effects of indapamide on the quality of life of hypertensive patients

Effects of Indapamide on the Quality of Life of Hypertensive Patients

DAVID GUEZ, M.D.

Neuilly-sur-Seine, France

LOUIS CROCQ, M.D. ALAIN SAFAVIAN, M.D.

Paris, France

PATRICE LABARDENS, M.D.

Neuilly-sur-Seine, France

From the Institut de Recherches Internationales, Servier, Neuilly-sur-Seine, France; Laboratoire de Psycho-Pathologie, Universite Paris V, Paris, France; and Centre de Diagnostic, Centre Hospitalier Universitaire, Broussais, Paris, France. Requests for reprints should be addressed to Dr. David Guez, Institut de Recherches Internationales Servier, 27, rue du Pont, 92202 Neuilly-sur-Seine Cedex, France.

This study analyzed the variation in the parameters characterizing the quality of life and well-being of hypertensive patients treated with indapamide. Thirty patients (10 men and 20 women; mean age, 52.5 +_- 2.1 years, SEM) were selected after a three-week observation period during which patients received placebo. They all had essential hypertension, defined as a diastolic blood pressure between 95 and 120 mm Hg. After the three-week placebo treatment period, indapamide was prescribed as single-agent therapy at a dose of one tablet per day (2.5 mg) for three months. The quality of life and the feeling of well-being of the treated subjects were analyzed on the basis of two self-assessment scales completed by patients and on the responses to a clinical observation scale completed during the consultation by the doctor. The decrease in blood pressure was significant (p <0.01) by the first month of treatment and the blood pressure was controlled (diastolic blood pressure less than 90 mm Hg) in 79.3 percent of patients by the third month. Statistical analysis of the modifications in the different scores demonstrated a significant improvement between the start and the end of the indapamide treatment period for the three types of scales (p <0.01). Analysis of the results also confirmed the homogeneous and significant concordance between the improvement in the responses to the doctor and patient scales. These results on the improvement in quality of life and well-being observed with indapamide demonstrate the importance of taking these aspects into consideration in the drug treatment for permanent essential hypertension.

Although all of the prospective studies have demonstrated the efficacy of antihypertensive drugs on the prevention of complications and the reduction of cardiovascular morbidity and mortality [1], the efficacy of treatment is limited by the lack of patient compliance, in other words the lack of concordance between the doctors' prescription and the acceptance of treatment by patients [2]. Haynes et al [3] reported that an average of 50 percent of hypertensive patients abandoned treatment during the first year. There are several explanations for this poor rate of compliance: the asymptomatic nature of hypertension in the majority of cases, the absence of real perception of the severity of the disease, the complexity and duration of treatment, and, most importantly, the unpleasant side effects.

Respect of the patient's quality of life and, consequently, his well-being is therefore one of the primordial factors in the fight against poor therapeutic compliance: it entails a reduction in the incidence of side effects common to numerous antihypertensive patients, such as induction of depression, reduction of libido, impotence, drowsiness, and limitation of

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SYMPOSIUM ON INDAPAMiDE--GUEZ ET AL

TABLE I Clinical Characteristics of the Patients on Inclusion into the Treatment Phase*

Parameters Values

Number of patients Women 20 Men 10

Age (years) 52.5 ± 2.1 Weight (kg) 71.1 ± 2.4 Hypertension already identified (%) 73 Duration of hypertension (years) 2.6 ± 0.6 Systolic blood pressure in sitting

position (mm Hg) 171.2 ± 2.5 Diastolic blood pressure in sitting

position (mm Hg) 101.9 ± 1.2

"Mean -+ SEM.

physical activity [4]; it is the result of a whole series of fundamental parameters: physical (everyday activities, sleep), social (work, family, others), emotional (joy of liv- ing, sexuality, well-being), and intellectual (memory, ca- pacity for adaptation), the combination of which is difficult to obtain. Levine and Croog [5] demonstrated that, after being informed of the diagnosis, hypertensive patients feel ill and vulnerable, although there is no relation between the psychologic state and hypertension in patients who have not been informed of the diagnosis. Similarly, Haynes et al [6] demonstrated that absenteeism from work increased in hypertensive patients informed of their disease in comparison with the overall population, regard- less of the severity of the hypertension. Last, Jachuck et al [7] demonstrated a reduction in quality of life in two of three patients treated with antihypertensives, despite the achievement of blood pressure control.

The principal aim of this study was to methodically evaluate the variation in the parameters of quality of life and well-being in hypertensive patients treated with indapamide by means of appropriate clinical scales.

PATIENTS AND METHODS

Recruitment of the Patients. The study was conducted in 30 patients (10 men and 20 women), between the ages of 30 and 70 years, who had uncomplicated essential hypertension, defined as a diastolic blood pressure between 95 and 120 mm Hg (in the sitting position after resting for at least 10 minutes and on three successive measurements over five minutes) (Table I). Patients presenting any of the following criteria were not included: history of allergy to sulfonamides and related drugs, renal or hepatic failure, cerebrovascular accident, ischemic heart disease, heart failure, diabetes, pregnancy, and concomitant use of drugs likely to interfere with the treatment of hypertension or the evaluation of the quality of life (psychotropic agents, for example).

The study was conducted on an outpatient basis in private practice in the Paris area after approval of the protocol by all

of the participating doctors. The patients were informed of the modalities of the study and gave their informed consent. Plan of the Study. After discontinuing administration of any antihypertensive agents previously prescribed, the patients were treated with placebo for a period of three weeks in order to confirm the permanent nature of the hypertension, its degree of severity, and the absence of complications, and in order to establish well-being scores in the hypertensive patients.

The 30 patients selected were treated for three months with indapamide 2.5 mg, one tablet per day and were re- viewed monthly for evaluation of the blood pressure in the sitting and standing positions (mercury sphygmomanometry, diastolic blood pressure at the phase V of Korotkoff) and measurement of the heart rate in the two positions; the consultation was held at the same time of day for each patient and was conducted by the same doctor.

The biochemical acceptability was evaluated by the serum creatinine concentration, fasting blood glucose level, serum potassium level, blood cholesterol level, and triglyceride concentration before and after treatment. Evaluation of Quality of Life. The quality of life in relation to the hypertension was investigated and evaluated at the end of the placebo period and at the end of the treatment period by means of three clinical instruments: an 11 -item clinical observation scale completed by the doctor, a self-assessment scale of 20 questions completed by patients, and a bipolar visual analogue scale, also completed by patients.

The "well being-ill being" clinical observation scale, espe- cially developed for this study, was adapted from two scales: clinical observation scale (for depressive asthenia) and a fatigue study group scale developed and validated, respectively, in 1973 and 1977 to 1983, by Crocq and Fondarai [8] and Crocq and Bugard [9] after being tested in several groups of asthenic and depressive patients. It contained the following 10 headings, which summarized the clinical history and the doctor's examination of the aspects of his patients "well- being": appearance, contact, muscular and sensory fatigue, functional visceral disorders, sleep, intellectual fatigue, emotion-mood, anxiety, vitality, and personality. It was completed by an eleventh heading of global evaluation (general well- being), susceptible to providing a different score from the mean of the scores of the 10 headings, since the global ap- proach did not necessarily coincide with the point-by-point inventary. Each of the 11 headings was scored according to a six-degree semiologic scale (or, more exactly, from degree zero plus five degrees) of increasing severity (0 means the symptom is absent; 1 is a mild symptom, and so on, up to 5 for a very severe symptom).

The self-assessment scale designed to explore the hypertensive patient's clinical well-being, inspired by several studies [10,11] and adapted for comparison with the clinician's observation scale, was presented in the form of a "questionnaire" of 20 assertions of ill-being associated with hypertension, based on the following headings: headaches and sensory symptoms, visceral symptoms, physical fatigue, intellectual fatigue, sleep, emotional state, anxiety, depression, vitality, sexual activity, and personality disorders. The patient had to evaluate each of these assertions depending on his or her current state, according to a six-degree scale.

54 January 29, 1988 The American Journal of Medicine Volume 84 (suppl 1B)

SYMPOSIUM ON INDAPAMIDE--GUEZ El" AL

The visual analo~]ue scale, used for the other evaluation of the global state of well-being and taking into account both the need for neutrality and the desire to respect the mental repre- sentations and the implicit metricity of the patient population, was presented in the form of a bipolar vertical axis with two arrows, representing well-being on the top and ill-being on the bottom. The middle-point of the axis was marked and 14 equidistant marks (seven on each side of the midpoint) in- vited a quantitative evaluation without suggesting a decimal reference. When completing this scale, the patient was asked to situate his or her condition by means of a cross on the axis. Statistical Analysis. Statistical analysis consisted of two- way analysis of variance for quantitative variables such as blood pressure, heart rate and biochemical results, and Wil- coxon's t test for qualitative variables such as the scores. This statistical analysis was designed to evaluate the degree of change between the score of the parameters defined before and after treatment, during which time each patient was compared with himself. In order to evaluate the effect of treatment in the overall condition, sums of the 10 scores obtained on the doctor's scale and of the 20 scores obtained on the patient's scale were calculated for each subject before and after treatment; the means of these totals were then compared by means of Wilcoxon's t test.

RESULTS

Variation in Blood Pressure and Biochemical Parame- terS. The 30 patients selected by the six general practi- tioners had a mean age of 52.5 +-- 2.1 years. After three weeks of p!acebo therapy, the mean systolic and diastolic blood pressures were, respectively, 171.2_ 2.5 and 101.9 --- 1.2 mm Hg in the sitting position with a heart rate of 81.6 - 1.6 beats/minute; in the standing position, they were, respectively, 168.1 -- 2.2 and 101.4 __ 1.2 mm Hg with a heart rate of 85.8 -+ 1.6 beats/minute. The values for the systolic and diastolic blood pressures in the sitting and standing positions were statistically significantly decreased by the first month of treatment and at each of the two following months; the mean decrease, in relation to the basal state, was 17.3/11.2 mm Hg at.the first month and 25.7/16.2 mm Hg at the third month in the sitting position (p <0.01 ). These variations were of the same order of magnitude for the values for blood pressure in the standing position. The heart rate was not modified to a clinically significant degree. No adverse effects were reported.

Biochemically, the serum creatinine, blood glucose, blood uric acid, and blood triglyceride levels were not modified during treatment. The serum potassium concentration was reduced by 0.32 mmol/liter, decreasing fr.om a mean of 4 . 2 7 - 0.05 to 3 .95 - 0.07 mmol/liter (p <0.001). The total blood cholesterol ievel was significantly reduced by 0.24 mmol/liter, decreasing from a mean of 6.25 ~- 0.18 to 6.01 - 0.18 mmol/liter (p <0.05). Variation in the Scores for the Clinical Observation Scale (Table II). The scale completed by the doctor consisted of 11 headings. The patient's appearance included facial expression, behavior, attitude, and gestures; the

TABLE II Variation in the Scores of the Clinical Scale*

Before After Parameters Indapamide Indapamide

Appearance 1.1 -+ 0.2 0.5 -+ 0.1 t Language, contact 1.0 -- 0.2 0.7 -- 0.2 t Physical and sensory discomfort 2.0 -+ 0.2 1.2 -+ 0.2 t Functional symptoms 1.9 --- 0.3 1.1 +- 0.2 $ Sleep disorders 1.7 +__ 0.2 1.3 +- 0.3 Intellectual fatigue 1.6 - 0.2 1.0 +- 0.35 Emotional reactions 1.9 --- 0.2 1.3 +- 0.3$ Anxiety 2.0 -- 0.2 1.3 -+ 0.35 Willpower, dynamism 1.6 --. 0.2 1.2 + 0.3 t Character, mood 1.8 -+ 0.2 1.2 -- 0.25 Well-being 1.9 +- 0.2 1.6 -+ 0.3

"Mean -+ SEM. tp <0.01. 5p <0.05.

score was significantly improved after three months, with a decrease in the mean from 1.1 to 0.5 (p <0.01). Lan- guage and contact were evaluated on the expressive qualities of these two parameters; they were significantly improved (p <0.05), with a decrease in the mean score from 1.0 to 0.7. The score for physical and sensory discomfort decreased statistically significantly (p <0.01) from 2.0 to 1.2; functional visceral symptoms were statistically significantly (p <0.05) improved, with the score decreasing from 1.9 to 1.1. The sleep disorders reported by the patients before treatment in the form of difficulty going to sleep, nightmares, difficulty waking, diurnal drowsiness, and nocturnal waking were decreased from a score of 1.7 to 1.3 (NS). The score for intellectual fatigue, covering items such as attention, memory, concentration, rational thought, clarity of ideas, temporospatial orientation, and slowed mental functions, improved from 1.6 to 1.0 (p <0.05).

The emotional reactions and mood of patients, the depressive tendency and thejr pessimism decreased statistically significantly from 1.9 to 1.3 (p <0.05). Anxiety, a primordial factor in the stability of blood pressure of hypertensive patients decreased from 2.0 to 1.3 (p <0.05) after three months treatment with indapamide. The .severity score for willpower and dynamism, which reflect vitality, initiative, projects, and decision, decreased significantly from 1.6 to 1.2 (p <0.05).

The personality of the hypertensive patients, evaluating sensitiveness, irritability, contrariness, aggressiveness, and anger, was considerably improved from 1.8 to 1.2 (p <.0.05)° Last, general well-being was improved, but not significantly, from ! .9 to 1 °6. Overall, all of the 11 parameters were favorably modified by indapamide and only two modifications were qot statistically significant. Evaluation of the Scores of the Patient Scale. Twenty parameters were analyzed (Table III) according to the

January 29, 1988 The American Journal of Medicine Volume 84 (Suppl 1B) 55

SYMPOSIUM ON INDAPAMIDE--GUEZ ET AL

TABLE III Variation in the Scores of the Patient Scale*

Before After Parameters Indapamide Indapamide

Headaches 1.7 -+ 0.3 0.6 ± 0.2 t Vertigo 1.0 ~ 0.2 0.6 ± 0.2 Ringing in the ears 1.1 ± 0.3 0.4 ± 0.1 t Visual disturbances 1.8 ± 0.2 0.6 ± 0.2 ~ Anorexia 0.8 ± 0.2 0.6 ± 0.2 Nausea 0.6 -+ 0.2 0.5 ± 0.2 Chest tightness 1.5 ± 0.3 1.2 _~ 0.3 Vasomotor disorders 1.5 -~ 0.3 1.3 ± 0.3 Tiredness on effort 1.9 ± 0.3 1.1 .+ 0.3 t Muscle cramps 1.0 ± 0.3 0.8 ± 0.2 Difficulties going to sleep 1.5 -+ 0.3 1.1 ± 0.3 Nocturnal agitation 2.0 -+ 0.3 1.2 ± 0.3 t Difficulties concentrating 1.7 +- 0.3 0.8 -+ 0.2 t Lack of dynamism and enterprise 1.7 .+ 0.3 0.8 = 0.3 t Emotional reactions 1.5 ± 0.3 1.0 ± 0.3 Depression 1.5 ± 0.3 1.0 ± 0.3 Anxiety 2.6 .+ 0.3 1.5 .+ 0.3 t Tired on waking 2.1 ± 0.3 1.3 ± 0.3 ¢ Irritability 2.0 -+- 0.3 1.1 .+ 0.3 t Decreased sex drive 0.9 ± 0.3 0.8 +- 0.3

• Mean .+ SEM. ~p .~0.01. ~p <0.05.

patient's responses to this scale without any intervention on the part of the doctor; the score for the most frequent incidence of functional discomfort decreased statistically significantly for headaches (p <0.01), ringing in the ears (p <0.01), visual disturbances (p <0.01), or non-significantly for vertigo, anorexia, vasomotor disorders, nausea, and feelings of chest tightness. Tiredness on effort and muscle cramps decreased (p <0.05 and nonsignificant, respectively). Sleep disorders regressed statistically significantly for nocturnal agitation (p <0.05) and nonsignificantly for difficulties going to sleep. Intellectual per- formances were improved, with less difficulty concentrating (p <0.05) and greater dynamism and enterprise (p <0.05). The scores for the psycho-affective state were improved nonsignificantly for emotion and depression and statistically significantly for anxiety (p <0.01 ), tiredness on waking (p <0.05) and irritability (p <0.01). Last, com- plaints concerning decreased sexual activity were less frequent after indapamide, despite the absence of statistical significance. Overall, all of the parameters were improved, half of them statistically significantly. Visual A n a l o g u e Scale of Well-Being. The self- assessment scale of well-being was completed by the patient just before the first consultation deciding definitive inclusion in the trial and just before each of the following consultations, i.e., a total of four times for each patient. The results after the third month of treatment revealed a marked and statistically significant improvement in the

well-being scale which increased from -0 .45 -- 0.57 to +2.17 _+ 0.45 (p <0.01). Evaluat ion of the C o n c o r d a n c e between the Scales. As defined in the protocol and in order to confirm the concordance of the variations in the different scores, we compared the 10 scores of the clinical observation scale and the 20 scores of the patient scale with the results of the visual analogue scale and the score for the eleventh item of global well-being, evaluated by the doctor.

The global evaluation of the clinical observat, ion scale, corresponding to the sum of the 10 items, decreased from a mean of 16.2 -+ 1.6 to 9.7 _+ 1.7 (p = 0.001). The global self-assessment by the patients, corresponding to the sum of the 20 scores, decreased from 27.0 _+ 3.4 to 16.2 -+ 3.5 (p <0.01).

These two scales revealed variations corresponding to a statistically significant overall improvement.

Only self-assessment of the visual analogue scale revealed a statistically significant improvement in well- being; the global score for well-being evaluated by the doctor did not vary significantly.

These findings are particularly interesting in that all of these scales investigated the same areas of quality of life, apart from appearance and contact, which were evaluated by the clinical observation scale. All three scales were concordant.

COMMENTS

The importance of evaluating quality of life in the course of drug treatment is becoming more and more generally ac- cepted [12].

Several earlier studies have examined evaluation of quality of life in treated hypertensive patients [6,10,13- 17]. Bulpitt and Fletcher [14] used a well-being questionnaire completed by the patients and the doctor, in order to evaluate their treated patients. In this group of 97 patients, the questionnaire was completed by the patients in 34 cases and by the doctors in 63 cases. Three aspects of well-being were taken into consideration by these authors: symptoms, activity, and psychologic state. They obtained a good correlation between the various aspects of well- being, allowing them to confirm the validity of the method. However, the questionnaire completed by the doctors was

-found to be less reliable due to the fact that it was less objective. Jachuck et al [7] also analyzed the influence of antihypertensive treatment on the quality of life of their patients. Questionnaires were completed by the patients, the doctors, and the patients' close entourage; each one was designed to determine whether patient quality of life was improved, unchanged, or aggravated. A marked dis- parity was observed between the patients' responses and the doctors' responses; according to the doctors, 100 percent of patients felt better, whereas an improvement was reported by only 48 percent of patients. More recently, a multicenter study [11] compared the effects of three anti-


SYMPOSIUM ON INDAPAMIDE--GUEZ ET AL

hypertensive therapies on quality of life; as very restrictive criteria of inclusion were applied, the authors recom- mended caution in the extrapolation of their results to other hypertensive populations. Despite these reserva- tions, this multicenter study demonstrated that well-being and quality of life differed according to the antihypertensive treatment used and that the tools used for its evaluation were sensible and reproducible enough to evidence differences. The clinical relevance of slight modifications in the quality of life was then established in a recent publi- cation by Testa [18].

The value of our study is largely due to the dual evaluation by the doctor and patients of the clinical parameters of quality of life. These results confirm those of previous studies conducted with indapamide [19,20] and complete the demonstrations of its antihypertensive activity and its acceptability, reported elsewhere [21-24]. However, the methodology differed from these studies due to the dual evaluation that reinforced the significance of the results.

The improvement in the clinical observation scale particularly concerned the physical and sensory discomfort, functional symptoms, and anxiety. These items were fol- lowed, in decreasing order, by appearance, intellectual fatigue, emotional control, character, and mood; finally, to a lesser degree, willpower, dynamism, and language were also improved. The classification of these results allows an evaluation of the validity and the indication profile for

the drug. In terms of validity, the items of physical and sensory discomfort, functional symptoms, and anxie.ty obtained the clinician's consensus. Similarly, intellectual fatigue, emotional control, personality, and mood obtained a more relative consensus. In contrast, items such as willpower and mood were more difficult to evaluate by non- psychiatrist clinicians. Physical, sensory, and functional discomfort and anxiety represent the essential elements of quality of life and well-being, whereas intellectual fatigue, emotional control, personality, and sleep are more closely related to the patient's own personality. The patient's self-assessment also revealed an order of priority of improvement fairly similar to that of the clinical observation scale, particularly for sensory and physical discomfort and anxiety. However, several differences appeared, for example, a better self-assessment of intellectual effi- ciency, character, and sleep. Other secondary similarities were also observed, such as emotional control and mood. The other symptoms raised problems due to their relative rarity (anorexia and cramps) and to their comprehension by the patient.

The results obtained with indapamide were therefore important because of the decree of concordance of the homogeneous and significant nature of the improvement in quality of life between the responses on the patient and doctor scales. The influence of quality of life in the modalities of medical management and therapeutic strategies for hypertension appears to be very important.

REFERENCES

1. Moser M, Black H, Stair D: The dilemma of mild hypertension. Drugs 1986; 31: 279-287.

2. Menard J, PIouin PF, Degouet P. Corvol P: Compliance to antihypertensive therapy. In: Amery A, Fagard R, Lijnen P, Staes- sen J, eds. Hypertensive cardiovascular disease: pathophysiology and treatment. The Hague: Martinus Nijhoff, 1982; 949- 966.

3. Haynes RB, Taylor DW, Sackett DL: Hypertension in the real world. In: Genest J, Kuchel O, Hamet P. Cantin M, eds. Hy- pertension. New York: McGraw Hill, 1983; 1252-1261.

4. Medical Research Council Working Party on Mild to Moderate Hypertension: Adverse reactions to bendrofluazide and pro- pranolol in treatment of mild hypertension. Lancet 1981; Ih 539-542.

5. Levine S, Croog SH: Quality of life and the patient's response to treatment. J Cardiovasc Pharmacol 1985; 7 (suppl 1): 132- 136.

6. Haynes RB, Sackett DL, Taylor DW, Gibson ES, Johnson AL: Increased absenteeism from work after detection and label- ling of hypertensive patients. N Engl J Med 1978; 299 (14): 741-744.

7. Jachuck S J, Brierley H, Jachuck S, Willcox PM~ The effect of hypotensive drugs on the quality of life. J R Coil Gen Pract 1982; 32: 103-105.

8. Crocq L, Fondarai J: Exploitation par ordinateurs des ~chelles

d'appreciation psychiatrique. Proceedings of the 71eme Congres de Psychiatrie et Neurologie de Langue Franqaise, Juillet 1973; Masson Ed. 1974; 403-415.

9. Crocq L, Bugard P: Fiche clinique standard pour I'appreciation des syndromes astheniques et de leur evolution. Psychol Med 1977; 9: 1757-1775.

10. Bulpitt C J, Dollery CT, Came S: Change in symptoms of hypertensive patients after referral to hospital clinic. Br Heart J 1976; 38: 121-128,

11. Croog SH, Levine S, Testa MA, et al: The effects of antihypertensive therapy on the quality of life. N Engl J Med 1986; 314 (26): 1657-1664.

12. Wenger NK, Mattson ME, Furberg CD, Elinson J: Assessment of quality of life in clinical trials of cardiovascular therapies. Am J Cardiol 1984; 54: 908-913.

13. Bulpitt C J: Quality of life in hypertensive patients. In: Amery A, Fagard R, Lijnen P, Staessen J, eds. Hypertensive cardiovascular disease: pathophysiology and treatment. The Hague: Martinus Nijhoff, 1982; 929-948.

14. Bulpitt CJ, Fletcher AE: Quality of life in hypertensive patients on different antihypertensive treatments: rationale for methods employed in a multicenter randomized controlled trial. J Cardiovasc Pharmacol 1985; 7 (suppl 1): 137-145.

15. Gill JS, Beevers DG: Hypertension and well-being. Br Med J 1983; 287: 1490-1491.

January 29, 1988 The American Journal of Medicine Volume 84 (suppl 1B) 57

SYMPOSIUM ON INDAPAMIDE--GUEZ El AL

16. Monk M: Psychologic status and hypertension. Am J Epidemiol 1980; 112 (2): 200-208.

17. Report by the Management Committee: The Australian therapeutic trial in mild hypertension. Lancet 1980; h 1261-1267.

18. Testa MA: Interpreting quality of life clinical trial data for use in the clinical practice of antihypertensive therapy. J Hyperten- sion 1987; 5 (suppl 1): $9-$13.

19. Watters K, Campbell DB: Can an antihypertensive agent both be effective and improve the quality of lite? A multicentre study with indapamide. Br J Clin Pract 1986; 40: 239-244.

20. Wheeiey MStG, Bolton JC, Campbell DB: Indapamide in hypertension: a study in general practice ol new or previously poorly controlled patients. Pharmatherapeutica 1982; 3 (2): 143-152.

21. Thomas JR: A review of 10 years of experience with indapamide as an antihypertensive agent. Hypertension 1985; 7 (6 part 2): 152-156.

22. Meyer-Sabellek W, Gotzen R, Heitz J, Arntz HR, Schulte KL: Serum lipoprotein levels during long-term treatment of hypertension with indapamide. Hypertension 1985; 7 (6 part 2): 170-174.

23. Gerber A, Weidmann P, Bianchetti MG, et ah Serum lipoproteins during treatment with the antihypertensive agent indapamide. Hypertension 1985; 7 (6 part 2): 164-169.

24. Chaffman M, Heel RC, Brogden RN, Speight TM, Avery GS: Indapamide--a review of its pharmacodynamic properties and therapeutic efficacy in hypertension. Drugs 1984; 28: 189-235.


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