Editorials

Our Role as Family Physicians in Vaccine Safety

RICHARD K. ZIMMERMAN, M.D., M.P.H.
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania

RICHARD D. CLOVER, M.D.
University of Louisville School of Medicine
Louisville, Kentucky

The success of the childhood immunization initiative in the United States is clearly demonstrated by the low incidence of vaccine-preventable diseases. With the widespread use of vaccines in the United States and the near-eradication of many childhood diseases that were common just a generation ago, parental concern has shifted from the harm and suffering caused by vaccine-preventable diseases to possible adverse events associated with vaccination.

Policies have changed over the past two years to enhance vaccine safety, as seen on the Recommended Childhood Immunization Schedule.¹ These changes include removal of thimerosal from infant doses of hepatitis B and Hib vaccines, use of the all-inactivated poliovirus vaccine series for poliomyelitis prevention, removal of rotavirus vaccine due to the risk of intussusception, and use of acellular diphtheria and tetanus toxoids and acellular pertussis vaccine instead of whole-cell diphtheria and tetanus toxoids and pertussis vaccine. Family physicians can take several measures to help with vaccine safety and preserve the public's confidence in vaccines.

First, provide patients or their legal guardian with the most current Vaccine Information Statement (VIS) before vaccination. Under the Public Health Service Act, health care providers who administer any vaccine containing diphtheria, tetanus, pertussis, measles, mumps, rubella, poliovirus, varicella, hepatitis B or Haemophilus influenzae type b antigens are required to provide a copy of the relevant VIS to the patient before vaccination. Every available VIS may be viewed and downloaded in multiple languages from the following Web sites: http://www.cdc.gov/nip/publications/VIS/default.htm or http://www.immunize.org/vis/index.htm. For vaccines that have no VIS available, physicians should provide information about the risk of the disease, the protection afforded from vaccination, the risk of vaccine adverse events and what to do if a serious adverse event occurs.

Second, report any adverse reactions temporally related to vaccination. Health care providers are required by federal law to report certain adverse events and should report any adverse events following vaccination to the Vaccine Adverse Event Reporting System (VAERS). VAERS forms and instructions may be obtained by calling 800-822-7967. This system received reports of cases of intussusception following rotavirus vaccination; this led to an investigation by the Centers for Disease Control and Prevention, which revealed the reaction and ultimately led to its withdrawal from the market.

Third, document the manufacturer, lot number, administration date and person administering the vaccine (including name, title and address) whenever a vaccine is administered. The ability to track vaccine failures or adverse events by lot number will enable authorities to determine whether incidents are lot-dependent or not.

As physicians, we can take comfort in the Vaccine Injury Compensation Program (VICP), which provides for no-fault compensation that can be awarded for specified injuries that are temporally related to administration of vaccinations against measles, mumps, rubella, diphtheria, tetanus, pertussis, poliovirus, hepatitis B, varicella or H. influenzae type b. For vaccines covered by the VICP, the program has reduced the risk of litigation for providers and vaccine manufacturers following adverse events. Information about specific adverse events that are covered is available from the Health Resources and Services Administration by telephoning 301-443-6593.

Richard K. Zimmerman, M.D., M.P.H., is an associate professor in the Department of Family Medicine and Clinical Epidemiology at the University of Pittsburgh School of Medicine with a secondary appointment in the Department of Health Services Administration.

Richard D. Clover, M.D., is chairman and professor of family and community medicine at the University of Louisville School of Medicine, Louisville, Ky.

Address correspondence to Richard K. Zimmerman, M.D., M.P.H., University of Pittsburgh School of Medicine, Department of Family Medicine and Clinical Epidemiology, M200 Scaife Hall, Pittsburgh, PA 15261.

REFERENCES

1. Recommended childhood immunization schedule-- January 2001 to December 2001. Am Fam Physician 2001;63:152-3.

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Increasing the Success of Antihypertensive Therapy

EDWARD D. FREIS, M.D.
Department of Veterans Affairs Medical Center and Georgetown University School of Medicine Washington, D.C.

Hypertension is the leading cause of patient visits to primary physicians.¹ However, there is reason for concern about how effectively this common condition is being treated. A recent national survey² found that only 27 percent of patients had their blood pressure reduced to less than 140/90 mm Hg, which is the therapeutic goal established by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI).³ Blood pressure reduction to less than 140/90 mm Hg is optimal for the prevention of cardiovascular complications.⁴ In patients with diabetes or renal disease, the recommended goal for blood pressure is 130/85 mm Hg or lower.

Why is hypertension uncontrolled in almost three-fourths of patients? The Canadian Coalition for High Blood Pressure Prevention and Control⁵ found that approximately 50 percent of patients are not compliant with taking their medications. A second major problem, according to a recent survey,⁶ is that 82 percent of physicians fail to increase doses when indicated.

The problems of patient adherence to therapy and inadequate dosing might be resolved using two-drug, fixed-dose combinations. This approach is supported by the results of several controlled clinical trials. The Veterans Affairs Trial⁷ was carried out testing patients whose blood pressure remained greater than 140/90 mm Hg following two successive monotherapies. They were then randomly assigned to a two-drug combination. All possible two-drug combinations among six major classes of antihypertensive medications were tested. The combinations containing a diuretic were more effective than any others, achieving a systolic blood pressure less than 140 mm Hg in 77 percent of these resistant patients and a diastolic blood pressure less than 90 mm Hg in 69 percent. This was a significantly greater reduction than occurred with other combinations, including a calcium channel blocker plus an angiotensin-converting enzyme inhibitor.

In another recent double-blind trial⁸ involving a fixed-dose combination of low-dose bisopterol, the beta-blocking drug, plus hydrochlorothiazide, 6.25 mg per day, was compared with standard doses of amlodipine or enalapril monotherapy. Goal blood pressure (diastolic blood pressure less than 90 mm Hg or a diastolic reduction greater than 10 mm Hg) was attained in 71 percent of patients taking the fixed-dose combination, 69 percent of patients receiving amlodipine and 45 percent of patients taking enalapril. Side effects were few with all drugs and were least with combination therapy.

The superiority of diuretic-containing combinations is demonstrated in other trials as well. The combination of hydrochlorothiazide plus captopril reduced systolic blood pressure by an average of 26.5 mm Hg and diastolic blood pressure by an average of 15.5 mm Hg.⁹ By contrast, a fixed-dose combination of diltiazem plus enalapril reduced diastolic blood pressure by an average of only 8.3 mm Hg. A list of five combination antihypertensives is provided in Table 1.

TABLE 1 Representative Fixed-Dose Antihypertensive Drug Combinations Combination drugs Trade name Beta-adrenergic blockers and diuretics   Atenolol-chlorthalidone Tenoretic Bisoprolol fumarate­hydrochlorothiazide Ziac Metoprolol tartrate­hydrochlorothiazide Lopressor HCT Nadolol-bendroflumethiazide Corzide Propranolol hydrochloride (extended release)­ hydrochlorothiazide Inderide LA Timolol maleate­hydrochlorothiazide Timolide ACE inhibitors and diuretics   Benazepril hydrochloride­hydrochlorothiazide Lotensin HCT Captopril-hydrochlorothiazide Capozide Enalapril maleate­hydrochlorothiazide Vaseretic Lisinopril-hydrochlorothiazide Prinzide Angiotensin II receptor antagonists and diuretics   Losartan potassium­hydrochlorothiazide Hyzaar Calcium antagonists and ACE inhibitors   Amlodipine besylate­benazepril hydrochloride Lotrel Diltiazem malate (extended release)­enalapril maleate Teczem Verapamil hydrochloride (extended release)­trandolapril Tarka Felodipine­enalapril maleate Lexxel Other combinations   Triamterene (37.5, 50 or 75 mg)­hydrochlorothiazide (25 or 50 mg) Dyazide Spironolactone (25 or 50 mg)­hydrochlorothiazide (25 or 50 mg) Aldactazide Amiloride hydrochloride (5 mg)­hydrochlorothiazide (50 mg) Moduretic Guanethidine monosulfate (10 mg)­hydrochlorothiazide (25 mg) Esimil Hydralazine hydrochloride (25, 50 or 100 mg)­ hydrochlorothiazide (25 or 50 mg) Apresazide Methyldopa (250 or 500 mg)­hydrochlorothiazide (15, 25, 30 or 50 mg) Aldoril Reserpine (0.125 mg)­hydrochlorothiazide (25 or 50 mg) Hydropres Reserpine (0.01 mg)­hydralazine hydrochloride (25 mg)­hydrochlorothiazide (15 mg) Ser-Ap-Es Clonidine hydrochloride (0.1, 0.2 or 0.3 mg)­chlorthalidone (15 mg) Combipres Methyldopa (250 mg)­chlorothiazide (150 or 250 mg) Aldoclor Reserpine (0.125 or 0.25 mg)­chlorthalidone (25 or 50 mg) Regroton Reserpine (0.125 mg)­chlorothiazide (250 or 500 mg) Diupres Prazosin hydrochloride (1, 2 or 5 mg)­polythiazide (0.5 mg) Minizide ACE = angiotensin-converting enzyme. Adapted with permission from Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2427.

Thiazide-containing fixed-dose combinations not only provide greater antihypertensive activity but also encourage compliance by providing a simple one-pill once-daily method of administration. In addition, small doses of each component in the combination diminish the occurrence of adverse reactions. Certainly, while physicians may be concerned about side effects, the threat is not nearly so great as the risk of major cardiovascular events resulting from inadequately controlled blood pressure.⁴ According to the Canadian Coalition,⁵ the most important intervention in this regard is patient education. Patients are advised that although they may feel healthy at present, a persistently elevated blood pressure increases the risk of developing strokes, heart attacks and heart or kidney failure in the future. Controlling high blood pressure reduces these risks.

Most fixed-dose combinations usually are available in two strengths, permitting some flexibility in dosage. The greater reduction in blood pressure associated with the thiazide-containing combinations than with other drugs is probably related to the volume-depleting effect of the diuretic,¹⁰ an action unique among various classes of antihypertensive activity of other medicines.

The hypertension control rate of only 27 percent indicates that present methods of antihypertensive treatment are faulty. Physicians can do better. Combination medicine containing a thiazide as one of the components and more attention paid to compliance could lead the way to improvement.

Edward D. Freis, M.D., is a staff physician at the Department of Veterans Affairs Medical Center, Washington, D.C.

Address correspondence to Edward D. Freis, M.D., Hypertension Research Clinic 151E, Veterans Affairs Medical Center, 50 Irving St., NW, Washington, DC 20422.

REFERENCES

1. Fisher G. Why patients visit doctors. Top 10 diagnoses based on office visits. Scott-Levin Physician Drug & Diagnosis Audit, 1998. Retrieved April 2000, from: http://www.scottlevin.com/news/rel_archive. cfm?rel_id=74&prsearch=.
2. Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey 1988-1991. Hypertension 1995;25:305-13.
3. The sixth report of the Joint National Committee on prevention, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413-46 [Published erratum appears in Arch Intern Med 1998;158:573].
4. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998;351:1755-62.
5. Chockalingam A, Bacher M, Campbell N, Cutler H, Drover A, Feldman R, et al. Adherence to management of high blood pressure: recommendations of the Canadian Coalition for High Blood Pressure Prevention and Control. Can J Public Health 1998; 89:15-11.
6. Sever PS. Blood pressure control for the hypertensive patient: what can we do better? Am J Hypertens 1997;10:128S-30S.
7. Materson BJ, Reda DJ, Cushman WC, Henderson WG. Results of combination anti-hypertensive therapy after failure of each of the components. Department of Veterans Affairs Cooperative Study Group on Anti-hypertensive Agents. J Hum Hypertens 1995;9:791-6.
8. Prisant LM, Weir MR, Papademetriou V, Weber MA, Adegbile IA, Alemayehu D, et al. Low-dose drug combination therapy: an alternative first-line approach to hypertension treatment. Am Heart J 1995;130:359-66.
9. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Captopril: evaluation of low doses, twice daily doses and the addition of diuretics for the treatment of mild to moderate hypertension. Clin Science 1982;63:4435.
10. Wilson JM, Freis ED. Relationship between plasma and extracellular fluid volume depletion and antihypertensive effect of chlorothiazide. Circulation 1959;20:1028-36.

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