Editorials

Combination Antihypertensive Drug Therapy: A Therapeutic Option Long Overdue

JOHN M. FLACK, M.D., M.P.H., and KAREN BLEDSOE, M.D.
Wayne State University School of Medicine and Detroit Medical Center,
Detroit, Michigan

See article in this issue.

Combination antihypertensive drug therapy has long been an infrequently exercised therapeutic option in the difficult battle to achieve target blood pressure levels. In this issue of American Family Physician, Skolnik and colleagues¹ present a timely discussion on the many merits of this therapeutic approach.

Until recently, the therapeutic goal in virtually all patients with high blood pressure was a blood pressure of less than 140/90 mm Hg. However, this target level typically has been achieved in fewer than 50 percent of medically treated patients.²

The evidence-based sixth report of the Joint Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI)³ appropriately assigned an even lower target blood pressure level (less than 130/85 mm Hg) for high-risk patients with renal disease, heart failure or diabetes mellitus. The rationale is that, at similar blood pressures, the absolute risk of morbidity and mortality from cardiovascular disease (as well as mortality from all causes) is much higher in these patients than in those who have hypertension and no comorbid conditions.

Over the years, target blood pressure levels have not been the primary subject of debate in hypertension therapy. Rather, debate has centered on the antihypertensive drug class that provides the greatest benefit to various subgroups of patients. The totality of evidence from clinical trials points to the following:

1. Initial therapy with antihypertensive agents from a multiplicity of drug classes with diverse pharmacologic effects (diuretics, beta blockers, calcium antagonists and angiotensin-converting enzyme inhibitors) has been shown to reduce blood pressure­related morbidity and mortality.^4-7

2. Monotherapy will be ineffective in most high-risk patients with hypertension, including those with renal failure, diabetes mellitus or stage 3 hypertension (blood pressures of 180/110 mm Hg or greater). These patients will require combination therapy to achieve blood pressure control to the level of 140/90 mm Hg or less.

3. Blood pressure control is probably more important than drug selection.

Drug selection is, however, important. Accordingly, one of the authors of this editorial (J.M.F) has argued previously that the concept of "preferred" drug therapy is more relevant to most practitioners in optimally integrating the concept of favored drug selection with the all-important goal of attaining the target blood pressure.⁸ Typically, a preferred drug is chosen for initial treatment. This drug is then titrated upward until the target blood pressure is achieved or the patient is being given the maximum tolerated dosage. When blood pressure control is not achieved, a second drug from a different class is added.

What does all of this have to do with combination drug therapy? Plenty. Therapy with the low to moderate doses of the two drugs in a combination agent more effectively lowers blood pressure than monotherapy with a higher dosage of either drug alone--and with fewer side effects.⁹

Given the newer, more appropriate lower target blood pressures for high-risk patients with hypertension, combination drug therapy will play an increasingly important role in attaining goal blood pressure. For example, the United Kingdom trial⁷ found that almost 30 percent of patients with type 2 diabetes and hypertension required three or more drugs to achieve an on-treatment blood pressure of 143/81 mm Hg (a systolic pressure fully 13 mm Hg higher than recommended in JNC VI³). Thus, it is relatively easy to deduce from available evidence that combination drug therapy will play an increasing role in achieving goal blood pressures.

The clinician is well advised to heed the important advice that Skolnik and colleagues¹ provide about the merits of combination antihypertensive drug treatment. The move to combination antihypertensive drug therapy, even as initial therapy, in high-risk patients with hypertension (particularly those with blood pressures in excess of 170/105 mm Hg, diabetes mellitus or renal insufficiency) is long overdue. The many benefits that will accrue from adoption of this therapeutic strategy include improved blood pressure control, fewer drug-induced side effects (including metabolic effects) and lower drug acquisition costs.

Dr. Flack is professor and associate chairman for Clinical Research and Urban Health Outcomes and director of the Cardiovascular Epidemiology and Clinical Applications Program at Wayne State University School of Medicine, Detroit, and Detroit Medical Center, Detroit.

Dr. Bledsoe is assistant professor in the Department of Internal Medicine at Wayne State University School of Medicine and Detroit Medical Center.

Address correspondence to John M. Flack, M.D., M.P.H., Department of Internal Medicine, Detroit Receiving Hospital/University Health Center 2E, 4201 St. Antoine Blvd., Detroit, MI 48201.

REFERENCES

1. Skolnik NS, Beck JD, Clark M. Combination antihypertensive drugs: recommendations for use. Am Fam Physician 2000;61:3049-56.
2. Burt VL, Cutler JA, Higgins M, Horan MJ, Labarthe D, Whelton P, et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population. Data from the health examination surveys, 1960 to 1991. Hypertension 1995;26:60-9 [Published erratum appears in Hypertension 1996;27:1192].
3. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997;157:2413-46 [Published erratum appears in Arch Intern Med 1998;158:573].
4. Staessen JA, Fagar DR, Thijs L, Celis H, Arabidze GG, Birkenhager WH, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997;350:757-64.
5. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703-13.
6. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-64.
7. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 1998;317:713-20.
8. Flack JM. Optimal blood pressure on antihypertensive medication. Current Hypertension Reports 1999;I:381-6.
9. Morgan TO, Anderson A, Jones E. Comparison and interaction of low dose felodipine and enalapril in the treatment of essential hypertension in elderly subjects. Am J Hypertens 1992;5:238-43.

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Child Abuse: The Physician's Role in Alleviating a Growing Problem

KIM BULLOCK, M.D.
Providence Hospital
Washington, D.C.

See article in this issue.

Child abuse and neglect are prevalent in American society. In many cases, the abuse is perpetuated generationally.¹ Child maltreatment, abuse and victimization refer to the intentional assault of a child by a caretaker. This definition has been expanded to cover any action that undermines a child's development potential and is a significant expansion of the definition associated with the battered-child syndrome.^2,3

Although the classic battered child who presents with multiple injuries can be easily identified by the family physician, it is a diagnostic challenge when no physical signs are apparent or the child has a single injury. For example, more than 60 percent of children who are sexually abused will not have physical indicators of abuse, thereby decreasing the value of the physical examination.⁴ In these situations, having an understanding of normal child development and behavior, along with recognizing the relationship between mechanism of injury and unintentional versus intentional trauma, are critical. Family physicians should also be aware of medical conditions that can be confused with abuse, for the outcome is tragic when a caretaker is falsely accused because of a child's illness.

Alternative medical practices have become increasingly common among children.^5,6 This may be especially true within immigrant and muticultural families. Among the more common regimens that have been used and are often confused with abuse are CaoGio, or coining, among Southeast Asians; bahnkes or cupping used among Russians, Koreans and others; and Caida de Mollera or fallen fontanella, among Latinos.⁷ In the case of coining or cupping practices, which are thought to draw infections from the body, erythematous and ecchymotic rounded lesions or linear streaks are produced on the body from a suction technique. A careful history taken by the family physician will disclose the correct etiology of the bruising and prevent an unnecessary social service investigation.

Fallen fontanella, a practice that involves turning a child upside down to correct a depressed fontanelle, can cause vomiting, diarrhea and dehydration in infants. Retinal hemorrhages can also occur, and sometimes shaken-baby syndrome is erroneously diagnosed.

Being culturally sensitive and alert to the ways parents and children deal with illness is important among diverse patient populations.

In this issue of American Family Physician, the clinical approach to the abused child is well covered in Pressel's article, "Evaluation of Physical Abuse in Children."⁸ The article is a good complement to a previous article in AFP by Bethea.⁹ Risk for serious injury and the prevalence of abuse trauma is highest in infants and young children, with the greatest fatalities occurring during the first several months of life.¹⁰ Family physicians must be familiar with development milestones during this period, because the risk of fatalities increases significantly when the diagnosis of child abuse is missed. Statistics reveal that neonaticide accounts for 45 percent of infant deaths within the first 12 months of life, making the newborn nursery evaluation, including parental acceptance of the infant and bonding, a critical component.¹¹

Child abuse in general is underreported, and vigilance on the part of family physicians is paramount. A recent study¹⁰ revealed that more than 80 percent of infant homicides are due to severe child abuse, and associated risk factors include young parental age at childbirth, birth of a subsequent child, and no prenatal care. According to the Third National Incidence Study of Child Abuse and Neglect (NIS-3), the birth order was strongly correlated with risk of physical injury.¹²

Armed with this information, it is clear that family physicians should inquire about risk factors for infant abuse during the prenatal period, with interventions initiated throughout pregnancy and the postpartum period. In addition, evidence shows that the risk of partner abuse may be greater during pregnancy and postpartum, especially among adolescent parents.

Screening for partner and infant abuse is therefore an important component of the history for family physicians during pregnancy and well-child visits. Screening for infant abuse is a priority when infant prematurity or disability exists, because of the increased risk of caregiver stress and decreased bonding.

The correlation between child abuse and domestic violence should also be emphasized. Studies have shown that in 45 to 50 percent of cases in which there is intimate partner abuse, there is also child abuse.¹³ Prevalence studies in a pediatric office and emergency department setting reveal that when mothers are questioned about domestic violence, as many as 30 to 50 percent report a personal history of abuse from their partner.^14,15

Child abuse may be a marker for domestic violence, suggesting the need for dual screening and intervention by family physicians. In order for this assessment and advocacy to be effective, family physicians must routinely ask about child abuse along with queries about domestic violence. The American Academy of Pediatrics (AAP) recommends that questions about domestic violence be a part of anticipatory guidance counseling.¹⁶ This type of brief, directed counseling has been shown to be effective and, when incorporated as part of the well-baby office visit, serves as a strategy for primary prevention. In addition to discussing age-appropriate safety issues in the home, the physician can facilitate discussion on the effect of conflict and violence on children, and nonviolent discipline techniques, and inform adult victims about abuse dynamics and safety planning. When appropriate, a physician may make referrals.

Violence witnessed by children is also a growing issue; between 3 million and 10 million children witness violence in their homes.¹⁷ This has been shown to produce a growing list of psychologic problems. Some of the effects include an increase in violence-related behavior and emotional activities, aggressive and disruptive responses in stressful situations, and an increase in undifferentiated abdominal pain, headaches and soft-tissue musculoskeletal pain.¹ Current studies have shown an association between witnessed abuse and health outcomes in children. Researchers reveal that witnessing domestic violence can be just as traumatic as sexual abuse, and children younger than 11 years are at a greater risk for post-traumatic stress disorder than adult witnesses.^18,19

A growing number of advocacy programs throughout the country offer treatment to children in this category and their families. Some offer home-based family counseling, while others have cross-trained health care professionals who can intervene and address both victims' needs. Family physicians should be familiar with and support such outreach agencies within their communities. These neighborhood-based programs serve as the best intervention and prevention services for families in crisis.

Kim Bullock, M.D., is a physician in the emergency department at Providence Hospital, Washington, D.C.

Address correspondence to Kim Bullock, M.D., Providence Hospital, 1150 Varnum St., N.E., Washington, D.C. 20017.

REFERENCES

1. Levy TM, Orlans M. Kids who kill. Forensic examiner 1999;8:19-24.
2. Kempe CH, Silverman FN, Steele BF, Droegmueller W, Silver HK. The battered-child syndrome. JAMA 1962;181:105-12.
3. Caffrey J. Multiple fracture in the long bones of infants suffering from chronic subdural hematoma. Am J Roentgenol 1946;56:163-73.
4. Monteleone JA. Child maltreatment: a clinical guide and reference. St. Louis: GW Medical Publishing, 1998.
5. Breuner CC, Barry PJ, Kemper KJ. Alternative medicine use by homeless youth. Arch Pediatr Adolesc Med 1998;152:1071-5.
6. Spigelblatt L, Laine-Ammara G, Pless IB, Guyver A. The use of alternative medicine by children. Pediatrics 1994;94:811-4.
7. Pachter LM. Cultural issues in pediatric care. In: Behrman RE, ed. Nelson Textbook of pediatrics. 14th ed. Philadelphia: Saunders Company, 1992:10-16.
8. Pressel DM. Evaluation of physical abuse in children. Am Fam Physician 2000;61:3057-64.
9. Bethea L. Primary prevention of child abuse. Am Fam Physician 1999;59:1577-85.
10. Overpeck MD, Brenner RA, Trumble AC, Trifiletti LB, Berendes HW. Risk factors for infant homicide in the United States. N Engl J Med 1998;339:1211-6.
11. Pitt SE, Bale EM. Neonaticide, infanticide, and filicide: a review of the literature. Bull Am Acad Psychiatry Law 1995;23:375-86.
12. Sedlak A, Broadhurst DD. Third national incidence study of child abuse and neglect: final report. Washington, D.C.: U.S. Dept of Health and Human Services, Administration on Children, Youth and Families, 1996:8-9.
13. Bullock KA, Schornstein SL. Improving medical care for victims of domestic violence. Hospital Practice 1998;34:42-58.
14. Siegel RM, Hill TD, Henderson VA, Ernst HM, Boat BW. Screening for domestic violence in the community pediatric setting. Pediatrics 1999;104:874-7.
15. Duffy SJ, McGrath ME, Becker BM, Linakis JG. Mothers with histories of domestic violence in a pediatric emergency department. Pediatrics 1999; 103:1007-13.
16. American Academy of Pediatrics, Committee on Child Abuse and Neglect. The role of the pediatrician in recognizing and intervening on behalf of abused women. Pediatrics 1998;101:1091-2.
17. Straus MA. Children as witnesses to marital violence: a risk factor for lifelong problems among nationally representative sample of American men and women. Paper presented at Ross Roundtable on Critical Approaches to Common Pediatric Problems. Washington, D.C., 1991.
18. Famularo R, Fenton T, Augustyn M, Zuckerman B. Persistence of pediatric post traumatic stress disorder after 2 years. Child Abuse Negl 1996;20: 1245-8.
19. Garbarino J, Kostelny K, Dubrow N. What children can tell us about living in danger. Am Psychol 1991;46:376-83.

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