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Long-Term Persistence with Antihypertensive Drugs in New Patients

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Long-Term Persistence with Antihypertensive Drugs in New Patients Journal of Human Hypertension (2002) 16, 439–444 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh ORIGINAL ARTICLE Long-term persistence with antihypertensive drugs in new patients E Degli Esposti1, A Sturani2, M Di Martino3, P Falasca1, MV Novi1, G Baio4, S Buda3 and M Volpe5 1Health Directorate, Ravenna Local Health Unit, Ravenna, Italy; 2Hypertension Unit, Department of Nephrology, S.M. delle Croci Hospital, Ravenna, Italy; 3CliCon S.r.l., Health, Economics and Outcomes Research, Ravenna, Italy; 4University of Siena, R.M. Goodwin Faculty of Economics, EPRIS Research Group, Siena, Italy; 5Chair of Cardiology, Department of Experimental Medicine and Pathology, University ‘La Sapienza’, Rome, Italy The objective of this study was to investigate stay-on- 7.6% were restarted on a treatment in the third year. Per- therapy patterns over 3 years among patients pre- sistence with treatment was influenced by: age of scribed different classes of antihypertensive drugs for patient (persistence rate increasing proportionately with the first time. A retrospective analysis of information advancing years), type of drug first prescribed recorded in the drugs database of the Local Health Unit (persistence rate higher with angiotensin II antagonists, of Ravenna (Italy) was carried out on 7312 subjects progressively lower with ACE-inhibitors, beta-blockers, receiving a first prescription for diuretics, beta-blockers, calcium channel blockers and diuretics), gender of calcium channel blockers, angiotensin-converting patient (persistence was better in males), age of general enzyme (ACE) inhibitors or angiotensin II antagonists practitioner (GP) (the younger the GP, the better the per- between 1 January and 31 December 1997. Patients sistence rate) and gender of GP (better stay-on-therapy were followed up for 3 years. All prescriptions of antihy- rate with male GP prescribing). In the case of patients pertensive drugs filled during the follow-up periods treated continuously, mean daily dose increased pro- were considered. The patients continuing or discontinu- gressively over the 3 years. With adequate markers, ing the initial treatment, the duration of treatment, and helpful data can be collected from prescription claims the doses taken were all calculated, as well as main fac- databases for the purpose of monitoring the persistence tors influencing the persistence rate. The drugs pre- of patients in continuing their medication, and the qual- scribed were predominantly ACE-inhibitors, followed by ity of antihypertensive treatment in a general practice calcium channel blockers, diuretics, beta-blockers and setting. angiotensin II antagonists. A total of 57.9% of patients Journal of Human Hypertension (2002) 16, 439–444. DOI: continued their initial treatment during the 3-year follow- 10.1038/sj/jhh/1001418 up period, 34.5% discontinued the treatment, whilst Keywords: hypertension; antihypertensive drugs; administrative databases Introduction year and only two-thirds of those who remain under care take enough medication to control their blood Persistence with treatment is a crucial element in pressure.5,6 Many factors can influence the extent of determining the success of any long-term therapy. adherence to antihypertensive therapy. Persistence The full benefit of antihypertensive treatment 1–3 rates are inversely correlated with the number of observed in randomised clinical trials can be drugs prescribed, complexity of dosage regimen, and obtained only when hypertensive patients keep tak- with the cost of drug; whilst are directly correlated ing their medication as a matter of regular habit. with the tolerability of the treatment, and with a Frustratingly, low compliance remains a major strong and trusting physician–patient relationship.7 therapeutic problem in subjects treated for the first The aim of the present study was to investigate 4 time with antihypertensive drugs. Many patients stay-on-therapy patterns over 3 years, among with hypertension drop out of care inside the first patients who were receiving different classes of anti- hypertensive drugs for the first time. Correspondence: E Degli Esposti, MD, c/o CliCon S.r.l., Via San Materials and methods Vitale, 5, 48100 Ravenna, Italy. E-mail: edegliespostiȰiol.it Received 15 November 2001; revised and accepted 27 February This is a record linkage study, in which a retrospec- 2002 tive analysis was conducted using the database of Utilisation of antihypertensive drugs E Degli Esposti et al 440 dispensed drugs held by an Italian Local Health Unit received at least three prescriptions for drugs acting (LHU of Ravenna, Italy). LHUs are government on the cardiovascular system (ATC code: C01), and organisations which provide healthcare services to as asthmatic or having chronic obstructive pulmon- the entire population living in a given area and work ary disease (COPD) if they had received at least three toward the achievement of public health objectives prescriptions for respiratory drugs (ATC code: R03). pursued by the National Health Service (NHS). All The presence of cardiovascular diseases (acute myo- drug prescriptions written for the residents of cardial infarction, which is ICD 9 code 410, coronary Ravenna (approximately 350 000 inhabitants), tot- heart disease, ICD 9 code 411–414, heart failure, ICD ally or partially reimbursed by the NHS, are docu- 9 code 428–429) was determined by analysing hos- mented in the database. An automatically assigned pital admissions in the 5 years preceding inclusion national health number identifies each subject. in the study. Since 1 January 1996, the data file has been gather- ing all prescriptions dispensed, each bearing the NHS number, birth date and gender of the single Analysis of persistence patient. Also recorded, moreover, are the date of pre- We identified three patterns of persistence attribu- scription, the general practitioners (GPs) identifi- table to patients: cation code, the Anatomical-Therapeutic-Chemical (ATC) code of the drug/s, number of packs dis- (1) continuers—those who received at least two pre- pensed, number of tablets in each pack, milligrams scriptions for antihypertensive drugs during of active principle in each tablet, and cost per pack. each year of the 3-year follow-up period; The result is a database providing a long-term record (2) discontinuers—those who received at least two of all drugs prescribed for each patient. All infor- prescriptions for antihypertensive drugs during mation on antihypertensive drugs dispensed is col- the first year (lost in second year) or during the lected on a routine basis to enable computation of first and the second year (lost in third year) of the reimbursement payable to the pharmacists, who the follow-up period; supply the drugs to patients. (3) retreaters—those who received at least two pre- All patients enrolled in the present study were at scriptions for antihypertensive drugs during the least 20 years of age, and had been prescribed anti- first and the third year of the follow-up period, hypertensives for the first time in the period having suspended their therapy during the between 1 January 1997 and 31 December 1997, second year. namely diuretics (ATC code C03), beta-blockers (ATC code C07), calcium channel blockers (ATC For continuers, we also calculated the mean daily code C08), angiotensin-converting enzyme (ACE)- dose (MDD) (tablets/day) taken by each patient as inhibitors (ATC code C09A), or angiotensin II antag- the number of tablets of antihypertensive drugs pur- onist, ie losartan (ATC code C09C), which was the chased each year, divided by 365. only angiotensin II antagonist available in Italy dur- ing that period. Patients were excluded if they had Statistics received a prescription for any antihypertensive drug during the previous 12 months. Results are expressed as mean values (± standard Subjects were excluded if on the date of their first deviation). We performed all statistical analyses prescription they had been dispensed two or more using SPSS-Windows version 10.0 (SPSS Inc, classes of antihypertensive agents, or a combination Chicago, USA), considering P values less than 0.05 product including two different classes of antihyper- as significant. tensive drugs. Also excluded were those who had In the case of continuers, the hypothesis that received a single prescription or only two prescrip- mean daily dose is unaffected by 1 year’s stay-on- tions for the antihypertensive drugs considered in therapy was verified, in the case of continuers, using the present study, indicating a course of treatment a nonparametric Friedman test for dependent lasting less than 7 days. samples.8 Persistence was assessed using survival The observation period for each patient was 3 analysis methods.9 Having tested the proportional years starting from the date of the first prescription. hazards assumption, a Cox regression model was Patients who died or moved away during the follow- used: the number of days elapsing from the first to up period were excluded. Prescriptions for other the last prescription was taken as an estimate of the antihypertensive drugs filled during the follow-up duration of treatment, and the follow-up period was period, used in combination with or as substitutes limited to 1005 days. The following independent for the active principles studied in this paper, were variables were considered: age of patient, gender of also taken into account. patient, comorbidity if any, previous hospitalis- On the basis of prescriptions received in the year ations if any, class of drug prescribed at enrolment, preceding the period of inclusion in the study, administrative district, age and gender of GP, num- patients were defined as diabetic if they had ber of patients on the GPs list. The variables to be received at least three prescriptions for antidiabetic included in the model were selected thereafter drugs (ATC code: A10), as cardiopathic if they had adopting a stepwise method,10 which in the pro- Journal of Human Hypertension Utilisation of antihypertensive drugs E Degli Esposti et al 441 cesses of removal uses the Wald statistic (P- Table 1 Characteristics of the patients = = value(in) 0.05, P-value(out) 0.10).
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