Hypertension

Primary hypertension

All newly seen patients with hypertension should have thought given to whether they might not have a secondary cause (see below). Just because somebody has been treated for the last few years does not mean that secondary hypertension has been excluded. Many problems of blood pressure control are related to poor adherence to treatment, and this needs to be thoroughly explored before adding yet more poorly tolerated medication to a failing regimen.

Measuring blood pressure

Basing life-long therapy on a single rushed reading in an anxious hungry patient is inappropriate. Patients should be rested, sitting with back support and feet on the ground, and not have smoked recently. The cuff should be at the level of the heart and should be the correct size.¹. This study showed that incorrect cuff size is fixable and a clear source of major error – using a regular cuff on a very large arm can give a value up to 20 mmHg higher than the correct reading, and using a regular cuff on a small arm under-reads by 4 mmHg.

If the arm is in the lap or hanging free (not supported on the desk), readings can be over-estimated by about 5 mmHg². Aim for more than one reading.

Treatment indications

Blood pressure warrants treatment in adults of any age if the diastolic >90; the current systolic cut-off is >140 .³ The target of treatment is values below these levels. The same values are the minimum used for patients with risk factors such as chronic kidney disease and diabetes, and the only additional recommendation is that an ACEI or ARB should be part of the treatment for those with CKD. More aggressive BP lowering for those with additional CVS risk was not recommended based on unproven efficacy of that approach. However the recent SPRINT trial has suggested a mortality advantage (NNT 270 per year) of a systolic target of 120 mmHg.⁴There are a number of issues about this trial (stopped early, elderly patients, published in a rush, but it is certainly food for thought: see under ‘perspective – how low should one go’ later in the text.)

The usual step care is:

Start with hyrdrochlorothiazide 12.5 mg daily. This is a ceiling diuretic, so pushing the dose to 25 mg when the dose response curve plateaus at 8 mg seldom results in much further response, although guidelines often recommend doses of 25 and even 50 mg because these were the doses used in the original trials.

Furosemide is NOT an appropriate alternative other than in patients with associated cardiac or renal failure. In the latter, however, the attainment of blood pressure control does require an adequate dose of a loop diuretic and this should be the first change made in a failing regimen in a patient with renal impairment

Chlorthalidone or hydrochlorothiazide as preferred diuretic in hypertension

The second agent can be either an ACE inhibitor or a calcium antagonist. Preference should be given to available agents that can be dosed once daily – e.g. amlodipine 5 mg then 10 mg. Fluid retention with the calcium antagonists can be a problem (ankle swelling) and chronic cough on the ACE inhibitors is well described.

In patients with ACE inhibitor intolerance (usually cough which resolves on stopping the drug) and not controlled on HCTZ and amlodipine, an angiotensin receptor blocker may be appropriate – e.g. losartan 50 mg daily.

Beta-blockers are appropriate for hypertensive therapy if being given primarily as angina prophylaxis or after a confirmed episode of an acute coronary syndrome. They should no longer be used as second line therapy in otherwise uncomplicated hypertension.

Subsequent choices might include hydralazine (start at 25 mg 12 hourly, increase to 50 mg 12 hourly, but dosing much above 75 mg 8 hourly is seldom effectual). In patients with refractory disease (generally also with renal impairment) the addition of minoxidil may be needed (start at 2.5 mg daily, then 5 mg daily, then 10 mg daily as needed. Doses above 20 mg daily seldom achieve much extra.)

‘Compelling indications’ are associated diseases whose presence might sway choice of antihypertensives – e.g. ACE inhibitor in diabetes, LVH, heart failure, and stroke, thiazides in stroke and isolated systolic hypertension, furosemide in heart failure and chronic kidney disease, and beta-blockers in coronary artery disease.

Beta-blockers in uncomplicated primary hypertension.

The role of beta-blockers in treating patients with otherwise uncomplicated hypertension requires review in the light of a meta-analysis⁵ suggesting an increased risk of stroke in patients on these agents relative to patients on other antihypertensives (RR 1.16, 95% CI 1.04-1.30) although there was no difference in overall mortality or risk of myocardial infarction.

The beneficial effect on stroke reduction relative to placebo was only about half that expected: for the mixed duration trials, the overall absolute risk reduction in stroke was 0.2% (RR 0.81, 95% CI -.71-0.93). Importantly, the relative risk of death or myocardial infarction in the same study was statistically no different to placebo. Although it has been argued that this lack of benefit is specific to atenolol (lowers peripheral but not aortic pressure) there are sufficient reservations about beta-blockers in general to have them relegated to third line in some hypertension guidelines.

Differential effects of thiazide diuretics in obese and non-obese patients

The ACCOMPLISH trial⁶ compared an ACEI/Ca antagonist (benazepril/amlodipine) combination to an ACEI/diuretic (benazepril/hydrochlorothiazide) in more than 11 000 hypertensive patients. With a composite endpoint significantly in favour of the amlodipine arm (ARR 2.2%, 95% CI 1.0 to 3.3%) this industry-driven trial has been used to suggest that amlodipine is more effective than a thiazide, and that thin patients on diuretics fare worse.

It is worth remembering that more than 55% of the composite endpoint was made up of coronary revascularisation procedures, and of the ‘hard’ CVS endpoints, only myocardial infarction showed a significant reduction in favour of amlodipine. An alternative interpretation is that in a trial of high risk patients (BMI >31) where more than one third of patients had undergone a revascularisation procedure already, 75% were dyslipidaemic, and less than half were on a betablocker, using agents with effects beyond just BP lowering makes sense.The story that HCTZ doesn’t work in thin patients is based on a post-hoc sub-analysis of this trial,⁷ and equally could be seen as showing that calcium antagonists are better at preventing heart attacks in patients at high risk (BP control in non-obese – not thin – patients was the same regardless of the agents used.)

Secondary causes

The reported relative frequency of the various causes of secondary hypertension is influenced by the referral patterns pertaining to the reporting institutions, which are usually tertiary academic hypertension clinics. Causes worth considering are:

• Takayashu’s disease with renal vessel involvement.
• Polyarteritis nodosa.
• Primary hyperaldosteronism.
• “Primary” renal artery stenosis, which is usually due to fibromuscular hyperplasia in younger patients.
• Hypercortisolism.
• Phaeochromocytoma.

Deciding which patients warrant extensive investigation is sometimes a little problematic and firm rules are difficult, but in general a younger patient with more difficult to control blood pressure would warrant more aggressive investigation than an older person with borderline control. In addition, any suggestive findings on examination or history should be taken further.

This means that you need to ask about symptoms of new weight gain, episodic sweating or headache, and malaise, and you need to examine for missing or discrepant pulses, an abdominal bruit and features of Cushing’s…

Investigations in suspected secondary hypertension:

• U&E (all patients)
• ESR or CRP (suspected PAN or Takayashu’s)
• Aldosterone-renin ratio
• 24 hour urinary cortisol
• 24 hour urinary VMA/NMA.

Investigating for primary aldosteronism

The test of choice is the aldosterone-renin ratio, which ideally should be measured off diuretics (including spironolactone) and ACE inhibitors. You will need one lithium and one EDTA tube. Some labs measure renin activity and others measure renin ‘mass’ by immunological methods. Using mass, an aldo/renin ratio of >64 pmol/mIU⁸ warrants further investigation. (Start by repeating it.) If the renin result is given in activity units (ng/ml/hr) then a ratio > 1000 pmmol/(ng/ml/hr) in the context of a plasma aldosterone of >500 warrants repeating.⁹ If similar, proceed to adrenal CT scan.

Perspective – aldosterone-renin ratio

Apart from the confusion about units and activity, this very popular screening test has been only poorly evaluated. One review¹⁰suggests that the test characteristics have yet to be established…

Conversion factors: aldosterone: ng/dl x 27.74 = pmol/L

renin: ng/ml/hr x 0.2778 = ng/L/sec;

renin: ng/ml/hr x 0.7943 = nmol/L/hr.

(Using ng/ml/hr and pmol/l, an A/R ratio <1000 with aldo < 1000 suggests essential hypertension, and an A/R ratio > 1000 with an aldo < 500 suggests low renin hypertension.)

Perspective – what are you trying to do by diagnosing Conn’s?

A recent review¹¹ makes the point that aldosterone-producing adenomas are benign tumours, and the aim of management is to normalise blood pressure. Hypokalaemia can usually be controlled with spironolactone. The group estimated that only about 6% of patients with hypertension referred to specialist centres have primary aldosteronism, and only 50% of patients with primary aldosteronism have adrenal adenomas, and in those, only half are cured by surgery. In other words, only 1.0% – 1.5% of patients referred will benefit from surgery.

Investigating for renal artery stenosis.

Renal artery stenosis is a potentially reversible cause of hypertension, due to a variety of causes (fibromuscular dysplasia, Takayasu’s or other vasulitides, neurofibromatosis, dissection or aneurysms, retroperitoneal fibrosis or other extrinsic compression from masses, and atherosclerosis). Suspect the diagnosis if:

• Hypertension is first diagnosed before 30 years. In the absence of evidence of end-organ disease, a new diagnosis of hypertension in older individuals, e.g. over 55, should also rouse suspicion.
• Accelerated or difficult to control hypertension in spite of good compliance.
• Abdominal bruit
• Rising creatinine (>15%) on starting ACE inhibitor.
• Sudden onset unexplained pulmonary oedema.

A plain abdominal ultrasound showing a more than 1.5 cm discrepancy between kidney sizes should further heighten suspicion, but lack of a discrepancy does not exclude the diagnosis. In good hands and with a relatively thin patient so that visualisation is easy, a Doppler is the ideal next investigation as it is non-invasive, does not involve contrast injection, and is relatively cheap, other than in terms of radiologist time. In practice a CT angiogram is faster and allows pictorial representation of the stenosis, so is the popular way to go.

If a stenosis is identified, it is still not entirely clear what the natural history of the lesion will be, but in general referral is appropriate. Transluminal angioplasty is successful at fixing the blood pressure in between 10 and 75%. Surgery is another option. If a procedure is not used, then calcium blockers are reasonable choices for assisting with blood pressure control.

Perspective – investigations in suspected renal artery stenosis.

The figures in the following table are calculated from values provided in a review:¹²

	Sens	Spec	LR+	LR-	Comment
Optimum performance (i.e. best reported results)
IVP	0.83	0.89	7.5	0.2	Contrast load, false positives up to 41%
Renin + captopril	0.57	0.66	1.7	0.7	Works best if normal renal function
DTPA scan	0.9	0.93	12.9	0.1	Doesn’t work for bilateral RAS or in uraemia
Doppler	0.98	0.98	49.0	0.0	Time consuming, operator dependent
CT angio	0.92	0.98	46.0	0.1	Moderately operator dependent, contrast load.
Worst performance (i.e. worst reported results)
IVP	0.83	0.89	7.5	0.2
Renin + captopril	0.57	0.66	1.7	0.7
DTPA scan	0.83	0.85	5.5	0.2
Doppler	0.75	0.87	5.8	0.3
CT angio	0.59	0.82	3.3	0.5

An adequate Doppler report (obtained in a patient after overnight fasting) should specify aortic velocity at the level of the renal arteries as well as renal to aortic velocity ratio (RAR). Important stenosis (>60%- 99%) is highly likely if the peak systolic velocity in a renal artery is more than 3.5 times that in the aorta. A renal artery end diastolic velocity of more than 1.5m/s suggests greater than 80% stenosis.

The table illustrates an important dilemma in the interpretation of the results of special investigations. No test is perfect, and most of those listed have a learning curve associated with their performance. Units that publish results against a gold standard (angiography) have of necessity performed both procedures in a large series of patients, and hence are relatively experienced. Unless units with lesser experience (the sort found in radiology departments in public service hospitals) were to publish their results, it becomes a value judgement how much worse they are performing (if at all – they might be just as good, or better!) than those who do publish. In short, suboptimal investigative performance is rarely quantifiable.

Perspective – what are you trying to do by diagnosing RAS?

In patients with high grade stenosis not controlled on adequate medical therapy, surgical or angioplastic correction of the stenosis is appropriate; however a study¹³ looking at atherosclerotic RAS in patients on two or more drugs found little difference in outcome between percutaneous angioplasty and medical therapy, although BP was a bit lower in the former (mean 26/10 mmHg).

Prognosis and urgency for blood pressure control

There are two broad groups of patients with hypertension – those with accelerated hypertension and evidence of new end organ damage, and those with chronically elevated blood pressure where it is desirable to reduce the level, but there is no urgency to do so. It is important to recognise the difference, because ‘blood pressure cosmetics’ in the situation of pseudo-emergencies ¹⁴ (an incidentally discovered high reading in an otherwise well and stable patient) can actually cause harm by dropping the blood pressure too quickly. Sublingual nifedipine is absorbed no more quickly, and possibly even less well than the conventional oral route.¹⁵ There is very little reason to use this route, other than in the rare instance of the patient where the enteral route is unavailable and intravenous medication is considered undesirable.

Economic factors in pragmatic BP control

Treating hypertension is usually accepted unquestioningly as one of medicine’s universal ‘goods’ with only benefit to the patient and, because the medication is often quite cheap, little cost to the health care funder. There are a number of problems with these assumptions:

The blood pressure control obtained in a primary care clinic is often worse than that in the carefully co-ordinated adequately funded randomised trials used to prove drug efficacy – take a look at some clinic notes if you don’t believe this.

The risk profile of many hypertensive patients is also worse than those in RCTs of drug efficacy.

The cost effectiveness of drugs given but not of benefit is infinite, no matter how cheap the actual medication.

Hence pragmatic trials, where medication is given in situations more closely resembling the real world, are better at determining true population efficacy.

The ALLHAT trial has demonstrated quite convincingly that simple diuretics are as effective as newer agents. Simply demonstrating that an agent has certain ‘superior’ biological features in terms of on-paper physiology is not the same as showing superiority in a large cohort of patients treated in real world situations.

Perspective – ALLHAT and all that

This trial¹⁶ compared a thiazide diuretic, amlodipine and lisinopril in 33 357 patients and found no difference between primary (fatal and non-fatal MI) and some secondary outcomes (death, CRF and peripheral vascular disease) between the three groups. Lisinopril seemed to fair worse in some of the other outcomes, but the study protocol did not allow atenolol to be combined with it although diuretic-atenolol (and amlodipine-atenolol) combinations were allowed.¹⁷

There is a clear evidence of the efficacy of blood pressure lowering drugs in reducing all cause mortality and cardiovascular endpoints such as stroke and myocardial infarction. The magnitude of benefit is related to pre-treatment risk factors such as age, the presence of end organ damage, and other modifiable risks such as smoking, hypercholesterolaemia, and diabetes, but the risk reduction relationship is linear down to a blood pressure of 115 systolic and 75 diastolic¹⁸: the relative risk of cardiovascular disease doubles with every 20/10 mmHg rise in BP.

In the absence of other risk factors such as cardiac failure and angina, low dose thiazide diuretics are as effective as beta-blockers, ACE inhibitors, calcium antagonists, and angiotensin receptor blockers when each agent is being used as monotherapy.¹⁹ In this network meta-analysis, thiazides use resulted in a statistically significant 13.2 mmHg (95% CI 10.1 to 16.3) reduction in systolic blood pressure compared to placebo, but all of the other agents were less effective than this, although not statistically significantly so.

When pooled across large numbers of studies with widely differing baseline risk, the ARR in mortality of antihypertensive use is probably of the order of 1% to 2% over 5 years (e.g. NNT ranging from 69 for elderly patients with isolated systolic hypertension ²⁰to 32 for African-American women.²¹ In the latter review, no benefit was found for treatment in low-risk young white women.)

Studies comparing the cost-effectiveness of BP control as a function of age and drug use yielded wide variation in cost ²² (Euros 47 325/QALY for a 30 year old woman prescribed an ACE inhibitor to Euros 645/QALY for an 80 yr old man given a thiazide.)

Perspective – ‘clinical inertia’ in medical management

Particularly in clinical situations characterised by shortages of medications and shortages of time per patient there is a considerable tendency to overlook the treatable, particularly when it is asymptomatic. A review²³ has identified three core problems:

• An overestimation by clinicians of the amount of clinical benefit treatment provides.
• Using soft reasons to avoid tightening up on therapeutic targets.
• Not knowing the absolute benefits of managing life style diseases.

However, enthusiasm for targeting all risk factors should always be tempered by a desire to model therapy for the individual patient’s needs and circumstances – for instance very tight glucose control in a partially sighted elderly woman living on her own in a rural community may not always be beneficial.

Perspective – BP targets and how low should one go…

It has been suggested that traditional BP targets (140 – 160 /90 – 100) may not be low enough. A systematic review²⁴ looking at this issue found no evidence that further reduction in diastolic blood pressure below the 90 – 100 mmHg value resulted in mortality or morbidity advantages, and this is reflected in the 2014 JNC8 guidelines…

And then along came SPRINT,²⁵ which linked a mortality advantage to targeting a systolic BP of 120 mmHg rather than 140. There was a statistically significant 0.37% per year reduction in all cause mortality in a trial of 9361 patients. The trial was stopped early, and patients were a little unusual: two thirds men, mean age 68, with more than a quarter over 75, 28% had CKD, and the average BMI was 30. Patients were excluded if they were diabetic, or had a previous stroke or heart failure. Specifically, patients ended up taking three rather than two agents, and the group taking more agents were more likely to be taking one or more of beta-blocker, thiazide, and calcium antagonist. The improved outcome may have been linked to the BP target, but equally coud be explained by using more cardio-protective agents. Currently, the jury is still out on the ideal BP target.

Management of hypertensive urgencies and emergencies.

It is crucial to recognize not only what is a hypertensive crisis but also what is not an emergency.

²⁶

Hypertension severe enough to be causing acute damage is rare. The chronically non-compliant person who appears yet again with a systolic of 200 and a diastolic of 120, who is feeling completely well, has Grade II or less fundal changes and isn’t in heart failure or renal failure can be labelled as having asymptomatic severe hypertension. Start two drugs (e.g. furosemide and an ACE inhibitor) and follow closely. Once symptoms develop, the label becomes hypertensive urgency, and ideally such patients should all be admitted for BP control within 48 hours.

True hypertensive emergencies, where BP should be reduced more rapidly, include:

Young individuals with acute glomerulonephritis or eclampsia (GPH).

High blood pressure associated with neuroendocrine tumours, specifically phaeochromocytomas.

Clear symptomatic evidence of sudden worsening of blood pressure, usually identified by one or more life-threatening complications:

• Severe headache or even encephalopathy/confusion
• LV decompensation
• Acute renal failure
• Aortic dissection. (The only situation where bringing BP down within minutes rather than hours is considered worthwhile.)

Therapy of hypertensive emergencies:

Oral. Promptly started oral therapy is superior to beautifully titratable IV medication whose administration is delayed by imperfect logistics.

Give a diuretic such as furosemide 80 mg/d. Certain patients with accelerated hypertension may be significantly pre-renal – in the absence of an available U&E, check for a marked postural change in blood pressure.

Start captopril 6.25 mg PO simultaneously, and increase the dose to 12.5 mg if no response at 30 minutes. Thereafter increase to 25 mg 3x/d. Pro-drugs such as enalapril and perindopril are not ideal, but use them if they are all that is available. Captopril will start to act within about 30 mins, enalapril within 2 to 4 hours.

An alternative that is not very well studied is amlodipine 5 mg. Because abrupt BP changes can be harmful, the immediate release formulation of nifedipine is no longer considered appropriate, either orally or sublingually.

Another option is oral hydralazine 25 mg 8 hourly, increasing to 50 mg 8 hourly.

Whatever agent is used (including the IV ones) ensure that stable maintenance therapy is given so that the BP doesn’t rise again hours or days later.

Intravenous. This is ideal but not always practical. If facilities for careful monitoring are available (ICU or high care ward) then consider:

Labetalol as an infusion at 2 mg/min to a maximum of about 100 mg, or as 20 mg boluses every 10 minutes. It works in 10 minutes and the effect lasts 3-4 hours.²⁷. If starting an infusion (2mg/ml) begin at 30 mg/hr, and increase every 30 mins until control achieved, then continue at 5 to 20 mg/hr, with caution about exceeding a cumulative dose of 300 mg, although information to support this last caveat is weak²⁸.

Glyceryl trinitrate 5-10 mcg/min IV is appropriate in patients with angina or pulmonary oedema (see separate entry for administration details.) It is mainly a venodilator and isn’t a good agent for aortic dissection.

Nitroprusside IV works well, but in renal failure should be used very cautiously if at all. For dissection it should be combined with a beta-blocker.

Intravenous verapamil is often available in smaller hospitals, and in the absence of frank cardiac failure, may be considered²⁹ – give a bolus of 0.15 mg/kg (i.e. about 5-10 mg) slowly IV, and then follow with an infusion at a rate of 0.005 mg/kg/min (put 20 mg in 500 ml of 5% DW and infuse over about one hour.) It is contraindicated in heart failure or heart block, and safety is unproven.

Magnesium sulphate is first choice in gestational proteinuric hypertension³⁰ but other options are IV labetalol, oral hydralazine or oral nifedipine.) Avoid ACE inhibitors in pregnancy.

Sympathetic crises (phaeochromocytoma, and methamphetamine or cocaine ingestion) can be exacerbated by beta-blockers, including labetalol, because of the resultant inadequately opposed alpha-adrenergic vasoconstriction. Verapamil or nitroprusside are possibilities. Doxazosin is appropriate if available.

Perspective – the risk of a sudden vascular event in accelerated hypertension.

Treating accelerated hypertension is a self-evident ‘good’. A 2008 systematic review ³¹was unable to show that medication improved morbidity or mortality in patients with hypertensive emergencies, simply because there were no adequate quality studies. Intuitively, the more abrupt the hypertensive crisis, the more likely are (modifiable!) short term adverse outcomes. Thus it is considered desirable to lower the pressure promptly. What is unclear but of clinical relevance is exactly how much benefit is derived from ultra-rapid (e.g. drug infusions in ICU) BP lowering compared with achieving the same effect over 24 hours with the use of oral agents. A

Studies from the era before adequate antihypertensives were available suggest that mortality at one year was about 90% and at 6 months was 50%. Referral patterns may influence the modern survival rates reported in the literature, but a study from a hospital in Birmingham³² showed median survival of 39.2 months before 1970, 68.6 months in the 1970s, and >144 months in the 1980s. (i.e. 3, 5 and 12 year median survival respectively). Five year survival with ‘modern’ therapy was still only 74%. (Causes of death: renal failure 40%, stroke 25%, myocardial infarction 10%, cardiac failure 10%.) A similar sort of case series done at about the same time in Nigeria showed one year survival of 37.5% ³³ (with some loss to follow-up).

It is important to treat accelerated hypertension promptly but the incremental benefit from intravenous therapy is poorly documented.

Management of chronic hypertension – therapeutic options

The concept of stepped care – using one agent and escalating the dose till either side-effects occurred or dose ceiling was reached – has been superseded by a more friendly, and arguably more logical, strategy of adding more agents in lower doses rather than further pills of the same type. The ALLHAT trial provided good evidence that starting all patients without contra-indications on a thiazide diuretic is appropriate. In patients with other indications for a beta-blocker, this is a reasonable alternative. Next agents would be either an ACE inhibitor or a slow-release calcium antagonist.

Management of hypertension – night time dosing

There was a fashion for this based on a trial³⁴ with results that were probably too good to be true.³⁵

The subsequent TIME trial³⁶ showed that timing made absolutely no difference to CVS outcomes and provided a reminder that taking headline findings from trials and translating that into practice without careful perusal of trial quality can be problematic.

Management of chronic hypertension – concordance

One pill once a day is better than polypharmacy. If you find yourself writing up the third or fourth antihypertensive on the same script, sit back and take a breath – you are probably missing something. Once you start writing up pills that need to be taken more than once daily, you should be thinking very hard. Patients don’t take pills they don’t like, so it is worth exploring key reasons for dislike of antihypertensives:

Myalgia and malaise – beta-blockers

Cramps –patients who complain of calf cramps on diuretics are often intermittently adherent, so ask. Taking medication regularly usually solves this.

Cough – the ACE inhibitor package insert correctly mentions this, and it is well known amongst patients who proceed to stop the drug when they have a cold, or even worse, when LVF gets worse.

Impotence. This is a common reason for stopping once the association is worked out. Beta-blockers are often the cause, but quite a range of other agents have been associated with this.

Ask the patient which pills are least favourites – you will usually be told, and this often allows access to the issues surrounding that dislike. Have you ever asked a patient what sort of blood pressure regimen he or she would like?

Difficult to control hypertension – consider:

• poor concordance (the regimen may make the patient feel sick, or be too complicated to follow) Ask to see the packets, and ask about timing of doses, etc.
• inadequate salt loss (subtherapeutic diuretic doses in renal impairment)
• white coat hypertension (you or the environment make the patient anxious)
• concurrent use of medication which reverses the blood pressure effects you are trying to achieve (usually non-steroidal analgesics)
• an inefficacious regimen (e.g. ACE inhibitor without diuretic, once daily dose of a short acting drug, or subtherapeutic dose)

The incremental improvement from increasing doses is small for many antihypertensives, and the cost and side effects escalate rapidly. If your regimen isn’t working, review the causes rather than just increasing doses.

Blood pressure control – the rising creatinine.

As the blood pressure drops, the serum creatinine may rise. This reflects dysfunction of the normal autoregulation of glomerular perfusion pressure seen in hypertension, and in fact is probably an indication that therapy is likely to be beneficial. If the rise in serum creatinine is less than 25% of the initial value³⁷ (e.g. 160 micromol/litre going to 200) and once it has risen it remains static (repeat it after a week or so) then it is appropriate to continue with the blood pressure lowering agent.

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