Ambulatory Blood Pressure Control: Azelnidipine or Amlodipine?

When it comes to the very first step of management of hypertension, Ambulatory Blood Pressure (ABP) is considered to be a better tool for measuring hypertension. It tends to overcome phenomenon such as White- coat effects, as well as masked hypertensions and studies, have also shown that ABP monitoring is superior to clinic BP monitoring in predicting cardiovascular events (1).

Ambulatory BP is generally measured by 24-hour monitoring using a device and since the BP is monitored over a period of 24-hour, it encompasses the points of morning BP, office BP as well as nighttime BP thus providing more holistic estimates of hypertension. This further helps in reducing the number of possible false readings, along with the added benefit of understanding the dynamic variability of BP.(2,13) Ambulatory Blood Pressure Monitoring (ABPM) can further detect circadian changes (diurnal rhythmic changes, including nocturnal dipping and morning surge) and BP variation with different environmental and emotional changes(3)

Because of these benefits, medical bodies worldwide including USPSTF in North America (4), NICE in the UK (5), Japanese Society of Hypertension (6) and many more (7) after carefully examining the evidence as to which method of BP measurement is best—office BP, home BP, or ABPM—have unanimously recommended ABPM as the "gold standard" technology for BP measurement. Even in 2018, the ACC/AHA hypertension management guidelines recommended ABPM for out‐of‐office measurement in clinical practice. (8)

Calcium channel blockers are a popular medium in the treatment of hypertension and control of Ambulatory BP in particular, primarily due to the fact that these drugs are known to have a reliable hypotensive effect with few adverse reactions and are have both cardiovascular and cerebrovascular benefits. Even in these, long-acting calcium antagonists is generally recommended over the short-term counterparts (9)

Comparison of Amlodipine and Azelnidipine on Ambulatory BP

Amlodipine and Azelnidipine are two of the common calcium channel blockers used in the management of hypertension. Azelnidipine, a new calcium antagonist, differs from amlodipine with respect to its pharmacokinetic profile.

Because Azelnidipine is highly lipid-soluble (10), it is retained in the vascular wall after clearance from the blood and continues to elicit a hypotensive effect (11)

The Study and Methodology

The comparison of these two popular formulations on their impact on Ambulatory BP was the subject or research conducted by Kuramoto K, Ichikawa S et al (12) in their article Azelnidipine and Amlodipine: a Comparison of Their Pharmacokinetics and Effects on Ambulatory Blood Pressure - where the researchers aimed to compare the effects of azelnidipine and amlodipine on 24-h blood pressure;

Further, they also targeted to monitor the plasma concentration vs. the time profile in order to assess the association between pharmacokinetics and hypotensive activity after administration of either drug for 6 weeks.

For the purpose of the study, Blood pressure and pulse rate were measured by 24-h monitoring with a portable automatic monitor in a randomized double-blind study of 46 patients with essential hypertension.

Azelnidipine 16 mg (23 patients) or amlodipine 5 mg (23 patients) was administered once daily for 6 weeks. Pharmacokinetics were analyzed after the last dose was taken.

Results

The researchers found that both drugs showed similar effects on the office blood pressure and pulse rate. During 24-h monitoring, both drugs caused a decrease in systolic blood pressure of 13 mmHg and had a similar hypotensive profile during the daytime period (07:00–21:30).

The pulse rate decreased by 2 beats/min in the azelnidipine group, whereas it significantly increased by 4 beats/min in the amlodipine group.

Similar trends in the blood pressure and pulse rate were observed during the nighttime (22:00–6:30) and over 24 h. Excessive blood pressure reduction during the nighttime was not seen in either group.

The pharmacokinetic results indicated that the plasma half-life (t1/2) of amlodipine was 38.5±19.8 h and that of azelnidipine was 8.68±1.33 h. Despite this difference in pharmacokinetics, the hypotensive effects of amlodipine and azelnidipine were similar throughout the 24-h administration period.

Conclusion

In this study, 24-h monitoring of the blood pressure and pulse rate with a portable automatic monitor demonstrated that both drugs had a stable hypotensive effect lasting for at least 24 h after administration. The authors made note the similar impact of amlodipine and azelnidipine on ambulatory BP while also noting the fact that while pulse rate decreased with administration of azelnidipine, it significantly increased with administration of amlodipine

References

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5) National Institute for Health and Clinical Excellence (NICE). The Clinical Management of Primary Hypertension in Adults. London, UK: National Institute for Health and Clinical Excellence; 2011.

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8) Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71:e127‐e248.

9) Alderman MH, Cohen H, Roque R, et al: Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hypertensive patients. Lancet 1997; 349: 594–598

10) Yoram Y, Ahuva L: Azelnidipine (CS-905), a novel dihydropyridine calcium channel blocker with gradual onset and prolonged duration of action. Cardiovasc Drug Rev 1995; 13: 137–148.

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12) Kuramoto K, Ichikawa S, et al, Azelnidipine and Amlodipine: a Comparison of Their Pharmacokinetics and Effects on Ambulatory Blood Pressure (Hypertens Res 2003; 26: 201–208)

13) Dadlani A, Madan K, Sawhney JPS. Ambulatory blood pressure monitoring in clinical practice. Indian Heart J. 2019;71(1):91‐97. doi:10.1016/j.ihj.2018.11.015  

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