A cross-national study of the persistence of antihypertensive medication use in the elderly.

INTRODUCTION: Little is known about cross-national comparisons of the persistence of antihypertensive medication treatment, trends in persistence, and factors associated with persistence. The aim of this study was to describe and compare patterns of use of antihypertensive drugs in a population of elderly patients in the United States (Pennsylvania), Canada (British Columbia) and the Netherlands. METHODS: A retrospective cohort study of Medicare enrollees in a state pharmacy assistance programme in Pennsylvania (USA), residents from British Columbia (Canada) and residents from the Netherlands registered in the PHARMO database was conducted. Each population included patients 65 years and older who were initiated on blood pressure-lowering treatment between 1 January 1998 and 31 December 2003 and who had continuous follow-up for at least 365 days. In these populations, the proportion of patients with at least 180 consecutive days without medication available (non-persistence) were identified as were predictors of non-persistence using Cox proportional hazards. RESULTS: A total of 9664 Medicare enrollees (USA), 25 377 residents from British Columbia and 24 603 residents from the Netherlands were evaluated. During the first year after the initiation of treatment, the percentage of patients with at least 180 days without medication was 23.3% in Pennsylvania, 23.4% in British Columbia and 24.0% in the Netherlands. After 6 years, these percentages increased to 41.1, 36.3 and 38.2%, respectively. Factors associated with non-persistence were different between the three countries. CONCLUSION: Despite differences in factors associated with persistence, non-persistence patterns are strikingly similar in all three populations. This suggests that the problem of non-persistence transcends international boundaries.

Physician follow-up and provider continuity are associated with long-term medication adherence: a study of the dynamics of statin use.

BACKGROUND: Many patients who initiate statin (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) therapy discontinue treatment within 1 year. We sought to estimate the rate at which patients reinitiate treatment after long periods of nonadherence and to determine whether reinitiation of treatment is linked to potentially modifiable factors such as physician visits, cholesterol testing, or other encounters with the health care system. METHODS: We studied new users of statins in British Columbia, Canada, who initiated treatment between January 1, 1997, and June 30, 2004, and who had an extended period of nonadherence, defined as at least 90 days after the completion of 1 prescription in which no refill for any statin medication was obtained. Survival analysis was used to estimate the rate of reinitiation of statin therapy. Case-crossover analysis was used to evaluate the predictors of reinitiation. RESULTS: We identified 239 911 new users of statins, of whom 129 167 (53.8%) had a period of nonadherence that lasted for at least 90 days. Of these patients, an estimated 48% restarted treatment within 1 year and 60% restarted treatment within 2 years. Case-crossover analysis revealed events that were associated with a return to adherence, including visits with the physician who initiated the statin regimen (odds ratio [OR], 6.1; 95% confidence interval [CI], 5.9-6.3), a visit with another physician (OR, 2.9; 95% CI, 2.8-3.0), and a cholesterol test (OR, 1.5; 95% CI, 1.4-1.5). Incident myocardial infarction (OR, 12.2; 95% CI, 8.9-16.9) and other cardiovascular disease-related hospitalizations (OR, 3.6; 95% CI, 3.1-4.3) were also strong predictors of reinitiation of treatment. CONCLUSIONS: Physicians should be aware that statin use is dynamic and that many patients have long periods of nonadherence. A follow-up visit with the physician who wrote the initial statin prescription and having a cholesterol test predicted reinitiation of statin therapy. Our results suggest that continuity of care combined with increased follow-up and cholesterol testing could promote long-term adherence by shortening or eliminating long gaps in statin use. This hypothesis should be confirmed in a randomized experiment.

Rates and determinants of reinitiating antihypertensive therapy after prolonged stoppage: a population-based study.

OBJECTIVE: To assess patterns of restarting antihypertensive drugs after a prolonged period of discontinuation. METHODS: We conducted a retrospective cohort study among new users of blood pressure-lowering medication in the PHARMO database in The Netherlands, who had a period of at least 180 days without such medication. A multivariable Cox proportional hazard analysis was used to explore the baseline variables associated with reinitiating treatment. Case-crossover analysis was used to evaluate determinants of reinitiating treatment. RESULTS: We identified 35,714 patients as initiating blood pressure-lowering treatment during the period 1 January 1999 to 30 June 2004. Of the 18,357 (51.4%) patients who discontinued blood pressure-lowering treatment, 19.3% restarted treatment within 1 year and 60.7% restarted within 6 years. With every additional year they had been on therapy, patients were more likely to restart [odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.34-1.42]. The case-crossover analysis revealed that hospitalization for cardiovascular disease (OR = 2.20; 95% CI = 1.84-2.63), as well as refilling of another cardiovascular medication (OR = 1.25; 95% CI = 1.11-1.40), were each independently associated with reinitiating treatment. Refilling non-cardiovascular medications was not associated with reinitiating treatment (OR = 1.03; 95% CI = 0.97-1.10). CONCLUSION: Physicians should be aware that many patients have prolonged periods of discontinuation during the use of blood pressure-lowering medication, and that most of these patients will eventually resume therapy. Ongoing refilling other medications is not associated with reinitiating treatment. This suggests that, for some patients, the decision to discontinue may be drug specific rather than a behavioural characteristic applicable to all chronic treatments.

A comparison of two multiple-characteristic decision-making models for the comparison of antihypertensive drug classes: Simple Additive Weighting (SAW) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS).

BACKGROUND: Multiple-characteristics decision-making (MCDM) models can be used to calculate a score, based on a set of characteristics, for a number of alternative drugs or drug classes to allow comparison between them and thus enhance evidence-based pharmacotherapy. OBJECTIVE: To compare two MCDM models, Simple Additive Weighting (SAW) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), in determining first-line antihypertensive drug class. METHODS: Five different classes of antihypertensive drugs were analyzed: diuretics, beta-adrenoceptor antagonists (beta-blockers), dihydropyridine calcium channel blockers (DHP-CCBs), ACE inhibitors, and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). Four characteristics were deemed relevant for the determination of first-line antihypertensive drug class: effectiveness, persistence with treatment as a measure of tolerability, cost, and clinical experience. Weight factors were determined by sending questionnaires to cardiologists, pharmacists, general practitioners (GPs), and internists in The Netherlands. Absolute scores for the characteristics were determined from literature (effectiveness and persistence) and health insurance data (costs and clinical experience). RESULTS: Ninety-two cardiologists (33% of those sent the questionnaire), 90 GPs (31%), 87 internists (31%), and 123 pharmacists (43%) completed the questionnaire. Among all professions, according to both SAW and TOPSIS, ACE inhibitors were ranked as the first-line antihypertensive drug class, typically followed by beta-blockers. CONCLUSION: Both SAW and TOPIS analyses, using weight factors assigned by cardiologists, pharmacists, GPs, and internists from The Netherlands, rank ACE inhibitors as the first choice among antihypertensive drug classes for the treatment of uncomplicated hypertension. Both methods are valuable tools in the development of evidence-based pharmacotherapy.

Initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive therapy.

PURPOSE: Discontinuation with treatment is a major problem in the treatment of hypertension. The objective of our study was to assess the association between non-compliance and discontinuation in patients who started using antihypertensive monotherapy. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1st January 1999 and 31st December 2002 was performed. We used data from the PHARMO database, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 subjects. Cases discontinued their use of antihypertensive monotherapy and were not switched to other antihypertensive treatment, controls stayed on their initially prescribed monotherapy. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 9111 cases and 9111 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 14.0% and 5.8%, respectively [OR 2.86 (95%CI: 2.52-3.24)]. Patients who used less than 90 days had a higher risk on discontinuation [OR 3.10 (95%CI: 2.67-3.59)] than patients who used more than 90 days [OR 2.28 (95%CI: 1.79-2.92)]. The association was generally similar among males and females, among the different types of antihypertensives and among the different age groups. CONCLUSION: In patients who start antihypertensive monotherapy, non-compliance is often followed by discontinuation of this antihypertensive treatment. The pharmacy medication history is a valuable tool for physicians to identify patients who have a high risk on discontinuation with antihypertensive treatment.

All that glisters is not gold: a comparison of electronic monitoring versus filled prescriptions--an observational study.

BACKGROUND: Poor compliance with antihypertensive medication is assumed to be an important reason for unsatisfactory control of blood pressure. Poor compliance is difficult to detect. Each method of measuring compliance has its own strengths and weaknesses. The aim of the present study was to compare patient compliance with antihypertensive drugs as measured by two methods, electronic monitoring versus refill compliance. METHODS: 161 patients with a diagnosis of hypertension for at least a year prior to inclusion, and inadequate blood pressure control (systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg) despite the use of antihypertensive drugs, were included. Patients' pharmacy records from 12 months prior to inclusion were obtained. Refill compliance was calculated as the number of days for which the pills were prescribed divided by the total number of days in this period. After inclusion compliance was measured with an electronic monitor that records time and date of each opening of the pillbox. Agreement between both compliance measures was calculated using Spearman's correlation coefficient and Cohen's kappa coefficient. RESULTS: There was very little agreement between the two measures. Whereas refill compliance showed a large range of values, compliance as measured by electronic monitoring was high in almost all patients with estimates between 90% and 100%. Cohen's kappa coefficient was 0.005. CONCLUSION: While electronic monitoring is often considered to be the gold standard for compliance measurements, our results suggest that a short-term electronic monitoring period with the patient being aware of electronic monitoring is probably insufficient to obtain valid compliance data. We conclude that there is a strong need for more studies that explore the effect of electronic monitoring on patient's compliance.

Refill persistence with chronic medication assessed from a pharmacy database was influenced by method of calculation.

BACKGROUND AND OBJECTIVES: In literature, different methods of calculating persistence are used. In this study, the effect of using these different methods on persistence and the association of patients characteristics and persistence are assessed. METHODS: The PHARMO record linkage system was used to calculate persistence with antihypertensive drugs for a cohort of 14,466 new users of antihypertensives. Three different types of methods were used to define the maximum gap allowed between two prescriptions that a patient may have to be defined as a continuous user, one based on a defined number of days (varying from 9-365 days), the second based on the duration of the last prescription (varying from 0.1-4 times the duration), the third based on a combination of both methods, whichever leads to the lowest number of days. RESULTS: Refill persistence varied between 19.7-86.4% (method 1), between 27.9-90.2% (method 2), and between 19.7-86.4% (method 3). Furthermore, patient characteristics associated with persistence differed between and within the three different methods. CONCLUSION: The method used and the variation within a method influenced both persistence and the association between patient characteristics and persistence. Results of persistence studies are highly influenced by the researchers' method of the maximum allowed treatment gap.

Generic substitution of antihypertensive drugs: does it affect adherence?

BACKGROUND: Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. OBJECTIVE: To assess the association between generic substitution and nonadherence to antihypertensive drugs. METHODS: We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. RESULTS: Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. CONCLUSIONS: Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.

The association between compliance with antihypertensive drugs and modification of antihypertensive drug regimen.

BACKGROUND: Non-compliance is an important factor in lack of control of blood pressure. Uncontrolled blood pressure, as well as patients' complaints about the prescribed medication, may lead to modification of the initially prescribed antihypertensive drug regimen. The objective of this study was to assess the association between non-compliance and change in medication regimen. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1 January 1999 and 31 December 2002. We used data from the PHARMO database, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 subjects. Cases were subjects whose initial drug regimen was modified. Controls did not undergo such a modification. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI), and to adjust for confounders. RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 11,937 cases and 11,937 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 5.1 and 3.6%, respectively [OR 1.39 (95% CI: 1.22-1.58)]. The association is stronger in females [OR 1.64 (95%CI: 1.37-1.94)] than in males [OR 1.14 (95% CI: 0.94-1.40)] and stronger if the duration of episode of use is longer than 6 months. CONCLUSION: Non-compliance is significantly associated with the occurrence of change in antihypertensive medication regimen. Pharmacists and physicians can use pharmacy data, although data tend to overestimate actual compliance, to assess and improve compliance with antihypertensive drugs, before modifying treatment regimens.