The effects of missed doses of amlodipine and losartan on blood pressure in older hypertensive patients

Abstract

This randomized, double-blind, parallel-group, multicenter study compared the efficacy of amlodipine and losartan in an older hypertensive population, focusing on therapeutic coverage in the case of missed doses. Following a 4-week, single-blind, placebo washout period, 211 patients were randomly assigned to receive either 5 mg of amlodipine once daily or 50 mg of losartan once daily. Doses were doubled after 6 weeks of treatment if the diastolic blood pressure exceeded 90 mm Hg. After the 12-week treatment period, patients received the placebo for 2 days (drug holiday) to simulate two missed doses of antihypertensive medication. Twenty-four-hour ambulatory blood pressure monitoring was conducted at the end of the placebo washout period (baseline), upon completion of the 12-week treatment period (steady state), and after the 2-day drug holiday. Amlodipine was more effective than losartan in reducing patients' 24-h ambulatory blood pressure at the steady-state sampling time. The increases in 24-h blood pressure during the drug holiday averaged 6±2/2±1 mm Hg (P<0.0001) in the amlodipine group and 3±2/2±1 mm Hg (P<0.0001) in the losartan group. The rise in systolic pressure was greater in patients on amlodipine than in those on losartan (P<0.0001). For diastolic pressure, the changes did not differ. Owing to the lower pressure during treatment, patients in the amlodipine group remained at a significantly lower blood pressure level after the 2-day drug holiday. Amlodipine was more effective than losartan in lowering blood pressure and in maintaining blood pressure control after two missed doses, and the difference was most significant for systolic blood pressure.

Predictors of poor medication adherence of older people with hypertension

“…Similarly, participants without falls due to physical discomfort in the last 6 months were more likely to have good medication adherence than those with falls. This finding was consistent with that reported by Berry et al (Berry et al., 2010 ), which showed an increased risk of falls in people with poor medication adherence, possibly because the risk of falls increased with a gradual rise in blood pressure resulting from poor medication adherence (de Leeuw et al., 2017 ). Few studies have indicated a higher risk of falls at the start of pharmacotherapy (Butt et al., 2012 , 2013 ; Shimbo et al., 2016 ).…”

Association between gaps in antihypertensive medication adherence and injurious falls in older community-dwelling adults: a prospective cohort study

“…A number of observational studies have consistently identified a higher risk of falling following antihypertensive medication initiation or titration 7–12. Patients with poor medication adherence, specifically poor implementation of antihypertensive pharmacotherapy, characterised by gaps in antihypertensive medication use, may experience a gradual rise in blood pressure 27–29. On resumption of therapy, similar to initial use, patients may be at a greater risk for falls relative to those who do not have gaps in antihypertensive therapy.…”

“…Participants’ blood pressure during the follow-up period was not measured to assess fluctuations in blood pressure. However, the ability of antihypertensive drugs to lower blood pressure have been proven in clinical trials,1–3 and clinical studies have shown that withdrawal of these medications leads to a gradual rebound in blood pressure 27–29. Furthermore, the feasibility of undertaking these measurements, which would likely require daily measurements, is unlikely in large observational studies such as this.…”

“…Pharmacy dispensing records are an objective and indirect measure of medication adherence 35 36. We chose a 5-day gap based on the literature describing the gradual decline of the antihypertensive medication effect on blood pressure over 3 days,27–29 extending this period to 5 days due to the indirect method of adherence measurement, and to allow for potential variation in antihypertensive medication pharmacology 37. The number of occasions when gaps of 5 days occurred between sequential supplies during the previous 12 months was evaluated at baseline.…”

“…The quality of implementation of a medication regimen should be interpreted according to the pharmacology of the drug. During gaps in antihypertensive medication use, the pharmacological effects on blood pressure gradually diminish,27–29 and on resumption of therapy, patients may experience acute changes to blood pressure similar to initial use.…”