Debate on best time to take Antihypertensive medication

Many of us came across the European journal publication recommending that administration of antihypertensive medication at night is more effective. The research showed that group of participants who took blood pressure medication at night had a 43% lower risk of cardiovascular disease.This is known that Blood presssure exhibits a circadian variability. Ambulatory Blood Pressure monitoring (ABPM) were found to show this diurnal rhythm. This remains the only method to identify nocturnal dipping or non-dipping. A drop in Blood pressure in the evening and through night is a normal physiological phenomenon. Blood pressure starts declining from late evening and reaches its lowest at midnight and shoots up just after awakening. Nocturnal non-dipping is currently regarded as a predictor of CV risk factor and target organ damage. In healthy subject there is 10-15% lower values of systolic BP recorded at night (nocturnal dipping). With ageing there is gradual shift of systolic BP to stay raised during the night and therefore increased risk of CV events. Cardio vascular risk associated with non-dipping BP profile includes; left ventricular hypertrophy, increased proteinuria, secondary form of hypertension, increased insulin resistance and increased fibrinogen level.Due to known association of nocturnal raised BP to CV risks, in European research antihypertensive therapy has been aimed at reducing night time BP. This study also recommends to arrange a 24 hour BP measurement to get better insight into a patient’s risk of CVD.

Let’s have a look at most commonly prescribed antihypertensive drugs and their duration of action.

Name of the drug Normal dosing Peak plasma level (average) Elimination half life

Ramipril (ACE inh). Once daily (am) 3 Hr. 15 Hr

Amlodipine (CCB). Once daily (am) 9 Hr 35 Hr

Bendroflumethiazide (Diuretic) (am) 2 Hr 5 Hr

Losartan (ARB II ant) Once daily (am) 2 Hr 5 Hr

With slight variability due to patient factors such as hepatic or renal insufficiency, it is clear that most of well-known antihypertensives would have near diminished amount circulating at night following one dose in the morning. In light of several studies suggesting that targeting the raised BP through the night, it may become a good practice to suggest that once daily antihypertensive medication are better taken in the evening (with exception of diuretics for obvious reasons).

Despite many published studies there is no current recommendation to endorse the above statement. All patients, however, should not be asked to start changing the timing of their medication. A patient with confirmed non-dipping (via ABPM) will make a good candidate of altering the time of antihypertensive medication.

British Heart Foundation has set a grant of £1 Million towards this study to be replicated in UK. The aim is to recruit 10’000 patients from various demographic backgrounds. They will be studied over a period of 5 years. Patients who take a medication for Blood pressure that has a twice daily dosing and those who work night-shift will not be able to participate.

We look forward to the results of the study in UK and its interpretation into clinical practise.