Assessing Patient Wellness: New Perspectives on Quality of Life and Compliance Gordon H. Williams
Hypertension remains a major contemporary health problem in the United States despite being one of the most prevalent chronic diseases for which treatment is readily available. In spite of increased public awareness, active preventative campaigns, and notable progress in antihypertensive pharmacologic therapies, many patients remain untreated or inadequately treated. The reasons for this relative management failure are complex and multifactorial, and include the effects that pharmacologic agents have on quality of life. A patient’s overall level of well-being and perception of functional capacity may be more sensitive to the pharmacologic effects of antihypertensive agents than previously recognized. Compliance,
frequently related to a patient’s sense of deterioration in quality of life secondary to medical treatment, may well be the ultimate determinate of success with any antihypertensive regimen. Therefore, it is essential that clinicians implement pharmacologic therapy that balances biophysiologic needs with quality-of-life considerations to achieve the most successful and viable patient outcomes. Am J Hypertens 1998; 11:186S–191S © 1998 American Journal of Hypertension, Ltd.
Americans have hypertension.7 Although data from the National Health and Nutrition Examination Survey (NHANES) reveal dramatic improvements in public awareness, treatment, and control of hypertension from the period of 1976 to 1980 (NHANES II)8 to the period of the 1988 to 1991 survey (NHANES III),7 these trends have not sustained their promising outlook according to more recent data from the National Institutes of Health (NIH).9 Unfortunately, many people with hypertension are unaware of their condition, and many more remain untreated or inadequately treated.8 Research has established the effectiveness of antihypertensive therapy on morbidity and mortality statistics in patients with mild to moderate hypertension.1–11 In addition, there have been recent pharmacologic advances resulting in antihypertensive agents with more favorable safety, tolerability, and
ypertension is the most prevalent cardiovascular disorder in the United States (US). It remains one of the most common risk factors for cardiovascular morbidity and mortality despite heightened public awareness and advances in clinical management. Uncontrolled hypertension is well recognized as an important modifiable risk factor associated with coronary heart disease (CHD), stroke, congestive heart failure (CHF), end-stage renal disease (ESRD), and peripheral vascular disease (PVD).1– 6 Approximately 50 million adult
From the Harvard Medical School, Endocrinology/Hypertension Division, Brigham and Women’s Hospital, Boston, Massachusetts. Address correspondence and reprint requests to Gordon H. Williams, MD, Professor of Medicine, Harvard Medical School, Chief, Endocrinology/Hypertension Division, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115-5817.
© 1998 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
Hypertension, antihypertensive therapy, quality of life, compliance.
0895-7061/98/$19.00 PII S0895-7061(98)00196-4
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TABLE 1. MEASURES OF QUALITY OF LIFE Sense of well-being Physical symptoms • Sleep dysfunction • Sexual dysfunction • Work performance and satisfaction • Emotional status • Cognitive function • Social participation • Life satisfaction • •
efficacy profiles. Hypertension is one of the most prevalent chronic diseases for which treatment is readily available, yet nearly 70% of adult Americans with high blood pressure are not controlling their blood pressure to less than 140/90 mm Hg.8 Reasons for this relative management failure are multifactorial and include the effects that pharmacologic agents have on quality of life. Noncompliance, frequently related to a patient’s sense of deterioration in quality of life secondary to medical treatment, may well be the ultimate determinate of success with any antihypertensive regimen. The significance of this issue is highlighted by earlier data revealing that within each step of the hypertension management process, many patients fall out of the treatment tract; up to 50% of patients who begin treatment drop out of care within 1 year.14 Adherence with the treatment regimen (ie, compliance) has been described by many clinicians as a multilevel, multifactorial challenge and often a basis for lack of response to therapy. This complex behavioral process is strongly influenced by the patient’s environment, the healthcare provider, and the care the patient receives from the healthcare delivery system.12,13 Theories of compliance behavior include knowledge of and perception of seriousness of the disease process; individual perceptions of and value of health and wellness; motivation and capacity for change; degree of lifestyle change necessitated; social, psychologic, and economic factors; control and autonomy issues; presence of support systems; and impact the disease process has on the patient’s quality of life.13,14 One facet of hypertension management, assessment of quality of life, is an often-underevaluated outcome measure. Optimal pharmacologic management cannot simply be limited to objective findings from a patient’s physiologic and metabolic profile. Care of the hypertensive patient must also incorporate an assessment of quality of life, a concept that transcends documentation of drug side effects and appreciates a patient’s perception of functional capacity, productivity, and sense of well-being (Table 1).4 –17 In addition, clinically meaningful information may be obtained from individuals closest to the patient. Clearly, evaluation of
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both objective and subjective indicators of biomedical and quality-of-life outcomes are warranted when managing hypertensive patients. Appreciating quality-of-life indices within the context of clinical assessment is valuable. However, these indices must have established reliability and validity if they are to be of value to clinicians. For example, in 1986, 75 clinical trials appearing in five major North American journals cited the use of quality-of-life indices. However, only 11 of these studies fulfilled the usual criteria for a valid study (ie, a validated instrument, adequate sample size, and sufficient trial length). When evaluating a patient, an appropriate and sensitive tool must be utilized. In addition, instruments that incorporate ratings of both a psychosocial nature as well as physical symptom distress will be of the most value. When extrapolating data pertinent to quality of life, as with any other type of investigation, proper study design and methodology are crucial. Several studies examining quality of life associated with antihypertensive therapy have demonstrated hat quality of life can be meaningfully assessed and evaluated utilizing valid psychosocial measures.16,18 –27 Although significant findings have been documented between antihypertensive drugs and quality-of-life measures,16,18 –20,24,27 some investigators have found quality-of-life indices to improve after pharmacologic treatment.21,25,26 These findings support the need for a highly individualized antihypertensive pharmacologic management plan inclusive of a multilayered evaluation that incorporates quality-of-life measures. Jachuck and colleagues19 demonstrated that perceptions of quality of life may differ considerably in the estimation of the patient, individuals close to the patient, and the physician (Figure 1). Quality of life after antihypertensive therapy was evaluated in 75 patients (men: n 5 34; women: n 5 41; age range: 30 to 65
FIGURE 1. Assessment of the effects of antihypertensive therapy. Physician (diagonal bar), patient (solid bar), and relative (open bar). Adapted with permission from Jachuck SJ, et al. J R Coll Gen Pract 1982;32:103–105.
years) with controlled hypertension. The physician rated these patients as having achieved 100% improvement. Their blood pressure was adequately controlled, there had been no apparent deterioration in the patient’s clinical status, and the patients voiced no subsequent complaints regarding therapy. However, when the patients were queried, only 48% stated that they felt better, and 8% thought that they felt worse. In sharp contrast to both the physician and patient assessments, friends and relatives perceived still a different picture: 25% reported negligible to mild side effects, 45% reported moderate adverse changes, and 30% perceived that the patient had suffered severe impairment in quality of life after the initiation of antihypertensive therapy. Changes in affect (eg, outspokenness, tearfulness, tack, and dependence) were found to be minimal, but more than 50% of the patients who had severe impairment demonstrated changes in several faculties such as mood, preoccupation with illness, general activity level, and memory. It was observed that “energy” was impaired in 68% of the mildly affected group, and in 100% of the severely affected group. In addition, 78% of the severely impaired patients felt that sexual interest was reduced. In a multicenter, double-blind trial, Testa and colleagues20 documented the importance of quality-oflife assessments and consideration of third-party observations. Quality of life was evaluated in male patients with mild-to-moderate hypertension (n 5 394; age range: 35 to 70 years) randomized to received administration of either atenolol (n 5 193) or nifedipine gastrointestinal therapeutic system (GITS) (n 5 201). A 4-week period of washout with placebo was followed by 8 weeks of drug titration and 12 weeks of maintenance therapy. Hydrochlorothiazide (HCTZ) was added to the pharmacologic regimen to facilitate normalization of blood pressure, as needed. Both groups experienced similar control of blood pressure and total incidence of side effects, although withdrawal from the study was higher in participants receiving the nifedipine GITS due to peripheral edema. Survey results revealed more favorable global qualityof-life measures (eg, well-being, vitality, emotional control) in the nifedipine GITS group than in the atenolol group (P , .05). Perceptions of deterioration in quality of life secondary to medical intervention, adverse experiences, and efficacy issues were associated with withdrawal from the study (28% withdrawal in the nifedipine GITS group; 14% withdrawal in the atenolol group). In addition, spouses of younger participants receiving atenolol reported an increase in sexual dysfunction compared with the nifedipine GITS group (P , .02). Three surveys by Bulpitt et al18 comparing the symptoms of healthy controls and newly referred hypertensive patients were conducted to explore the re-
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lationship between symptoms thought to be related to the level of blood pressure and symptoms commonly associated with the side effects of antihypertensive therapy. Data were collected by self-administered questionnaire at the first medical visit and after 10 to 12 months. The groups consisted of patients from a long-term hypertension clinic (n 5 582), newly diagnosed hypertensive patients referred for outpatient follow-up care (n 5 212), and patients randomly selected from a local general medical practice (n 5 173). Symptoms from the untreated hypertensive patients, patients receiving long-term treatment in the hypertension clinic, and the normotensive controls were compared. At initial assessment, both the untreated and treated hypertensive patients complained of nocturia and feelings of physical unsteadiness. The untreated hypertensives reported symptoms of excessive depression, blurred vision, and headache upon waking. The treated hypertensive group reported more symptoms of sleepiness, dry mouth, diarrhea, and sexual dysfunction. Subsequent evaluation of these groups calculated the proportions of patients losing and gaining symptoms. Analysis of the data revealed that the relief of some symptoms (eg, headache and unsteadiness) was approximately counterbalanced by a gain in experience of side effects (nocturia and sleepiness) most likely associated with antihypertensive therapy; the average net improvement in symptoms was 2.0%. Croog and investigators16 demonstrated that antihypertensive agents can have different effects on quality-of-life measures and further supported that quality of life can meaningfully be assessed with available psychosocial measures (Figure 2). Patients with mild to moderate hypertension (n 5 626 men) participated in a multicenter, randomized, double-blind clinical trial to determine the effects of captopril, methyldopa, and propranolol on quality of life. HCTZ was added to the pharmacologic regimen to facilitate normalization of blood pressure, as needed. After a 24-week treatment period, all three groups experienced comparable control of blood pressure, and similar symptom scores for sleep dysfunction, visual memory, and social participation. As expected, overall quality-of-life measures were significantly higher in patients taking captopril compared with patients taking methyldopa (P , .05 to P , .01). Patients taking captopril had fewer side effects, experienced less sexual dysfunction, and had higher scores on measures of general well-being and life satisfaction, work performance, and cognitive functioning. In contrast, patients receiving methyldopa experienced statistically significant worsening of scores on measures of life satisfaction, depression, physical symptoms, work performance, and sexual dysfunction. The patients in the propranolol group experienced improvements in cognitive functioning
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FIGURE 2. Differential effects of captopril, methyldopa, and propranolol on quality of life. Comparison of mean 6 SEM rates of change 24 weeks from baseline for quality-of-life measures among the three treatment groups. **P , .01; *P , .05. Captopril (diagonal bar), methyldopa (open bar), propranolol (solid bar). Based on data in Croog et al.16
and social participation, but also experienced a worsening of scores on measures of physical symptoms and sexual dysfunction. The withdrawal rate due to medication side effects was lowest (8%) for patients taking captopril alone or in combination with a diuretic, compared with withdrawal rates for propranolol and methyldopa, which were 13% and 20%, respectively. This study illustrates the close association between compliance, reflected in withdrawal rates related to side effects, and medication-related effects on measures of quality of life. Testa et al24 explored whether effects on quality of life are uniform and clinically relevant within a specific class of pharmacologic agents. These effects were tested for further statistical delineation from concomitant adverse life events experienced by the patients (eg, loss of job, death of a spouse). Men with mild to moderately severe hypertension (n 5 379) participated in a multicenter trial comparing two angiotensin-converting-enzyme (ACE) inhibitors. After a 4-week washout period during which placebo was administered, the participants were randomly assigned to receive either captopril or enalapril, with or without HCTZ, for 24 weeks. Data were collected on blood pressure, quality-of-life indices, and life events, which were evaluated for differences between treatments by
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calibrating measures of quality of life with reports of objective life events (Figure 3). Analyses also included adjustment for baseline measures of quality of life. Results revealed no differences between the captopril and enalapril groups with regard to blood pressure control, frequency of withdrawal from the study, or major drug side effects. However, statistically significant differences were found in quality-of-life indices between the two drug regimens. Patients treated with captopril perceived more positive changes in global quality of life and general wellness measures, which included levels of vitality, sleep, and emotional control (P , .05). Patient ratings of quality of life varied consistently with baseline data. Patients with low perceived quality-of-life ratings remained stable or improved with either drug; patients with higher ratings of quality of life remained stable, but worsened with administration of enalapril (P , .001). Analysis of quality-of-life indices correlated with life events and symptom distress scores revealed that differences between the drug regimens were clinically significant (P , .001). These data are of value and interest to clinicians in that, between two drugs of the same pharmacologic class with similar safety and efficacy profiles, substantially different effects on quality of life are found. This indicates that drug-induced changes in quality of life and differences between treatment regimens are clinically meaningful. Again, this may ultimately translate into outcome measures affected by compliance related to a patient’s sense of deterioration in quality of life secondary to medical intervention. In another recent clinical trial,27 two commonly pre-
FIGURE 3. Calibration: quality of life v life events. Linear trend in psychological well-being as a function of negative life events. Reproduced with permission from Testa et al: Quality of life and antihypertensive therapy in men. A comparison of captopril with enalapril. N Engl J Med 1993;328:907–913.24
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potentially have on compliance with therapy, particularly when the perceived deterioration in quality of life is secondary to medical intervention. Given the many antihypertensive agents currently available, a cognizant clinician, in partnership with the patient, will be able to successfully formulate an antihypertensive pharmacologic regimen that not only meets biophysiologic needs, but is sensitive to the needs and concerns of patients and family members as well. REFERENCES
FIGURE 4. Physical symptom distress index scores. Change from baseline in standard deviation units for individual symptoms demonstrating a significant univariate treatment effect by treatment group (positive change reflects reduced distress; P 5 .002 for MANOVA). COER-Verapamil (n 5 252, solid bar), nifedipine GITS n 5 261, diagonal bar).
scribed calcium channel blockers were tested for effects on quality of life. Hypertensive patients (n 5 559) were randomized to receive either controlled-onset, extended-release (COER)-verapamil or nifedipine Gastrointestinal Therapeutic System (GITS). Data were collected on blood pressure and quality-of-life indices that included a symptom checklist, degree of symptom distress scale, and mental health index. The results revealed no differences between the two groups with regard to blood pressure control. It was found, though, as documented by Testa et al24, that effects on quality of life may not be uniform within a pharmacologic class of drugs. Highly significant treatment effects were found on all physical and psychosocial quality-of-life measure levels in favor of COERverapamil administration (P , .05) (Figure 4). The investigators note the potential significance that changes in quality-of-life measures may have on longterm compliance with an antihypertensive treatment regimen. The literature demonstrates that quality of life can meaningfully be assessed and evaluated utilizing valid psychosocial measures. A patient’s overall level of well-being, and perception of functional capacity may be more sensitive to the pharmacologic effects of antihypertensive agents than previously thought or recognized. In clinical practice, physicians need to balance therapeutic efficacy and safety with pharmacologic effects on wellness and quality of life. If adequate consideration is not paid to the latter, compliance with the prescribed regimen will likely suffer. Many studies reiterate the importance that patient’s place on quality-of-life issues and the effect this can
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