenza and pneumococcal vaccines, poor documentation of adult immunization status, poor availability of records from previous care facilities, and frequent changes in physician all contribute to low vaccination rates.
An optimal strategy to ensure high vaccination rates is to administer the pneumococcal vaccine to patients on admission to long-term care facilities. Patients who are uncertain about their vaccination status may safely receive the vaccine, as revaccination is relatively well tolerated.8
ACKNOWLEDGMENTS
The authors wish to thank Yves LeBlanc, MD, and Khalil Nasrallah, MD, for assistance with translation.
Evidence from clinical trials supports the use of pneumococcal polysaccharide vaccine for prevention of pneumonia in nursing home patients (strength of recommendation: B, based on randomized, nonblinded clinical trials).
Case-control studies have consistently shown the efficacy of pneumococcal vaccine in preventing invasive pneumococcal disease and bacteremia for patients with chronic medical illnesses and the elderly, patients typically found in nursing home populations (SOR: B, based on consistent case-control studies).
Evidence summary
Two clinical trials directly addressed the prevention of pneumonia in nursing home patients. A prospective, risk-stratified, randomized study of the 14-valent pneumococcal vaccine in 1686 patients living in hospices and nursing homes in France showed an absolute risk reduction (ARR) of 2.9% in the incidence of all-cause pneumonia, corresponding to a number needed to treat (NNT) of 35.1 This study has 2 major limitations: the authors did not comment on whether the study was blinded, and 31% of patients were lost to follow-up.
A 6-year randomized clinical trial that studied the trivalent pneumococcal vaccine in preventing pneumonia in New York City Home (a nursing home) subjects showed an ARR=2.7% and NNT=37.2 While this report also did not specify whether there was blinding, any bias introduced by absence of blinding is unlikely to account for the large effect size (relative risk reduction=0.56).
Nursing home residents may be especially vulnerable to acquiring pneumococcal infection due to advanced age, chronic illnesses, and their communal setting. The Centers for Disease Control and Prevention (CDC) has reported outbreaks of invasive pneumococcal disease in nursing homes where vaccination rates are low.3 Pneumococcal bacteremia is seen in only 10%–20% of patients with pneumococcal pneumonia but confers a significant risk of death. Therefore, pneumococcal vaccination is indicated for patients ≥ 65 years or those with chronic medical conditions.
Case-control studies have consistently shown efficacy in preventing invasive pneumococcal disease. Farr and colleagues found efficacy of 70% (95% confidence interval [CI], 37%–86%) among 2 groups of patients: those ≥ 2 years of age with chronic disease or those ≥ 65 years.4 A case-control study by Sims and colleagues also found the vaccine to have efficacy of 70% (95% CI, 37%– 86%) in preventing invasive pneumococcal disease in immunocompetent patients aged ≥ 55 years.5
Recommendations from others
The CDC Advisory Committee on Immunization Practices (ACIP) recommends pneumococcal vaccination of persons aged ≥65 years and those aged 2 to 64 who have chronic cardiovascular disease, chronic pulmonary disease, or diabetes mellitus (SOR: A).6
The ACIP also recommends the pneumococcal vaccine for persons aged 2 to 64 years who have alcoholism, chronic liver disease, or cerebrospinal fluid leaks (SOR: B).
The Canadian Task Force on Preventive Health Care endorses vaccination for immunocompetent patients 55 years residing in institutions (SOR: A).7
Paul Tatum, MD, MSPH
Department of Family Medicine, University of Colorado, Boulder.
The importance of pneumococcal vaccine for the elderly is well established. However, the vaccine is underused in long-term care settings, despite being indicated for most residents.
Patient confusion about the need for both influenza and pneumococcal vaccines, poor documentation of adult immunization status, poor availability of records from previous care facilities, and frequent changes in physician all contribute to low vaccination rates.
An optimal strategy to ensure high vaccination rates is to administer the pneumococcal vaccine to patients on admission to long-term care facilities. Patients who are uncertain about their vaccination status may safely receive the vaccine, as revaccination is relatively well tolerated.8
ACKNOWLEDGMENTS
The authors wish to thank Yves LeBlanc, MD, and Khalil Nasrallah, MD, for assistance with translation.
1. Gaillet J, Zmirou D, Mallaret MR, et al. Essai clinique du vaccin antipneumococcoique chez des personnees agees vivant en institution [Clinical trial of an antipneumococcal vaccine in elderly subjects living in institutions]. Rev Epidemiol Sante Publique 1985;33:437-44.
2. Kaufman P. Pneumonia in old age. Arch Intern Med 1947;79:518-31.
3. Centers for Disease Control and Prevention. Outbreaks of pneumococcal pneumonia among unvaccinated residents of a nursing home—New Jersey, April 2001. MMWR Morb Mortal Wkly Rep 2001;50:707-10.
4. Farr BM, Johnston BL, Cobb DK, et al. Preventing pneumococcal bacteremia in patients at risk. Arch Intern Med 1995;155:2336-40.
5. Sims RV, Steinmann WC, McConville JH, King LR, Zwick WC, Schwartz JS. The clinical effectiveness of pneumococcal vaccine in the elderly. Ann Intern Med 1988;108:653-7.
6. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 1997;46:1-24.
7. Wang EEL. Administration of pneumococcal vaccine. Canadian Task Force on Preventive Health Care 1994;385-6.
8. Jackson LA, Benson P, Sneller VP, et al. Safety of revaccination with pneumococcal polysaccharide vaccine. JAMA 1999;281:243-8.
1. Gaillet J, Zmirou D, Mallaret MR, et al. Essai clinique du vaccin antipneumococcoique chez des personnees agees vivant en institution [Clinical trial of an antipneumococcal vaccine in elderly subjects living in institutions]. Rev Epidemiol Sante Publique 1985;33:437-44.
2. Kaufman P. Pneumonia in old age. Arch Intern Med 1947;79:518-31.
3. Centers for Disease Control and Prevention. Outbreaks of pneumococcal pneumonia among unvaccinated residents of a nursing home—New Jersey, April 2001. MMWR Morb Mortal Wkly Rep 2001;50:707-10.
4. Farr BM, Johnston BL, Cobb DK, et al. Preventing pneumococcal bacteremia in patients at risk. Arch Intern Med 1995;155:2336-40.
5. Sims RV, Steinmann WC, McConville JH, King LR, Zwick WC, Schwartz JS. The clinical effectiveness of pneumococcal vaccine in the elderly. Ann Intern Med 1988;108:653-7.
6. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 1997;46:1-24.
7. Wang EEL. Administration of pneumococcal vaccine. Canadian Task Force on Preventive Health Care 1994;385-6.
8. Jackson LA, Benson P, Sneller VP, et al. Safety of revaccination with pneumococcal polysaccharide vaccine. JAMA 1999;281:243-8.
Evidence-based answers from the Family Physicians Inquiries Network