Resistant hypertension: definition and the five management steps

What it is

Resistant hypertension can be true or pseudo-resistant hypertension. True resistant HTN is blood pressure that remains above goal in spite of concurrent use of three or more antihypertensive agents of different classes in full or maximally tolerated doses. One of the three medications should be diuretics if tolerated and not contraindicated. Thus, patients whose blood pressure is controlled with four or more medications should be considered to have resistant hypertension. Note what that means: the label does not turn on the blood pressure being above goal today, it turns on how many agents are needed to hold it down. Pseudo-resistant hypertension is poorly controlled HTN that appears resistant to treatment but actually attributed to other factors.

Causes and risk

The prevalence of resistant HTN has been reported to range from 5-30 % of overall hypertensive population, with true resistant HTN representing less than 10% of this prevalence. So most of what looks resistant is not, and step two, which is to rule out pseudo-resistance, comes before the fourth drug of step four. Step two is to rule out the possibilities of pseudo-resistance and consider adequate management if any of the following is present:

1. Poor BP measurement technique.
2. Poor adherence to antihypertensive therapy because of side effect of medications, complicated dosing schedule, inadequate patients education, memory or psychiatric or vision problems.
3. Suboptimal antihypertensive therapy such as inadequate doses or inappropriate combinations or physician inertia (failure to change or increase dose of regimens when target BP is not achieved).
4. Poor adherence to lifestyle and dietary measures to lower blood pressure such as obesity, high-salt diet, physical inactivity, heavy alcohol intake, smoking and poor sleep hygiene.
5. Drugs and substances that can aggravate HTN.

Those drugs and substances are set out by class: ephedrine and pseudoephedrine hydrochloride in cough and cold medicines and in eye and nasal preparations; the corticosteroids prednisolone and hydrocortisone; the NSAIDs ibuprofen, diclofenac, mefenamic acid and celecoxib; estrogen with progesterone, in contraception and in replacement therapy; tricyclic antidepressants and fluoxetine; the immunosuppressants cyclosporine and tacrolimus; and the dietary supplements ginseng, natural licorice, yohimbine and caffeine. Physician inertia, the failure to change or increase the dose of regimens when target BP is not achieved, is a cause of pseudo-resistance in its own right, alongside the patient's adherence.