Eur J Clin Pharmacol (2008) 64:1223–1229 DOI 10.1007/s00228-008-0495-5
PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Utilisation of angiotensin receptor blockers in Sweden: combining survey and register data to study adherence to prescribing guidelines Pia Frisk & Tor-Olov Mellgren & Niklas Hedberg & Anita Berlin & Fredrik Granath & Björn Wettermark
Received: 19 December 2007 / Accepted: 15 April 2008 / Published online: 15 August 2008 # Springer-Verlag 2008
Abstract Purpose Angiotensin receptor blockers (ARBs) offer a new treatment alternative for patients with hypertension and heart failure. Due to comparatively high prices, most guidelines suggest ARBs be restricted to patients intolerant to angiotensin-converting enzyme inhibitors (ACEi). We analysed the prescribing patterns of ARBs in Sweden by combining prescription register data with patient selfreported data. Methods Survey data from 517 patients dispensed ARBs in 55 pharmacies and data on dispensed prescriptions from the Swedish Prescribed Drug Register were used to study indication, comorbidity and whether ARBs were initiated as first-line treatment. Results In 2006, ARBs were dispensed to 3.6% of the Swedish population. The survey showed that 92% used them for hypertension. Register data showed that 23% of all P. Frisk (*) : A. Berlin National Corporation of Swedish Pharmacies (Apoteket AB), SE-118 81 Stockholm, Sweden e-mail:
[email protected] T.-O. Mellgren : N. Hedberg Swedish Pharmaceutical Benefits Board (LFN), Stockholm, Sweden F. Granath : B. Wettermark Karolinska Institutet, Centre for Pharmacoepidemiology and Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden B. Wettermark Karolinska Institutet, Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden
patients initiated on an ARB had not been prescribed any other antihypertensive drugs 1 year prior to the initiation. Conclusions ARBs are commonly used in Sweden, mainly to treat hypertension. Adherence to prescribing guidelines may be improved. Keywords Angiotensin receptor blockers . Drug utilisation . Guidelines . Prescribing . ACE inhibitors . Patient survey
Introduction Cardiovascular disease (CVD) is the leading cause of death worldwide [1]. It is a major health burden both in Europe and in developing countries. In Europe, more than 80 million people have a greater than 25% risk of a vascular event over a decade [1]. CVD also poses a great economic burden on health care. In the European Union, the total cost for CVD has been estimated at 169 billion euros annually, with health care accounting for 62% [2]. Consequently, there is an urgent need for effective and efficient cardiovascular prevention. Effective cardiovascular disease prevention includes lifestyle interventions and effective drug therapy to control important risk factors such as hypertension, hyperlipidemia and diabetes. A number of drugs have shown to be effective in controlling blood pressure and reducing morbidity and mortality [3, 4]. Angiotensin receptor blockers (ARBs) lower blood pressure by blocking AT1 receptors. They have a comparable effect on blood pressure with other antihypertensives, including angiotensin-converting enzyme inhibitors (ACEi) [3–5, 6]. Although there are no direct comparisons, large trials have demonstrated that ARBs are equally effective in reducing cardiovascular morbidity and mortality as other antihypertensive drugs [7–9].
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Since their introduction, ARBs have mainly been used to treat hypertension. This was estimated at 84% of all prescriptions of ARBs in Sweden in 2002 [10]. Since then, the indications for ARBs have been extended to include heart failure, left ventricular dysfunction after myocardial infarction and renal protection in patients with diabetes. Recent large trials have also shown that ARBs are equally effective compared with ACEi in the treatment of heart failure [11–13]. The side effects of ARBs are comparable with those of ACEi; however, unlike ACE inhibitors, ARBs do not cause coughing [6]. Prospective studies have shown that coughing occurs in approximately 10% of patients treated with ACEi. However, only 2–3% of all patients have left clinical trials due to this adverse event [14]. There is now a substantial price difference between ACEi and ARBs with the availability of generic ACEi. The treatment cost in Sweden for a generic ACEi is now typically less than one tenth the cost for an ARB, depending on product and dose. [15]. Consequently, guidelines suggest that ACEi should be the first choice for inhibition of the renin-angiotensin system in hypertension and/or heart failure, with ARBs only considered an option for patients intolerant to ACEi [5, 10, 16, 17]. ARBs have been heavily marketed, and sales have increased rapidly in many countries [10, 18–20]. However, information about the rationality of their prescribing is scarce. In this study, we used two different data sources to study the prescribing of ARBs in the Swedish population. This was part of a reimbursement review undertaken by the Swedish Pharmaceutical Benefits Board. The aim of the study was to monitor adherence to prescribing guidelines by studying prescribing indications for ARBs, whether ARBs were being prescribed for initial treatment of hypertension, whether and why patients were switched from other drugs to ARBs and to what extent patients treated with ARBs suffer from diabetes and/or renal impairment.
Eur J Clin Pharmacol (2008) 64:1223–1229
Data collection is administered by the National Corporation of Swedish Pharmacies, a state-owned company responsible for providing pharmaceutical services to the whole country. Information from all prescriptions dispensed is transferred monthly to the Centre of Epidemiology at the National Board of Health and Welfare, which is responsible for keeping the register. The register contains data on drugs dispensed, their amount, dosage, expenditure and reimbursement, as well as age, gender and unique identifier (personal identification number) of the patient. No clinical information on diagnoses/indications for treatment is recorded. In this study, drugs were classified according to the Anatomical Therapeutic Chemical (ATC) classification system [22]. Drug utilisation is expressed in defined daily doses (DDDs) and number of users per 1000 inhabitants [22, 23]. The period prevalence was assessed as the proportion of subjects in the Swedish population dispensed ACEi (ATC C09A and C09B) or ARBs (C09C and C09D) during 2006. The incidence was assessed using the waiting time distribution methodology, identifying first-time users of ACEi or ARBs after a drug free run-in period [24]. We studied dispensing each month in 2006 and used the last 4 months of 2006 to determine the incidence. This period was selected to exclude prevalent users and to avoid underestimation due to seasonal variation with lower sales during the summer (Fig. 1). Utilisation of other antihypertensive drugs was determined for the population initiated on ARB treatment in July–December 2006 by analysing each patient’s prescription of diuretics (ATC C03), beta blockers (C07), calcium-channel blockers (C08) and/or ACEi (C09A and C09B) 1 year prior to the first prescription of an ARB. The proportion of users of ACEi and ARBs that were diabetic patients was analysed using prescription of antidiabetic agents (ATC A10) to these patients in 2006 as a proxy for diabetes [25]. Patient survey
Methods The study consisted of two substudies: (1) analysis of data from the Swedish Prescribed Drug Register containing patient identity data on dispensed prescriptions of ARBs and ACEi to the entire Swedish population; (2) a survey distributed to a sample of patients dispensed ARBs at Swedish pharmacies. Register study Drug-dispensing data were collected from the Swedish Prescribed Drug Register [21]. The register contains data with unique patient identifiers for all dispensed prescriptions to the whole population of Sweden (9 million inhabitants).
The ability to connect a software for electronic surveys (EsmakerNX) to the product register of pharmacies and the system used for drug dispensation offers a method of collecting drug-related information directly from patients at the pharmacy counter. Based on prescription information such as age, gender and prescribed drug, patients meeting the entry criteria are automatically enrolled and offered a questionnaire at the end of the drug-dispensing process. In this case, an electronic questionnaire was offered to all patients presenting a prescription for an ARB in a representative sample of 55 community pharmacies throughout the country. The questionnaire was designed by the National Corporation of Swedish Pharmacies and the Swedish Pharmaceutical Benefits Board. It contained information about the purpose of the study, patient rights
Eur J Clin Pharmacol (2008) 64:1223–1229 14 12 "New" users/1000 inhabitants
Fig. 1 Waiting-time distribution for angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) in Sweden in 2006. Each bar represents first-time users. In the beginning of the period, all users purchasing their medicines are classified as new users. After a washout period, incidence can be determined. In this study, incidence was determined analysing the average number of new users in the 4 last months of 2006
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10 8 6 4 2 0 200601 200602 200603 200604 200605 200606 200607 200608 200609 200610 200611 200612
month
ACEi
and data safety and questions regarding the prescribed indication for the ARB, previous treatments for hypertension and prevalence of diabetes and renal insufficiency. Since the questionnaire did not capture any personal identifiers, Ethics Committee approval was not required. The questionnaire was offered to men and women of all ages during three randomly selected consecutive days (22– 24 May 2006). All ARBs (ATC C09C and C09D) were included in the survey. The pharmacies involved included six hospital pharmacies with dispensing services in ambulatory care, six pharmacies located in primary health care centres and several pharmacies in urban and rural areas. In addition to the survey data, complete prescription sales data for May 2006, covering the selected ATC categories in the whole country, were collected from the National Corporation of Swedish Pharmacies. Responders and nonresponders in the survey were compared with respect to age and gender using chi-square tests. Similarly, we compared the survey sample with the national prescription data with respect to age and gender distribution. Two-sided P values
