Controlling Morning Hypertension with Azelnidipine

Control of morning hypertension is often a significant challenge for patients and treating physicians alike. Morning hypertension, simply defined as high Blood pressure in the morning is known to have significant cardiovascular as well as cerebrovascular implications including those of ischemic stroke and adverse coronary events.

Moreover, measurement of morning BP is considered to be a better indicator of hypertension in general and patients who self-assess their own blood pressure (BP) in the morning tend to exhibit better compliance with antihypertensive medication than those who do not. With this background, control of morning hypertension is one of the first targets of physicians in their strategy to control overall hypertension and improve the CVD health of their patients

Calcium channel blockers are one of the most common arsenals in the armour of medical practitioners in controlling hypertension. Further newer generation calcium channel blockers (CCB) are known to have a reliable hypotensive effect with few adverse reactions.

Understanding Azelnidipine

Azelnidpine is one such calcium antagonist that was first developed by Ube Industries, Ltd. (Yamaguchi, Japan) and Sankyo Co., Ltd. (Tokyo, Japan). Regarded as the third generation of CCB also reported having better renoprotective effects such as reducing proteinuria by dilating efferent arterioles (2). Studies have also confirmed the drug to be cardioprotective, insulin resistance-improving, cereboprotective and having anti-atherosclerotic effects.

Further, this new calcium antagonist is highly lipid-soluble (3), it is retained in the vascular wall after clearance from the blood. Studies have shown that Azelnidipine has 17 times higher lipophilicity as compared to Amlodipine and showed a sustained 24-h BP-lowering effect comparable to that of amlodipine (4)

Azelnidipine and Morning Hypertension

The effect of Azelnidipine on morning hypertension was the focus of a study performed by Kario K, Sato Y, Shirayama M, et al and published in Drugs R D (2013) where the authors aimed to determine the BP- and pulse rate-lowering effects of azelnidipine, a long-acting dihydropyridine calcium antagonist administered once daily in the morning.

For the same, the authors performed the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) 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.

Methodology

A total of 5,433 hypertensive patients, who were registered at 1,011 medical institutions across Japan, were enrolled in the study. Data obtained from 4,852 of these patients (mean age, 64.8 years; female, 52.9 %; previous medication with other antihypertensive agents used concomitantly with the present study agent, 45.5 %) were used for efficacy analysis.

At the 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 156.9 ± 16.4/89.7 ± 12.0, 157.5 ± 18.7/89.1 ± 13.3, and 150.2 ± 17.6/85.6 ± 12.2 mmHg, respectively. The mean pulse rates were 72.7 ± 10.7, 74.9 ± 11.2, and 72.5 ± 9.6 beats/min, respectively. Patients whose BP was defined as high accounted for 83.4 % of the study population, whereas 9.9 % had 'masked' hypertension, defined as SBP of ≥135 mmHg at home in the morning and <140 mmHg at the clinic.

Results

The study results showed that 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 < 0.0001) lowered, and pulse rates at home in the morning, at the clinic, and at home in the evening were similarly and significantly reduced (by -3.7 ± 8.0, -3.5 ± 9.5, and -3.5 ± 7.3 beats/min, respectively). Other results of the study included

• Whereas achievement of home SBP of <135 mmHg in the morning was noted in only 6.6 % of patients before the start of azelnidipine treatment, this was noted in 43.3 % after 16 weeks.

• Achievement of clinic SBP of <140 mmHg was increased from 12.9 % of patients to 56.1 % of patients at the same time points.

• After azelnidipine treatment, 32.2 % of patients had well-controlled hypertension in both the home and clinic settings.

• Adverse drug reactions occurred in 2.92 % of patients (154/5,265). All adverse drug reactions were as expected for the calcium antagonist class of agents.

Conclusion

With these results the authors found azelnidipine to be one of the most useful antihypertensive drugs because of its reliable and persistent BP-lowering effects. Furthermore, azelnidipine reduced pulse rates significantly, the authors further concluded.

References

1. Kario K, Sato Y, Shirayama M, et al. Inhibitory effects of azelnidipine tablets on morning hypertension. Drugs R D. 2013;13(1):63–73.

2. Abe H, Mita T, et al. Comparison of effects of cilnidipine and azelnidipine on blood pressure, heart rate and albuminuria in type 2 diabetics with hypertension: A pilot study Journal of Diabetes Investigation Volume 4 Issue 2 March 2013 , doi: 10.1111/jdi.12003, 2013

3. Oizumi K, Nishino H, Koike H, et al: Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker. Jpn J Pharmacol 1989; 51: 57–64.

4. Kuramoto K, Ichikawa S, Kirai A, et al. Azelnidipine and Amlodipine: A comparison od their pharmacokinetics and effects on ambulatory blood pressure 

The following article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Azelnidipine, click here