ABSTRACT
Blood pressure control is important in post-stroke hypertensive patients and antihypertensive treatment is recommended for such patients. Ca-channel blockers are recommended as the medications of choice for the treatment of post-stroke patients. Here, we report the results of a large-scale prospective post-marketing surveillance study of post-stroke hypertensive patients (n = 2667, male 60.4%, 69.0 ± 10.9 years) treated with cilnidipine, with regard to blood pressure control and adverse reactions. Cilnidipine treatment caused a decrease in both clinic and home blood pressures 2 months after the beginning of treatment, and the decreased blood pressure was maintained until the end of 12 months’ observation. The proportion of patients in whom clinic blood pressure was well controlled (<140/90 mmHg) increased from 21.5% to 65.3% in cilnidipine treatment, with no differences in effectiveness among the various clinical subtypes of stroke. In total, 346 adverse events occurred, with an overall incidence of 8.9% (238 of 2667 patients). In the elderly group, specifically, a fall and a hip fracture each occurred in 1 (0.1%) patient. These results indicate that cilnidipine was effective in treating uncontrolled blood pressure and was well tolerated in Japanese post-stroke hypertensive patients in a real-world clinical setting.
Introduction
Hypertension is one of the most significant risk factors for the occurrence of stroke and blood pressure (BP) control is widely recognized as important for post-stroke hypertensive patients. For controlling BP in post-stroke hypertensive patients, both of the Japanese Guidelines for the Management of Stroke 2015 and the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 (JSH2014) recommended Ca-channel blockers (CCBs) as a grade A option for antihypertensive treatment (Citation1,Citation2). The 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the management of arterial hypertension also recommended CCBs as Class-I antihypertensive medications for post-stroke hypertensive patients (Citation3).
Cilnidipine is an L/N type CCB. Its antihypertensive effect and safety have already been reported for ambulatory BP control and lowering of clinic and home BP (morning and evening) based on prospective post-marketing surveillance (PMS) studies of cilnidipine (ACHIEVE-ONE study) and as used in hypertensive patients concomitantly with angiotensin II receptor blockers (ARBs) (Citation4–Citation6). However, PMS study of cilnidipine in post-stroke hypertensive patients has not been reported.
The Carotid Atherosclerosis-Antihypertensive Treatment Trial, Effect of N-type CCB for Cerebrovascular Disease (CA-ATTEND) study is a large-scale prospective PMS study in which the efficacy and safety of cilnidipine treatment were determined in registered post-stroke hypertensive patients, based on clinic and home BP measurements and atherosclerosis as evaluated by ultrasonographic examination of the common carotid arteries.
Here, we examined the BP control status and the incidence of adverse events in approximately 2700 Japanese post-stroke hypertensive patients receiving cilnidipine treatment in a real-world clinical setting.
Methods
Study design and patients
This study was conducted with the approval of the institutional review board (IRB) of Hiroshima University and, if necessary, the IRB or ethics committee of each participating medical institution; it was registered as a clinical study in the University Hospital Medical Information Network (UMIN000005523). This study was carried out according to the Good Post-marketing Study Practice (GPSP) established by the Ministry of Health, Labor and Welfare of Japan.
Participating physicians were recruited to this study from throughout Japan. The subjects were hypertensive patients who had a history of stroke and who started cilnidipine treatment for the first time between May 2011 and June 2013 in a real-world clinical setting. Although definitely or possibly pregnant women were excluded from this study, there were no limitations related to age or complications. No particular target level of BP control was stipulated, and there were no limitations to the class or dose of concomitant antihypertensive medications. Physicians who participated in this study registered eligible patients within 14 days from the beginning of cilnidipine treatment and recorded the patients’ characteristics, baseline and follow-up data via an electronic data capturing system (PostMaNet, Fujitsu FIP Corporation, Tokyo). Since this was a non-interventional study under real-world clinical setting, no written informed consent was required.
The observational period was 12 months. There were 7 observation time points: on the day treatment began, and 2, 4, 6, 8, 10, and 12 months after the baseline. The patient characteristics (sex, age, height, weight, history of stroke, and its subtypes, presence/absence and types of complications, laboratory data related to lifestyle-related disease, etc.), BP (clinic BP, home BP), pulse rate (PR), and concomitant drugs were recorded at baseline; BP (clinic BP, home BP) and PR were followed during the observational period. The subtype of stroke was defined by physicians according to the TOAST classification (Citation7). Adverse events were also recorded in the electronic data system by the participating physicians.
Each physician instructed patients to measure home BP according to the Japanese Society of Hypertension’s guidelines for self-monitoring of BP at home (Citation8), and each patient recorded their home BP data in a self-care note. Patients used electronic cuff oscillometric devices approved by the Ministry of Health, Labor and Welfare. Home BP was measured at each of the above seven observation time points. Home BP was measured twice a day, early in the morning (hereinafter called “morning”) and just before going to bed (hereinafter called “evening”).
Efficacy assessments
Efficacy variables included the changes from baseline in BP and PR (clinic and home) in all patients and stratified analysis according to patient characteristics or baseline data, such as with respect to each clinical subtype of stroke; the proportions of patients categorized by clinic BP and morning home BP; the proportions of patients achieving the BP targets recommended in JSH 2014; the proportions of patients achieving the BP targets in different clinical subtypes of stroke; and the proportions achieving the BP targets among patients with an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, patients with diabetes mellitus, or elderly patients aged 75 years or over.
Statistical analysis
The target number of subjects was determined to detect adverse reactions. In detail, the number of patients that would allow 95% power for the detection of at least 1 case of adverse reaction occurring at a frequency of 0.1% was calculated to be 3000, the target number of subjects in this study was set at 3000.
Data were expressed as mean ± standard deviation or medians (25th and 75th percentiles) for continuous variables and as frequencies and percentages for discrete variables. Changes in continuous variables from baseline to 12 months were tested using the paired t test. Changes in BP at 2, 4, 6, 8, 10, and 12 months after baseline were analyzed by Dunnett’s test. Changes in proportions were analyzed by Fisher’s exact test. In all tests, P < 0.05 (two-tailed) was regarded as significant. All statistical analyses were performed using a statistical software package (JMP, version 11.2.0; SAS Institute, Cary, NC).
Results
Subjects of analysis
In total, 3190 patients were registered (). Survey sheets were collected for 3130 patients but were not collectable for 60 patients. A total of 125 patients met our exclusion criteria, with the breakdown (including overlaps) being 66 cases of “no visit after the initial visit”, 48 cases of “no history of stroke”, 11 cases of “registry at 15 or more days after the beginning of treatment”, and 11 cases with other reasons. Of the remaining 3005 post-stroke patients who did not meet the exclusion criteria, 338 patients were registered within 7 days after the onset of stroke as an acute phase; thus, 2667 patients were included in the final analysis.
Figure 1. Breakdown of patients. Abbreviations: BP, blood pressure.
Patient characteristics
The patients’ mean age was 69.0 ± 10.9 years; the oldest age was 97 years and 33.6% of the patients were 75 years or older. Males accounted for 60.4%, and females for 39.6%. The patients were registered in this study at 1054 ± 1086 days after the onset of stroke. The modified Rankin Scale score was 1 (25th and 75th percentiles, 0–1). Clinic systolic BP was 152.2 ± 20.8 mmHg, and morning home systolic BP was 147.4 ± 17.1 mmHg. The clinical subtype of stroke was cerebral infarction in 80.6% of the patients, cerebral hemorrhage in 12.7%, and subarachnoid hemorrhage in 8.4%, including cases where more than one subtype of stroke was recorded in the same patient. Among the cases of cerebral infarction, small vessel occlusion was most frequent (42.3%), followed by large artery atherosclerosis (25.8%). At the beginning of cilnidipine treatment, 47.8% of the patients were already using other antihypertensive medications ().
Table 1. Patient characteristics.
Changes in BP and PR at clinic and home
Both clinic and home systolic and diastolic BP values had decreased after 2 months of treatment and remained low thereafter (). Both clinic and home PR values had decreased at 2 months and remained low thereafter. Changes from baseline after 12 months were 17.6 ± 21.5 and 9.1 ± 13.8 mmHg, for clinic systolic BP and clinic diastolic BP, respectively. Home BP also decreased after 2 months of treatment and remained low thereafter.
Figure 2. Time-course of changes in blood pressure and pulse rate. Abbreviations: BP, blood pressure; M, month or months; SBP, systolic blood pressure; DBP, diastolic blood pressure; PR, pulse rate. Data are presented as mean ± SD. *P < 0.05 vs. baseline (0M).
Morning home systolic BP values of <135 mmHg with clinic systolic BP values of <140 mmHg were classified as “normotension”, whereas morning home systolic BP values of ≥135 mmHg with clinic systolic BP values of ≥140 mmHg were classified as “sustained hypertension.” In this study, “normotensive” patients accounted for 11.9% (103 of 865 patients) at baseline, but increased to 40.5% (157 of 388 patients) at 4 months and 45.7% (235 of 514 patients) at 12 months of cilnidipine treatment. The proportion of patients with “sustained hypertension” was 64.2% (555 of 865 patients) at baseline, but decreased to 24.5% (95 of 388 patients) at 4 months and further to 18.7% (223 of 514 patients) at 12 months of cilnidipine treatment. Patients with “morning hypertension”, as defined by morning home systolic BP values of ≥135 mmHg, decreased from 80.9% (700 of 865 patients) at baseline to 43.4% (223 of 514 patients) at 12 months of cilnidipine treatment (P < 0.001, ).
Figure 3. Changes in the proportion of patients categorized by clinic blood pressure and morning home blood pressure at baseline (0M), and after 4 months and 12 months. Abbreviations: SBP, systolic blood pressure; M, month or months; *P-values are for differences between two groups.
Regardless of whether the clinical subtype of stroke was large artery atherosclerosis, small vessel occlusion, cerebral hemorrhage (hypertensive cerebral hemorrhage + other types of cerebral hemorrhage), or subarachnoid hemorrhage, clinic systolic BP and diastolic BP values had decreased after 2 months of cilnidipine treatment and remained low thereafter ().
Figure 4. Difference in the time-course of clinic blood pressure by the clinical subtype of stroke. Abbreviations: BP, blood pressure; M, month or months; SBP, systolic blood pressure; DBP, diastolic blood pressure. Data are presented as mean ±SD. *P < 0.05 vs. baseline (0M).
Hypertension control
Both clinic systolic BP and clinic diastolic BP were measured in 2370 patients at the time of registry. Although patients with BP values of <140/90 mmHg accounted for only 21.5% before cilnidipine treatment, the proportion was increased after 12 months of cilnidipine treatment. Antihypertensive medications other than cilnidipine were used in 53.5% (878 of 1642 patients) at 12 months of cilnidipine treatment. ARBs were used in 89.5% of these patients, diuretics in 18.6%, CCBs in 10.4%, β-blockers in 7.3%, ACE inhibitors in 5.2%, and α-blockers in 4.2% ().
Table 2. Blood pressure control status.
In 1119 patients, antihypertensive medications other than cilnidipine had already been used before cilnidipine treatment. Of these 1119 patients, ARBs were used in 86.7%, CCBs in 12.1%, ACE inhibitors in 5.9%, α-blockers in 3.7%, β-blockers in 6.6%, and diuretics in 17.0%. BP values were <140/90 mmHg in 24.8% of the patients who had been on other antihypertensive medications prior to cilnidipine treatment, and this proportion increased after 12 months of cilnidipine treatment. At 12 months of cilnidipine treatment in this group, antihypertensive medications other than cilnidipine were used in 97.3% (758 of 779 patients), with ARBs used in 89.7%, diuretics in 18.9%, CCBs in 11.3%, β-blockers in 7.4%, ACE inhibitors in 5.4%, and α-blockers in 4.1%.
The proportion of patients with BP values of <140/90 mmHg after 12 months of cilnidipine treatment was similar among the different clinical subtypes of stroke ().
In total, 815 patients were aged 75 years or older. BP values were <150/90 mmHg at baseline in 41.4% of these patients, but this proportion increased to 83.5% (474 of 568 patients) after 12 months of cilnidipine treatment (P < 0.001). Among patients who had been on other antihypertensive medications prior to cilnidipine treatment, BP values were <150/90 mmHg at baseline in 44.0% (177 of 402 patients), but this proportion increased to 79.7% (224 of 281 patients) after 12 months of cilnidipine treatment (P < 0.001). Among the 815 elderly patients, the proportion of those who had BP values of <140/90 mmHg was 24.0% at baseline, but increased to 66.9% (380 of 568 patients) after 12 months of cilnidipine treatment (P < 0.001). BP values were <140/90 mmHg at baseline in 26.6% (107 of 402 patients) who had already been on other antihypertensive medications prior to cilnidipine treatment, but this proportion increased to 60.1% (169 of 281 patients) after 12 months of cilnidipine treatment (P < 0.001).
Adverse reactions
In this study, 76 adverse reactions occurred, representing an incidence of 2.6% (69 of 2667 patients). There were 346 adverse events, representing an incidence of 8.9% (238 of 2667 patients). In total, 12 adverse events were deemed attributable to excessive lowering of BP: 7 cases of decreased BP, 3 cases of hypotension, and 2 cases of fainting. None of these adverse events were serious.
There were six cases of fracture and two cases of fall. Among patients aged 75 years or older (n = 815), there were four cases of fracture (rib fracture, spinal cord compression fracture, hip fracture, and fracture unspecified site) and one case of fall.
The incidence of cardiovascular adverse events was 0.3% (7 of 2667 patients). The incidence of cerebrovascular adverse events was 1.6% (42 of 2667 patients), mainly accounting for cerebral infarction (0.9%; 24 of 2667 patients), cerebral hemorrhage (0.3%; 8 of 2667 patients), and other cerebrovascular adverse events (0.4%; 10 of 2667 patients).
Discussion
In general, randomized controlled trials (RCTs) provide clinical results of scientifically high quality that allow guidelines to be established. However, because such results are usually obtained from a restricted dosing regimen in selected patients, it is difficult to generalize the demonstrated efficacy and safety (Citation9, Citation10). Therefore, such results have to be complemented by observational or surveillance studies before they are put to practical use in the routine clinical setting. However, to the best of our knowledge, there have been few reports to date of observational or surveillance studies of antihypertensive drug treatment focused on hypertensive patients with chronic stroke, involving medical institutions distributed over an entire country.
In this study, other antihypertensive medications were used with cilnidipine in about 50% of the patients. In particular, ARBs were used with cilnidipine in approximately 40%. Treatment with cilnidipine in addition to these concomitant drugs exerted a good antihypertensive effect on clinic and home BP in post-stroke hypertensive patients. Clinic systolic BP decreased steadily from 152.2 mmHg at baseline to reach 133.6 mmHg at 12 months, a mean decrease of 17.6 mmHg. Clinic diastolic BP decreased by 9.1 mmHg, from 85.2 mmHg at the baseline to 75.4 mmHg at 12 months. In an observational study, an analysis of UK clinic prescription data from the General Practitioner Research Database found that the recurrence of stroke was inhibited by antihypertensive medications (Citation11). Several meta-analyses of interventional studies in which antihypertensive medications were administered to prevent stroke recurrence have shown that decreases in BP are associated with a decreased risk of recurrence (Citation12–Citation14). In the PATS study, antihypertensive medication treatment in Asian post-stroke patients decreased clinic systolic BP by 12 mmHg, from 154 mmHg to 142 mmHg, achieving a 29% decrease in stroke recurrence (Citation15). In the PROGRESS study, antihypertensive medication treatment decreased clinic systolic BP by 9 mmHg, from 147 mmHg to 138 mmHg, achieving a 28% decrease in stroke recurrence (Citation16). The magnitude of the decrease in clinic BP after cilnidipine treatment in this study was similar to those in the above studies.
Cilnidipine treatment exerted a favorable antihypertensive effect on home BP in post-stroke hypertensive patients. Home BP is a better predictive factor for cardiovascular death and overall death than clinic BP (Citation17,Citation18). Therefore, JSH 2014, the 2013 ESH/ESC Guidelines for the management of arterial hypertension, and the 2015 Canadian Hypertension Education Program recommendations (Citation19) all recommended the use of home BP in the diagnosis and control of hypertension. Home BP is also an excellent predictive factor for the development of stroke (Citation20). In addition, it is a predictive factor for the development of stroke in patients on antihypertensive drug treatment (Citation21) and the incidence of stroke is higher when both the morning and evening BP values are high (Citation22). This study demonstrated that cilnidipine treatment caused a decrease in both morning and evening home BP, a finding favorable for BP control in post-stroke hypertensive patients. In this study, “normotensive” patients classified by clinic and home BP initially accounted for 11.9%. In the ACHIEVE-ONE study, the proportion of “normotensive” patients was 5.7% (Citation5). In the present study, the proportion of “normotensive” patients increased to 40.5% at 4 months of cilnidipine treatment; the corresponding rate was 35.9% at 3 months of treatment in the ACHIEVE-ONE study (Citation5). This indicates that cilnidipine treatment achieves almost equal BP control in post-stroke hypertensive patients. Patients with “sustained hypertension” accounted for 64.2%. Cilnidipine treatment decreased the proportion of this group of patients to 24.5% at 4 months, and to 18.7% at 12 months, indicating that the antihypertensive effect of cilnidipine occurred gradually and continued until after 12 months. Cilnidipine reportedly decreases morning BP in patients with riser-type hypertension, a causative factor of morning hypertension, through its sympathoinhibitory action via N-type calcium channel blockade (Citation6). Therefore, it is speculated that N-type calcium channel blockade was involved in the effect of cilnidipine in patients with morning hypertension observed in this study.
Target clinic BP values in the chronic phase of stroke are prescribed as <140/90 mmHg in the Japanese Guidelines for the Management of Stroke 2015, JSH2014, and the 2015 AHA/ASA secondary stroke prevention guidelines (Citation23). The 2013 ESH/ESC Guidelines for the management of arterial hypertension recommended clinic systolic BP values of <140 mmHg (Citation3). The VISP trial showed that controlling clinic BP to <140/90 mmHg in stroke patients over an observation period of 2 years reduced the risk of recurrence of stroke (Citation24). Cilnidipine treatment achieved BP values of <140/90 mmHg in 65.3% of the patients. In the NIPPON DATA, approximately 30% and 40% of Japanese men and women, respectively, who were on antihypertensive drug treatment had BP values of <140/90 mmHg (Citation25). In the J-HOME study (Citation26), 55.4% of 2281 Japanese hypertensive patients who were on antihypertensive drug treatment had BP values of <140/90 mmHg. Mori et al. (Citation27) reported that 31.7–40.7% of 2610 Japanese hypertensive patients who received CCB-based antihypertensive medications achieved BP values of <140/90 mmHg, while in diabetic hypertensive patients the target BP (<130/80 mmHg) was achieved in 11.3%. There were no marked differences between the results of these studies in Japanese hypertensive patients and the results of our study. However, the proportion of BP-controlled diabetic hypertensive patients in our study was higher than that in the study by Mori et al.
The target BP values are even lower according to the clinical subtype of stroke. According to JSH2014 (Citation2), in patients with cerebral hemorrhage, subarachnoid hemorrhage, or lacunar infarction, BP target values of <130/80 mmHg should be used if possible. The 2014 AHA/ASA secondary stroke prevention guidelines (Citation23) also state that it might be reasonable to target a systolic BP of <130 mmHg for patients with a recent lacunar stroke. In patients with small vessel occlusion, cilnidipine treatment increased the proportion of patients with BP values of <130/80 mmHg to 32.5%. Among patients with cerebral hemorrhage (hypertensive cerebral hemorrhage + other types of cerebral hemorrhage) and those with subarachnoid hemorrhage, the proportion of patients with BP values of <130/80 mmHg increased to 35.9% and 34.3%, respectively. In the present study, cilnidipine treatment improved the rate of achievement of target clinic BP regardless of the clinical subtype of stroke.
CKD is a risk factor for stroke (Citation28), and a meta-analysis found that the occurrence of stroke increased 1.43-fold when eGFR was <60 mL/min/1.73 m2 (Citation29). In this connection, we paid special attention to patients with an eGFR of <60 mL/min/1.73 m2. In patients who had been on other antihypertensive medications prior to cilnidipine treatment, the addition of cilnidipine to prior treatment increased the proportion of patients with clinic BP values of <140/90 mmHg. This indicates that cilnidipine treatment is also effective for BP control in post-stroke hypertensive patients with CKD.
In 815 elderly patients aged 75 years or older, the rate of achieving a target BP value of <150/90 mmHg was very high at 12 months of cilnidipine treatment. This suggests that strict BP control is feasible in elderly post-stroke hypertensive patients, who have a high risk of developing cardiovascular disease. JSH2014 recommends that the target BP be set individually in patients aged 75 years or older, according to their degree of frailty, but states that more aggressive BP control (<140/90 mmHg) may further improve the outcome if the treatment is well tolerated. Of 402 patients who had been on other antihypertensive medications prior to cilnidipine treatment, 26.6% had clinic BP values of <140/90 mmHg, but the corresponding proportion improved to 60.1% at 12 months of cilnidipine treatment. Thus, cilnidipine treatment was judged to be effective for post-stroke elderly hypertensive patients aged 75 years or older.
Although there are no established optimal BP values for the prevention of stroke recurrence, there are some reports that further BP reduction exerted beneficial effects in terms of inhibition of stroke recurrence, development of cerebral hemorrhage, and cardiovascular events. In the SPS3 study, an interventional trial of antihypertensive medications in patients with chronic lacunar infarction, there was no significant difference in the rate of recurrence of cerebral infarction between a group of patients with systolic BP values of <130 mmHg (achieved BP 127 mmHg) and another group with systolic BP values of 130–140 mmHg (achieved BP 138 mmHg), but the incidence of cerebral hemorrhage was significantly lower in the former group (Citation30). A subanalysis of the PROGRESS study revealed a lower rate of stroke recurrence with a stricter target (systolic BP of about 120 mmHg) (Citation31).
Antihypertensive treatment in post-stroke patients is aimed at preventing not only the recurrence of stroke, but also the development of new cardiac events. Intervention with antihypertensive medications was previously reported to inhibit both the recurrence of stroke and the development of cardiac events (Citation32). On the other hand, there is concern about the occurrence of adverse events associated with BP lowering. The SPRINT study demonstrated that the incidence of primary endpoints (cardiovascular outcomes and death) was lower in patients with systolic BP < 120 mmHg (achieved BP, 121.5 mmHg) than in those with systolic BP in the range 135–139 mmHg (achieved BP, 136.4 mmHg), but the incidence of adverse reactions to antihypertensive treatment was significantly higher in the former group (Citation33). In the present study, the target systolic BP of <130 mmHg was reached in 37.8% of the patients, and the target systolic BP of <120 mmHg in 14.6%. The incidence of adverse events attributable to excessive lowering of BP was 0.4% (12 of 2667 patients). There is another report that 32% of elderly persons aged 65 years or older have a fall at least once a year (Citation34). A meta-analysis of observational studies in the general population aged 60 years or older pointed out that the use of antihypertensive medication increases the risk of fall (Citation35), and an observational study in a general population of 3544 elderly persons with a median age of 70 years found that the risk of fall increases when the achieved BP value is low (Citation36). On the other hand, among elderly persons, hip fracture is caused by falling in about 80% of cases (Citation37), and an observational study in a general population of 301591 elderly persons with a mean age of 81 years has shown that the risk of hip fracture increased in the initial phase of antihypertensive treatment (Citation38). Among 815 patients aged 75 years or older in the present study, fall and hip fracture each occurred as adverse events in 1 (0.1%) patient. A one-year observational study of a general population of 7654 elderly persons with a mean age of 85 years has reported that hip fracture occurred at a frequency of 12.6/1000 person-years (Citation39). RCTs of cilnidipine treatment in hypertensive patients aged over 75 years will be needed to clarify the relationship between the target level of BP control achieved and the occurrence of adverse events.
Limitations of the study
This PMS study had no control group. Therefore, relative evaluation of the efficacy and safety of cilnidipine was not possible, despite the large number of patients enrolled. Regression to the mean and the Poisson effect might have been involved in the apparent antihypertensive effect of cilnidipine. Data of home BP might have included transcription errors and report bias, because home BP was measured by patients themselves. Since no target home BP was set up, it is also possible that there was bias due to the policies of physicians with respect to BP control. The study plan did not include the collection of BP data at the time of adverse events; therefore, it was not possible to examine the relationship between the adverse events and BP values. Although adverse events were collected according to the GPSP, cases of fall and fracture were not fully collected by calling for particular attention, for instance, by means of questionnaires. Therefore, the number of these cases might have been underestimated. In addition, it is also possible that biases due to medical institutions were involved. However, the medical institutions that participated in this study were distributed practically all over Japan (46 out of 47 prefectures), showing no predominance in particular regions. Thus, we believe that the results of this study well reflect the actual conditions regarding the treatment of post-stroke hypertensive patients in a real-world clinical setting.
In conclusion, the results of CA-ATTEND, a large-scale prospective PMS study, demonstrate that cilnidipine treatment was effective against uncontrolled BP and well tolerated in Japanese post-stroke hypertensive patients under real-world clinical setting. In addition, these results will assist in the generalization of the findings from RCTs in the routine clinical practice of Japanese stroke patients.
Declaration of interest
Masayasu Matsumoto and Naohisa Hosomi received scholarship donations from Mochida Pharmaceutical Co., Ltd. Naohisa Hosomi received an honorarium as a medical professional in this PMS study. Tsukasa Teshima and Hitoshi Sugii are employee of Mochida Pharmaceutical Co., Ltd. Shinobu Nagahama and Yoshiki Kurose are employee of EA Pharma Co., Ltd.
Acknowledgments
Data were analyzed by Ajinomoto Pharmaceuticals Co., Ltd. under the guidance of medical professionals, Masayasu Matsumoto and Naohisa Hosomi. We express their sincere gratitude to the 356 participating medical institutions and the 473 physicians who provided valuable data.
Funding
The present study was funded by Ajinomoto Pharmaceuticals Co., Ltd. and Mochida Pharmaceutical Co., Ltd. The name of Ajinomoto Pharmaceuticals Co., Ltd. was changed to EA Pharma Co., LTD since April 2016.
Additional information
Funding
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