Albert Bakker

Impact of Dosage Frequency on Patient Compliance

OBJECTIVE To evaluate the impact of dosage frequency on the compliance of patients who receive their medicines from community pharmacies. RESEARCH DESIGN AND METHODS Each month, patients received a supply of their medication in a Medication Event Monitoring Systems container, which registered each opening of the package. At the end of the study, the patients received a short questionnaire. The subjects were 91 diabetic patients using oral antidiabetic agents. Patients taking insulin and those who were unable to collect their medicines from the pharmacy were excluded from the study. Compliance was defined as the percentage of doses taken during the observation period. Another parameter used was compliance with the prescribed regimen, defined as the percentage of days in which the number of tablets were taken as prescribed. As a last parameter, compliance with the prescribed dose intervals was used. RESULTS Compliance is influenced by the frequency of doses. The compliance for this group of patients is 74.8%, with an average of 79% in the case of a dose once daily and 38% in the case of a dose three times daily. The predominant type of noncompliance in all groups was dose omissions. However, more than one-third of the patients used more doses than prescribed. Overconsumption is a frequently made mistake by patients on a one-dose daily schedule. CONCLUSIONS The reduction of dose frequency may decrease total noncompliance, but at the same time, it increases the risk of overconsumption. Reducing the frequency does not automatically result in a better therapeutic schedule. The choice of once or twice daily should depend on the therapeutic range of the drug.

Influence of question structure on the recall of self-reported drug use.

Epidemiological studies often rely on self-reported information as a source of drug exposure. Several studies have evaluated the accuracy of self-reported information on drug use. The influence of question structure on the accuracy of recall, however, has not been studied extensively in these studies. In this study we examined the recall accuracy of questionnaire information on drug use in a ongoing public health survey with special attention to the influence of question structure on sensitivity of recall. A sample of 372 hypertensive subjects for whom questionnaire information and pharmacy records were available was examined. Self-reported information on drug use was obtained through questions about medications used for a specific condition and one final open-ended question. This information was compared with the pharmacy medication history. About 71% of all drugs that were currently in use according to the pharmacy records were recalled through the self-administered questionnaire, and 94% of all drugs mentioned in the questionnaire could be traced in the pharmacy records. Recall sensitivity was higher for questions about medications used for a specific indication (88%) than for the open-ended question (41%). The type of drug that was used might have caused part of this difference in recall. We conclude that questionnaire structure might be of influence on the accuracy of recall of self-reported drug use, and more attention should be paid to the structure of questions on drug use.

Measurement of patient compliance.

The compliance of 91 diabetic patients using oral antidiabetics was studied. Patient compliance was measured using four different methods. Patients received their medication in a Medication Event Monitoring System (MEMS)‐container. Each time the patient went back to the pharmacy for refill prescriptions, the number of tablets left in the container were counted. Pharmacy records were used to study the number of days of delay in getting the next refill. At the end of the study, a questionnaire was sent to every patient. Using MEMS as a standard, the results show that pill count and refill data overestimate the compliance of this group of patients. The MEMS data also show that the compliance data using only the number of tablets may be biased, because of possible overconsumption. Pill count does not show a correlation with compliance as measured by MEMS. The relation between compliance as measured with MEMS and refill compliance is weak.

Current use of thiazide diuretics and prevention of femur fractures.

A case control study of a defined population from The Netherlands was performed to evaluate the risk of femur fractures associated with the use of thiazide diuretics. Included were 386 patients hospitalized for femur fractures between 1986 and 1990 who were residents and 45 years of age and older. Per case, one age-, sex-, pharmacy-, and general practitioner-matched control was chosen from the general population. Drug use was ascertained from computerized pharmacy records. The adjusted odds ratio of current use of thiazide diuretics was 0.5 (95% confidence interval, 0.3-0.9). The protective effect of thiazide diuretics was greatest for use of 1 year or longer at relatively high doses of thiazides (odds ratio, 0.3; 95% confidence interval, 0.1-0.9). We also found that patients who discontinued thiazide use longer than 2 months were not protected against femur fractures. These results support the hypothesis that use of thiazide diuretics protects against femur fractures.

Excess Stroke Among Hypertensive Men and Women Attributable to Undertreatment of Hypertension

Background and Purpose —Most population-based studies indicate that a considerable proportion of hypertensive subjects are undertreated and that undertreatment is more prevalent among hypertensive men than among hypertensive women. The aim of our study was to investigate the consequences of undertreatment of hypertension for women and men in terms of stroke occurrence. Methods —Approximately 45 000 men and women aged ≥20 years were examined in 2 population-based studies in the Netherlands. A cohort of 2616 hypertensive subjects (pharmacologically treated hypertensives and untreated hypertensives who needed pharmacological treatment according to the severity of their hypertension and the coexistence of additional cardiovascular risk factors) was selected for a follow-up study. Follow-up (mean duration, 4.6 years) was complete for 2369 (91%) of the enrolled hypertensive subjects. Results —Compared with treated and controlled hypertensives, the relative risks of stroke for treated and uncontrolled hypertensives and for untreated hypertensives who needed treatment were 1.30 (95% CI, 0.70 to 2.44) and 1.76 (95% CI, 1.05 to 2.94), respectively. These relative risks and the prevalence of (undertreated) hypertension in the total population of 45 000 subjects were used to estimate the number of strokes in the Netherlands attributable to undertreatment. Among hypertensive men and women aged ≥20 years in the Netherlands, the proportions of strokes attributable to treated but uncontrolled blood pressure were 3.1% (95% CI, −5.2% to 18.7%) and 4.1% (95% CI, −7.2% to 20.7%), respectively. For untreated hypertensive men and women who should have been treated, these proportions were 22.8% (95% CI, 0.8% to 38.4%) and 25.4% (95% CI, 0.5% to 42.5%), respectively. Conclusions —Increasing the detection of hypertension and improving adherence to current guidelines might prevent a considerable proportion of the incident strokes among hypertensives. The potential impact of achieving control of blood pressure in patients already being treated on the reduction of strokes requires further investigation.

Sex differences in the pharmacological treatment of hypertension : a review of population-based studies

Objective To summarize all available literature on sex differences in the pharmacological treatment of hypertension with respect to the percentage of hypertensive patients treated pharmacologically and the selection of antihypertensive drugs. The influences of the calendar period, age, definition of hypertension, prevalence of hypertension and country on these sex differences were examined. Data identification A secondary analysis of data from 46 population-based studies in 22 countries on the prevalence of pharmacologically treated hypertension was conducted to estimate sex ratios for the prevalence of drug treatment for hypertension. Results Overall, women with hypertension were 1.33-fold [95% confidence interval (CI) 1.32–1.34] more likely to be treated pharmacologically for hypertension than were hypertensive men. With increasing age, the female : male ratio for pharmacological treatment of hypertension decreased from 2.26 (95% CI 1.56–3.27) at ages 20–29 years to 1.22 (95% CI 1.11–1.34) at ages 60–69 years. In all countries more women than men were treated for hypertension, with the biggest difference observed in the USSR (1983–1986), where about twice as many women as men were treated for hypertension. Women more frequently used diuretics, whereas men more often used β-blockers, angiotensin converting enzyme inhibitors and calcium antagonists. Conclusions Hypertensive women are more often treated for hypertension than hypertensive men and their pattern of use of antihypertensive drugs differs from that of men. Further research is required in order to explain sex differences in the treatment of hypertension with respect to the prevalence of pharmacological treatment of hypertension and choice of antihypertensive drugs, and to investigate the consequences of this difference for long-term outcomes.

Sex differences in antihypertensive drug use: determinants of the choice of medication for hypertension.

Objective To describe and explain sex differences in antihypertensive drug use. Design and methods From 1987 to 1995, two cross-sectional population-based surveys of cardiovascular disease risk factors in The Netherlands were carried out among 56 026 men and women aged 20–59 years. Polytomous logistic regression modelling was used to adjust for potential confounders of the association between sex and use of different antihypertensive drugs. Results The response rate was 40% for men and 46% for women. Of these respondents, 40% (1041) of the hypertensive men and 59% (1403) of the hypertensive women were being treated pharmacologically; 57% (595) of the treated men and 54% (760) of the treated women were on monotherapy for hypertension with a diuretic (men 14.8%, women 37.2%), a β-blocker (men 59.0%, women 45.3%), a calcium antagonist (men 8.6%, women 5.0%) or an angiotensin converting enzyme inhibitor (men 17.7%, women 12.5%). Among those on monotherapy for hypertension, women were less likely than men to be using a β-blocker [prevalence odds ratio (POR), female/male = 0.34; 95% confidence interval (CI) 0.24–0.47], a calcium antagonist (POR = 0.27, 95% CI 0.15–0.48) or an angiotensin converting enzyme inhibitor (POR = 0.34, 95% CI 0.22–0.52) than a diuretic. These sex differences persisted after adjustment for all factors that could have influenced the choice of these antihypertensive drugs (indications and contra-indications for the four antihypertensive drug classes). The sex differences in antihypertensive drug use were smaller among hypertensives with a history of cardiovascular disease (adjusted PORs, female/male, for β-blockers, calcium antagonists and ACE inhibitors, respectively, compared to diuretics were 0.80 with 95% CI 0.20–3.24, 0.40 with 95% CI 0.10–0.48 and 0.64 with 95% CI 0.12–3.39) than among those without such a history. Conclusions The different patterns of antihypertensive drug use among hypertensive men and women seem irrational, and cannot be explained by factors known to influence antihypertensive drug choice. Among hypertensives with a history of cardiovascular disease, the sex differences were smaller than among those without such a history. Further research is required to explain the sex differences in the choice of antihypertensive drug by prescribers, and to investigate the consequences of these differences for long-term patient outcomes.

Agreement between self‐reported antihypertensive drug use and pharmacy records in a population‐based study in The Netherlands

From 1987 to 1991, over 36,000 men and women aged 20‐59 years have been examined in the Monitoring Project on Cardiovascular Disease Risk Factors in The Netherlands. Classification of the treatment status of hypertensives in this population‐based study was based on self‐administered questionnaires. In order to assess the accuracy of self‐reported antihypertensive drug use we compared the questionnaire information with computerized pharmacy records from a sample of 372 hypertensive subjects. Most antihypertensive drugs that were mentioned in the questionnaire were present in the pharmacy medication history (93%). However, this percentage was less (76%) when a comparison was made with the calculated duration of use based on the number of units prescribed and the directions for use in the pharmacy records. About 94% of the hypertensive subjects who were using an antihypertensive drug according to the pharmacy records, also mentioned at least one antihypertensive drug in the questionnaire. Agreement between self‐reported antihypertensive drug use and pharmacy records was consistently high for all classes of antihypertensive drugs. Among 321 (86%) subjects, the number and types of self‐reported antihypertensive drugs were exactly the same as in the pharmacy records. In conclusion, the agreement between self‐reported antihypertensive drug use and pharmacy records was high, and the self‐reported questionnaire information on antihypertensive drug use can be reliably used for the classification of treatment status of hypertensive subjects in this population‐based study.

Angiotensin converting enzyme inhibitor associated cough: A population-based case-control study

The objectives of this study were to determine the risk for coughing as an adverse reaction to angiotensin converting enzyme (ACE) inhibitors under everyday circumstances in a large population and to study whether this adverse effect is more common in women. A population-based case-control study was used. The study was set in the practices of 161 Dutch general practitioners (GPs), in which all consultations, morbidity, mortality, medical interventions and prescriptions were registered during 4 consecutive 3-month periods in 4 consecutive groups of 40-41 GPs. The subjects were 2436 patients with incident coughing and up to 3 controls per case were obtained (total group: 7348 controls), matched for GP and a contemporary consultation in the same 3 months. All cases and controls were 20 years or older and had no notification of respiratory infections, influenza, tuberculosis, asthma, chronic bronchitis, emphysema, congestive heart failure, sinusitis, laryngitis, haemoptysis or respiratory neoplasms during the 3-month period. The results showed that cases were 3.6 times as likely as controls to have been exposed to ACE inhibitors (95% CI: 2.4-5.5) but after adjustment for potential confounders the odds ratio was 2.5 (95% CI: 1.6-3.9). The crude odds ratio for males was 2.7 (95% CI: 1.4-5.1) and for females 4.2 (95% CI: 2.4-7.5). The adjusted odds ratio for males was 1.8 (95% CI: 0.9-3.5) and for females 2.7 (95% CI: 1.5-4.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Usage patterns of benzodiazepines in a Dutch community: A 10-year follow-up

Only a few longitudinal studies have addressed benzodiazepine use over time. We therefore conducted a 10‐year follow‐up study (1983‐1992) on usage patterns of benzodiazepines in a Dutch community of 13500 people. Use decreased during the time of the study. Twelve (1983) to ten (1992) percent of the inhabitants was a recipient at least once a year of a benzodiazepine prescription. The use by gender showed more women using more prescriptions as men. Women were not prescribed more DDDs per prescription as men. Individual benzodiazepines showed differences in use by gender. Use increased with age among both women and men. Most of the users were 55 years or older. One out of three patients was either an incidental user (1‐30 days use in one calendar year), a regular (31‐180 days), or a long term user (more than 180 days). The use of long half‐life hypnotics decreased, the use of the short half‐life ones showed an increase. Behind a stable overall trend we found strong fluctuations in use of individual benzodiazepines.