Is the blood pressure lowering effect of dihydropyridine calcium channel blockers consistent or variable throughout 24 hours?

Background

High blood pressure, also known as hypertension, is a risk factor for adverse cardiovascular events such as stroke and heart attack. Blood pressure varies widely in an individual but certain patterns in its rise and fall have been identified in the general population; blood pressure increases in the early morning hours and decreases during the night. There is a variety of treatment options available for treating high blood pressure. Dihydropyridine calcium channel blockers are a group of drugs used to lower blood pressure.

Study characteristics

This review explores whether the blood pressure lowering effect of dihydropyridine calcium channel blockers in adults (aged 18 years or over) with high blood pressure (systolic blood pressure (the upper blood pressure reading) of at least 140 mmHg or diastolic blood pressure (the lower blood pressure reading) of at least 90 mmHg, or both of these) is consistent or variable over a 24-hour period. We performed a review of studies that compared the 24-hour blood pressure lowering effects of six of these drugs versus a control treatment for at least three weeks. Blood pressure needed to be measured by an ambulatory blood pressure monitor, which is a device that automatically measures blood pressure at regular intervals. We performed searches for clinical trials up to February 2014.

Key results

We found 16 trials involving 2768 participants that studied five drugs given once a day (amlodipine, lercanidipine, mandipine, nifedipine, and felodipine) and one drug given twice a day (nicardipine). The amount of blood pressure lowering by dihydropyridine calcium channel blockers stayed relatively the same at every hour throughout a 24-hour day. The average hourly differences in blood pressure were between 9.45 mmHg and 13.2 mmHg for systolic blood pressure and between 5.85 mmHg and 8.5 mmHg for diastolic blood pressure. At the present time, the benefits and harms of this pattern of blood pressure lowering are unknown.

Quality of the evidence

We judged the overall quality of the evidence to be moderate. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Authors' conclusions: 

Six dihydropyridine calcium channel blockers studied in this review lowered blood pressure by a relatively similar amount each hour over the course of 24 hours. The benefits and harms of this pattern of blood pressure lowering are unknown. Further trials are needed with accurate recording of time of drug intake and with reporting of standard deviation of blood pressure at each hour. We did not attempt to assess adverse effects in this review due to the lack of reporting and the short duration of follow-up.

Read the full abstract...
Background: 

Calcium channel blockers are a heterogeneous class of drugs, including dihydropyridine and non-dihydropyridine subgroups, commonly used in the treatment of hypertension. A systematic review of the 24-hour time course of the blood pressure-lowering effect has not been published.

Objectives: 

To assess how much variation there is in hourly systolic and diastolic blood pressure lowering by dihydropyridine calcium channel blockers over a 24-hour period in people with hypertension aged 18 years or over, with baseline systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg, or both.

Search strategy: 

We performed electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2014), MEDLINE (1946 to February 2014), EMBASE (1974 to February 2014), and ClinicalTrials.gov (to February 2014). We also screened references of published studies and reviews to identify additional trials.

Selection criteria: 

We included all randomized, placebo-controlled trials assessing the hourly effects of dihydropyridine calcium channel blockers by ambulatory blood pressure monitoring in adults with hypertension with a follow-up of at least three weeks.

Data collection and analysis: 

Two authors independently selected the included trials, evaluated the risk of bias, and analyzed the data.

Main results: 

We included 16 randomized controlled trials of dihydropyridine calcium channel blockers in this systematic review, with 2768 randomized participants. Drugs studied included amlodipine, lercanidipine, mandipine, nifedipine, and felodipine (all administered once daily) and nicardipine (administered twice daily). We analyzed and presented data by hour post dose. The blood pressure-lowering effect was stable over time; there were no clinically important differences in blood pressure-lowering effect of calcium channel blockers between each hour for either systolic blood pressure (estimated mean hourly differences ranged between 9.45 mmHg and 13.2 mmHg) or diastolic blood pressure (estimated mean hourly differences ranged between 5.85 mmHg and 8.5 mmHg). However, there was a moderate risk of bias for this finding. Once-daily dihydropyridine calcium channel blockers appeared to lower blood pressure by a relatively constant amount throughout the 24-hour dosing interval.

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