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Resistant hypertension: what to do after ACD

Dr Ivan Benett and Dr Kathryn Griffith on how to manage a patient whose BP remains high despite being on three antihypertensives.

Joel is 59 years old and was born in Kingston, Jamaica, but has lived in the UK for 43 years. He has been active all his life. Ten years ago he was diagnosed with diabetes and soon after started treatment for hypertension. He has always resented being labelled as ‘diabetic' but worries about high blood pressure. He remains physically active and continues to play for the local veterans cricket team, bowling rather slower than he did 30 years ago. He enjoys life.

At his recent annual review he had no diabetic complications and his glycaemic control and renal function were both good. There was no microalbuminuria, but his blood pressure was still too high – remaining stubbornly over 160/100mmHg. He is being prescribed simvastatin, ramipril, amlodipine and a thiazide to optimal doses.

What more can be done to reduce his blood pressure without further medication?

Ensure that readings are being done under ideal conditions. If blood pressure is still high in the office, try home monitoring, remembering that home blood pressure is lower than office blood pressure.1

Reinforce lifestyle modification, check smoking status and ask about alcohol intake. Review his diet, as it is important for him to have a reduced fat and salt intake. For example, although he may not add salt to his food, foods like salt fish or jerk chicken are very salty. If necessary, consult a dietician who is familiar with ethnic-minority diets, to find out what to ask about – or even refer him to one with a special knowledge of Caribbean food. A diet rich in fruit and vegetables, with low-fat dairy products and reduced saturated and total fat, significantly reduces blood pressure.2 The Dietary Approaches to Stop Hypertension (DASH) diet is even more effective if combined with weight loss and exercise.3

Check adherence to his medication by asking him whether he takes his treatment regularly, and also check whether this is consistent with repeat prescription requests. Many factors can interfere with adherence to medication.4

Encourage concordance. Assess his understanding of blood pressure and its effects, exploring his fears, ideas, concerns and expectations.5 Ask explicitly about worries over potential side-effects, including erectile dysfunction and any other ‘taboo' subjects. Provide literature on hypertension and treatments, such as a standard patient information leaflet, making sure it is written in a way he will understand.

Suggestions for improving concordance include:6

• involving the patient in making treatment decisions

• increasing the patient's knowledge about regimens and the rationale for treatment

• providing patient counselling and information leaflets

• using single-daily or (if not available) twice-daily dosing

• using combination tablets

• minimising polypharmacy

• using compliance aids when appropriate (such as a dosette box)

• considering side-effects that may cause discontinuation of drug use and, as appropriate, changing the regimen.

Review aggravating factors such as prescribed, over-the-counter or recreational drugs. Ask specifically about NSAIDs as he may be taking them, unaware that they interact with ACE inhibitors. Consider alcohol binge-drinking.

What further investigations are needed?

Review the investigations already performed including pre-treatment electrolytes, urine for blood and albuminuria. Check for any decline in renal function greater than 5ml/min/1.73m2 in a year, or 10ml/min/1.73m2 in five years,7 remembering to factor the reported eGFR by 1.21 as he is of African origin. Consider referral for renal ultrasound if there is decline in renal function greater than above, macroscopic or persistent microscopic haematuria, or symptoms of renal outflow obstruction.

Other causes of secondary hypertension should be considered but remain unlikely, such as endocrine or anatomical causes. Pre-treatment hypokalaemia may indicate hyperaldosteronism or Cushing's syndrome.

What fourth-line drugs should be considered?

Referral to a GPSI or to secondary care could be made at this stage. However, fourth-line drugs may also be considered in the absence of an underlying cause for the resistance to current medication. These may include:

• Spironolactone. Hyperaldosteronism is present in about one in eight people with essential hypertension, so it may be worth considering a small dose of 25-50mg daily to assess response, reviewing serum K+ frequently.8

• Beta-blockers. It may be worth introducing one of these, particularly if there is evidence of raised sympathetic drive like a fast pulse rate.9 As a second-line intervention, ß-blockers reduce blood pressure by 6/4mmHg at standard doses, and 8/6mmHg at twice that dose.10

• Alpha-blockers. The blood pressure-lowering effect of a-blockers is modest at best and the estimates of 8/5mmHg may be overstated. There does not appear to be a significant difference between the various a-blockers. Trials are mainly of short duration and so long-term adverse effects cannot be quantified.11

• Moxonidine. This centrally acting drug has been shown in short-term, small studies to be as effective as other hypotensives at lowering blood pressure. However, evidence is limited on long-term benefit, tolerability and unwanted effects.

• Aliskiren. Both the beneficial effects and adverse effects of this drug are still to be fully assessed. In some areas this drug can only be prescribed in high-risk patients who are poorly controlled and cannot tolerate other conventional drugs.

• Methyldopa and hydralazine are other older drugs that may be considered, although evidence is limited on their efficacy and unwanted effects. These vasodilators may have theoretical benefits in people of African origin.12


Apparent resistance to medication is not uncommon. Consider fourth-line drugs only after exploring issues around concordance, and considering underlying causes of hypertension. Referral should be considered if blood pressure targets are still not achieved. Fourth-line drugs may sometimes help although they could also aggravate the risks of polypharmacy.

Dr Ivan Benett is GPSI in cardiology for NHS Manchester

Dr Kathryn Griffith is GP in York and hospital specialist at York Hospital Foundation Trust

Competing interests None declared

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