Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two ‘missed doses’: a randomised, double-blind comparative trial in Asian patients

Abstract

Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-tomoderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n ¼ 109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n ¼ 113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4 7 7.0 vs 11.2 7 11.3 mmHg for systolic BP (Pp0.0001) and 2.4 7 6.3 vs 6.0 7 6.0 mmHg for diastolic BP (Pp0.0002). Significant differences between the two drugs in mean 24-h ambulatory BP levels were already evident on day 1 after withdrawal, even though there were no significant differences on the final day of treatment. No differences in safety parameters were observed, and neither drug caused any serious or severe treatment-related adverse events. In conclusion, amlodipine provides greater protection than nifedipine GITS against loss of BP control following missed doses.

A randomized controlled trial on the blood pressure–lowering effect of amlodipine and nifedipine‐GITS in sustained hypertension

“…The difference became significant beyond 24 hours of drug ingestion. These findings are in keeping with the results of three previous studies of similar design in clinic hypertension …”

“…Taken the results of these previous studies and our present study together, amlodipine but not nifedipine‐GITS may maintain its blood pressure–lowering effect after having missed one or two doses of medication. This pharmacologic difference may have clinical implications when a patient's drug adherence is low.…”

“…The corresponding values for nifedipine‐GITS were 14% and 16%, respectively. In a later and larger study in Asians (n = 222), similar results were observed . The mean ambulatory blood pressure rise (±standard deviation) during the last 9 hours on day two after having missed a dose was significantly less with amlodipine than with nifedipine‐GITS (4.4 ± 7.0 vs 11.2 ± 11.3 mm Hg for systolic blood pressure and 2.4 ± 6.3 mm Hg vs 6.0 ± 6.0 mm Hg for diastolic blood pressure, P ≤ 0.0002).…”

“…In the class of dihydropyridine calcium channel blockers, amlodipine is a long‐acting compound because of its more than 50 hours of long half‐life time, and nifedipine gastrointestinal therapeutic system (GITS) uses a controlled‐release technique . Several previous studies compared the 24‐hour blood pressure–lowering effect of these two drugs, but produced inconsistent results . One but not the other studies demonstrated that amlodipine was more efficacious than nifedipine‐GITS in blood pressure lowering, especially during the trough hours in the morning or after having missed one or two doses of medication.…”

Amlodipine as an antiischemic drug is superior to long acting nitrates

“…Because of some characteristics such as concentration-time profiles and duration of action, amlodipine can provide better therapeutic coverage than other drugs that have a shorter duration of action. As it has been mentioned, the antihypertensive efficacy of amlodipine persists after 2 „missed doses“ [50, 51]. There is no recorded evidence of tolerance to amlodipine over 3 months, and any significant problem associated with its withdrawal [52].…”