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Effect of Adherence to Antihypertensive Medication on Stroke Incidence in Patients with Hypertension: a Population-Based Retrospective Cohort Study

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Open Access Research Effect of adherence to antihypertensive medication on stroke incidence in patients with hypertension: a population-based retrospective cohort study Hyo Jung Lee,1,2 Sung-In Jang,2,3 Eun-Cheol Park2,3 To cite: Lee HJ, Jang S-I, ABSTRACT Strengths and limitations of the study Park E-C. Effect of adherence Objective High blood pressure is a modifiable risk to antihypertensive medication factor for stroke, but non-adherence to antihypertensive on stroke incidence in ► This study reflects individual characteristics related medication is a growing concern for healthcare providers patients with hypertension: a to stroke, such as family history of stroke and population-based retrospective in controlling blood pressure. This study aimed to economic status. investigate the effect of adherence to antihypertensive cohort study. BMJ Open ► We indirectly measured adherence to 2017;7:e014486. doi:10.1136/ medication on stroke incidence. antihypertensive medication based on administrative bmjopen-2016-014486 Design Retrospective cohort study. claim data, which may not reflect the correct Setting We analysed National Health Insurance claim data Prepublication history and adherence. ► and check-up data from 2009 to 2013. additional material are available. ► This study may include selection bias as check-ups To view these files please visit Participants 38520patients with hypertension were in South Korea are voluntary and may be provided the journal online (http:// dx. doi. defined as those diagnosed with hypertension and by private hospitals rather than by National Health org/ 10. 1136/ bmjopen- 2016- prescribed antihypertensive medication. Insurance. 014486). Interventions No interventions were made. Outcome measure Poisson regression analysis using Received 28 September 2016 generalised estimating equations models was performed Revised 11 April 2017 to examine the association between adherence to persist or increase worldwide, including in Accepted 21 April 2017 antihypertensive medication and stroke incidence. South Korea, due to continuing industrial- Results Among 38 520 patients with hypertension, 957 isation, unhealthy lifestyles and an ageing (2.5%) strokes occurred during the study period. Non- population3 4. The most effective way to adherence to medication was significantly associated with reduce the socioeconomic burden of stroke a higher risk of stroke (intermediate adherence: adjusted is through preventive treatment of modifi- relative risk (aRR)=1.13, 95% CI=1.06 to 1.21; poor able risk factors.5 adherence: aRR=1.27, 95% CI=1.17 to 1.38). High blood pressure is one such modi- Conclusions Non-adherence to antihypertensive 6 7 medication in patients with hypertension was associated fiable risk factor . According to previous studies, hypertensive treatment reduces the with an increased risk of stroke. Therefore, healthcare 8 9 providers need to focus on interventional strategies to incidence of stroke by 30%–40% . Thus, ensure that these patients adhere to medication therapy hypertension control and the prevention of and to provide continuing support to achieve long- associated morbidity and mortality should 10 1 term adherence, ultimately minimising negative health be achievable. To do so, international and Department of Public Health, outcomes. Graduate School, Yonsei national guidelines have recommended University, Seoul, Republic of screening, treatment and control of high 11–14 Korea blood pressure. However, the preva- 2Institute of Health Services INTRODUCTION lence of uncontrolled hypertension remains Research, Yonsei University Stroke is responsible for 6.7 million (12.1% greater than 50% despite South Korea having College of Medicine, Seoul, of total) deaths per annum worldwide, higher rates of hypertension awareness, treat- Republic of Korea 15 16 3Department of Preventive and is the second most common cause of ment and control than the global average 1 Medicine, Yonsei University death after ischaemic heart disease. In (figure 1). College of Medicine, Seoul, South Korea, 24 486 per 100 000 individ- Therefore, it is important for healthcare Republic of Korea uals (9.1%) die of cerebrovascular diseases, providers to encourage patient adherence Correspondence to making it the third most common cause of to hypertensive treatment. Adherence to 2 Eun-Cheol Park; ecpark@ yuhs. death following cancer and heart disease. hypertensive treatment is defined as the ac This public health problem is expected to extent to which patients take medications, Lee HJ, et al. BMJ Open 2017;7:e014486. doi:10.1136/bmjopen-2016-014486 1 Open Access Figure 1 Comparison of hypertension awareness, treatment and control. follow diets or carry out lifestyle changes as per the MATERIALS AND METHODS advice of their healthcare providers, based on the treat- Study population ment alliance established between the patient and the 17 18 The South Korea National Health Insurance (NHI) healthcare provider. Most healthcare providers published cohort data, based on data from 2002, with are unlikely to doubt that the effect of hyperten- 1025 340 representative individuals randomly extracted sive treatment may be greater in patients taking their by stratifying for sex, age, employment status (employed medication as prescribed and conversely less in those or self-employed), income and individual total medical who do not. Although low adherence may result from costs. These data include claim data with details for poor blood pressure control in patients with apparent 19 20 patient's utilisation of healthcare and check-up data from resistant or refractory hypertension, a significant 2002 to 2013. The current study population included factor contributing to poor blood pressure control is patients with hypertension and aged over 30 years who that patients may not adhere to medication therapy as received a check-up between 2009 and 2013 and had no 21 prescribed. history of stroke before 2009. Patients with hypertension Studies regarding medication adherence and stroke were defined as patients who visited healthcare organisa- incidence in patients with hypertension have been tions with I10–I15 of the International Classification of 3 8 9 18 22–24 reported. However, only a few studies evalu- Diseases groupings (ICD-10) and received a prescription ating the relationship between medication adherence for antihypertensive medication (diuretics: ATC code and health outcomes have been conducted in South C03; beta-blocker: ATC code C07; calcium antagonists: 23 25 Korea. Therefore, the objective of this study was ATC code C08; ACE inhibitors and angiotensin antago- to investigate the effect of adherence to hypertensive nists: ATC code C09; and miscellaneous antihypertensive medication on stroke occurrence in South Korea using agents: ATC code C02). Patients who had a stroke in the nationally representative data. same calendar year as the diagnosis of hypertension were 2 Lee HJ, et al. BMJ Open 2017;7:e014486. doi:10.1136/bmjopen-2016-014486 Open Access excluded. Finally, data of a total of 38 520 participants Metabolic syndrome was diagnosed according to the obtained from 1 January 2009 to 31 December 2013 were revised National Cholesterol Education Program (NCEP) included in the analysis. This study was approved by the Adult Treatment Panel III criteria30. The NCEP criteria Institutional Review Board, Yonsei University Graduate suggest that metabolic syndrome meet at least three of School of Public Health (2014–239). This study did not the following components: (1) abdominal obesity (waist seek informed consent from patients as the datasets were circumference ≥90 cm for South Korean men or ≥85 cm completely anonymous and contained no personal infor- for South Korean women), (2) triglycerides≥150 mg/ mation related to the participants. dL, (3) high-density lipoprotein cholesterol ≤40 mg/dL for men or 50 mg/dL for women, (4) systolic/diastolic Measures blood pressure ≥130/85/85 mm Hg or (5) fasting plasma The outcome variable of this study was the incidence of glucose ≥100 mg/dL. Smoking status was categorised into stroke between 1 January 2009 and 31 December 2013. non-smoker, former smoker and current smoker. Dura- The incidence of stroke during the follow-up period was tion of hypertension was classified into the following determined by the first visit record from the time of the three groups: within 2, 2–5 and 5–10 years. stroke (ICD-10: I60–I64). To minimise reverse causation, patients with a history of stroke before 2009 were excluded Statistical analysis from the analysis. We determined the distribution of each categorical vari- The primary variable of interest related to stroke was able by examining frequencies and percentages, and that the adherence to antihypertensive medication, which was of the continuous variable by examining means and SD. In measured as the medication possession ratio (MPR). The addition, Poisson regression using generalised estimating MPR is based on the ratio of the number of days supplied equations (GEE), including confounders and interesting with medication to the total number of days in the year variables, was used to examine the association between before the study year.26 The MPR in the current study was stroke during the study period and each variable. Poisson calculated as follows: regression is typically used to model rare events, and repeated measures were considered.31 Subgroup analyses MPR = Number of days supplied by at least one during the year were also performed to assess whether the effect of medi- Number
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