Inhibitory Effects of Azelnidipine Tablets on Morn

Authors: Kazuomi Kario Yuki Sato Masayuki Shirayama Megumi Takahashi Kazuhito Shiosakai Katsutoshi Hiramatsu Masahiro Komiya Kazuyuki Shimada

Publish Date: 2013/03/20

Volume: 13, Issue: 1, Pages: 63-73

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Abstract

Morning hypertension is a risk factor for cardiovascular and cerebrovascular events Furthermore it is a useful measure for definitive diagnosis of hypertension and patients who selfassess their own blood pressure BP in the morning tend to exhibit better compliance with antihypertensive medication than those who do notWe conducted the Azelnidipine Treatment for Hypertension Openlabel Monitoring in the Early morning AtHOME Study by surveying patients who were taking azelnidipine According to the study protocol high systolic BP SBP was defined as ≥135 mmHg when measured at home in the morning and ≥140 mmHg when measured at the clinic during the day A total of 5433 hypertensive patients who were registered at 1011 medical institutions across Japan were enrolled in the study Data obtained from 4852 of these patients mean age 648 years female 529  previous medication with other antihypertensive agents used concomitantly with the present study agent 455  were used for efficacy analysisAt baseline the subjects’ mean ± standard deviation SBP/diastolic BP values at home in the morning at the clinic during the day and at home in the evening were 1569 ± 164/897 ± 120 1575 ± 187/891 ± 133 and 1502 ± 176/856 ± 122 mmHg respectively The mean pulse rates were 727 ± 107 749 ± 112 and 725 ± 96 beats/min respectively Patients whose BP was defined as high accounted for 834  of the study population whereas 99  had ‘masked’ hypertension defined as SBP of ≥135 mmHg at home in the morning and 140 mmHg at the clinic However from 4 weeks after initiation of azelnidipine treatment till the end of the study at week 16 all three daily BP determinations were significantly p  00001 lowered and pulse rates at home in the morning at the clinic and at home in the evening were similarly and significantly reduced by −37 ± 80 −35 ± 95 and −35 ± 73 beats/min respectively Whereas achievement of home SBP of 135 mmHg in the morning was noted in only 66  of patients before the start of azelnidipine treatment this was noted in 433  after 16 weeks Meanwhile achievement of clinic SBP of 140 mmHg was increased from 129  of patients to 561  of patients at the same timepoints After azelnidipine treatment 322  of patients had wellcontrolled hypertension in both the home and clinic settings Adverse drug reactions occurred in 292  of patients 154/5265 All adverse drug reactions were as expected for the calcium antagonist class of agentsMorning hypertension and morning blood pressure BP surge are serious risk factors affecting cerebrovascular and cardiovascular events and controlling them is expected to greatly improve the prognosis of patients with hypertension 1 It was reported in the Jichi MorningHypertension Research JMORE Pilot Study performed in patients treated with antihypertensive drugs in Japan that more than half of the patients who had wellcontrolled BP when it was measured at the clinic during the day clinic BP suffered from morning hypertension and their BP measured at home in the morning morning home BP was poorly controlled 2 Pickering et al 3 compared normotension with masked hypertension and warned that the latter would increase the relative risk of cardiovascular events to an extent comparable with or higher than that of sustained hypertension An epidemiological study performed in residents of Ohasama Machi in Iwate Prefecture Japan also found that morning home BP was a better predictor of cardiovascular disease or death than clinic BP 4 suggesting that measurement and control of morning home BP is very important for effective antihypertensive therapy Measurement of BP at home is also useful for achieving better treatment compliance and for evaluating the effectiveness of antihypertensive drugs and morning measurement before intake of medication in particular has been reported to be useful for the evaluation of sustained BPlowering effects of antihypertensive drugs administered once daily 5 Thus more significant clinical findings from evaluation of antihypertensive drug efficacy would be expected using morning home BP as an index rather than using clinic BPAzelnidipine is a dihydropyridine calcium antagonist which was synthesized by Ube Industries Ltd and developed by Sankyo Co Ltd now known as Daiichi Sankyo Co Ltd Tokyo Japan This agent has a potent and sustained BPlowering effect in various animal models of hypertension 6 It has also been confirmed to have renoprotective effects such as reducing proteinuria by dilating efferent arterioles as well as cardioprotective insulin resistanceimproving cerebroprotective and antiatherosclerotic effects 7 8 In a comparative clinical study using the index of 24h ambulatory BP monitoring azelnidipine with lipophilicity 17fold higher than that of amlodipine showed a sustained 24h BPlowering effect comparable to that of amlodipine 9 Meanwhile azelnidipine had no effect on pulse rates unlike amlodipine and had a mildly suppressive effect rather than an inductive effect on reflective tachycardia in response to hypotension 10 These properties are thought to arise because azelnidipine hardly activates the sympathetic nervous system

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