In this study, the use of antihypertensive drugs in Japan, based on the NDB Open Data, was clarified for the first time using DID. Furthermore, there was a very strong positive correlation between the number of people with high systolic blood pressure and the DID among men and women aged 40–74 years. In addition, this study revealed, for the first time, the use of antihypertensive drugs in each prefecture of Japan. The methodology used in this study may be useful for the continued assessment of antihypertensive drug use and changes in the number of people with high systolic blood pressure based on the changes in antihypertensive drug use.

Antihypertensive drug use increased with age in both men and women (Fig. 1). This is thought to be partly because hypertension is more likely to develop with age owing to a decrease in vascular elasticity and baroreceptor reflex impairment [2]. Furthermore, a very strong positive correlation was found between the number of people with high systolic blood pressure and DID in both men and women aged 40–74 years (Fig. 3). In contrast, there was no significant correlation between the number of people with high diastolic blood pressure and DID (Fig. 3). It has been reported that progression of atherosclerosis leads to an increase in systolic blood pressure and a decrease in diastolic blood pressure, with the prevalence of isolated systolic blood pressure increasing and that of isolated diastolic hypertension decreasing with advancing age [2, 20]. Therefore, it is possible that the progression of arteriosclerosis associated with advanced age may be a contributing factor. In addition, the use of antihypertensive drugs was higher among men in the age group of 5–84 years and among women in the age group of 85 years and higher (Fig. 1). In the 30–79 years age group hypertension prevalence in men has been reported to be higher than that in women [21]. In addition, women have a longer average life expectancy [22], which may have contributed to this result.

In both men and women, DHP derivative Ca blockers (C08CA and C09DB) and ARBs (C09CA, C09DA, and C09DB) were the main drugs used from the age of 20 years (Fig. 2). These results are similar to those of a previous study using Diagnostic Procedure Combination (DPC) data [23]. Although the DPC data can only capture the use of drugs in some hospitals, the use of NDB Open Data has made it possible to capture the use of drugs nationwide. Guidelines for the management of hypertension in Japan [2] include Ca channel blockers, ARBs, ACE inhibitors, and diuretics as first-line drugs for hypertension management. Among these, DHP derivatives and Ca channel blockers have been reported to have strong hypotensive actions and have been indicated for many patients in Japan [2]. In addition, ARBs have organ-protective effects [24, 25], and the low frequency of adverse effects and high tolerability [26] associated with them are thought to contribute to their widespread use. However, the use of antihypertensive drugs varies across countries [5]. ACE inhibitors are mainly used in foreign countries [27, 28] but not so much in Japan. Dry cough, a side effect of ACE inhibitors, has been shown to develop more frequently in East Asians than in Caucasians [29]. Therefore, the use of ACE inhibitors is considered low in Japan.

Both men and women aged 0–19 years had higher rates of the use of ACE inhibitors, plain (C09AA), alpha- and beta-blocking agents (C07AG), and other drugs than those in their 20s and older (Fig. 2). Enalapril accounted for more than 90.9% of the use of ACE inhibitors plain (C09AA) in both sexes in the age group of 0–19 years (Fig. 2). Enalapril can be administered as early as 1 month of age. Therefore, enalapril is likely used more frequently than other antihypertensive drugs. Furthermore, carvedilol was the only alpha- and beta-blocking agent (C07AG) used in the age group of 0–19 years. In addition to hypertension, carvedilol is indicated for rapid atrial fibrillation, angina pectoris, and chronic heart failure due to ischemic heart disease or dilated cardiomyopathy. Because this study used ATC codes to classify antihypertensive drugs, it was not possible to evaluate the intended use of antihypertensive drugs with multiple indications, such as carvedilol. In the future, it will be necessary to establish a system for evaluating drug use.

A higher percentage of women in their 20s–40s used methyldopa (C02AB) than their mens’ counterparts (Fig. 2). Methyldopa is used more frequently in Japan because it is considered one of the first choices for the treatment of gestational hypertension in the Japanese guidelines for the management of hypertension [2]. In addition, ARBs are contraindicated in pregnant women [2] because of fetal and neonatal deaths and malformations that occur in patients who receive ARBs in the second and third trimesters of pregnancy [30, 31]. In this study, the rate of ARB (C09CA, C09DA, and C09DB) use was lower among women in their 20s–40s than in their mens’ counterparts (Fig. 2).

In this study, a large difference was observed in the use of antihypertensive drugs in each prefecture (Fig. 4), which was determined for the first time. In 2018, the Japanese Society of Hypertension set the goal of reducing the number of patients with hypertension by 7 million over 10 years and extending healthy life expectancy [32]. Previous reports have shown that the trend in drug use in more narrow regions such as municipalities differs from the national and prefectural usage trends [33]. Therefore, it is necessary to understand the trends in antihypertensive drug use in each region and implement appropriate countermeasures [33]. The methodology used in this study can be used to assess changes in the number of people with high systolic blood pressure based on the changes in antihypertensive drug use in a specific region. Therefore, targeted management is considered useful to reduce the number of patients with hypertension.

This study had several limitations. First, information on diagnoses was not available, and drugs prescribed for conditions other than hypertension may have been included in the study. Second, because NDB Open Data were used, factors not included in the data, such as public assistance, could not be considered. In addition, fewer than 1000 prescriptions were anonymized, which may have led to an underestimation of the use of antihypertensive drugs in Japan. Third, the number of people with high blood pressure calculated in this study was based on the results of the specific health checkups and may differ from the actual number of people with high blood pressure. Despite these limitations, this study is useful in understanding the use of antihypertensive drugs in Japan.