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Question from practice

Behind recent hypertension headlines

My doctor measured my blood pressure again and says it’s still too high: 148 over 88, he said. He gave me this prescription [ramipril] but I don’t know if I want to get it. I’m nearly 70 and I’ve never had to take anything until now. I remember reading in the papers before Christmas about some new guidance in America that said some people are being given these blood pressure medicines when they don’t need them. And then just last week it was in The Telegraph that these medicines do more harm than good because they can make you fall down. What do you think?

 Patient (Diego Vito Cervo/Dreamstime.com)

Hypertension is often perceived by patients as a relatively benign condition until they experience a major cardiovascular event or present with significant end organ damage. The estimated annual number of deaths attributable to stroke or heart attack due to uncontrolled hypertension in the UK is 62,000[1].

Absolute risks are related to increasing blood pressure: it has been suggested that for every rise of 20mmHg systolic or 10mmHg diastolic between 115/75 and 185/115 the risk of heart disease and stroke doubles[2]. Moreover, data from 2011 show that almost two fifths of men and women receiving treatment for hypertension were unsuccessful in reducing their blood pressure to a level below 140/90mmHg[3].

Hypertension infographic (Jessica Fox/Dreamstime.com)

US guidance

Because hypertension has such a high impact on morbidity and mortality, its treatment has been identified as a priority both nationally and internationally, and a number of guidelines on prevention, detection, evaluation and treatment exist. The guideline of the Eighth Joint National Committee (JNC 8), released in December 2013 and published in JAMA in February[4], was much anticipated, a decade having passed since the previous (JNC 7) guideline, but it has sparked debate — and, indeed, some criticism — in cardiovascular circles.

The JNC 8 panel was originally selected by the US National Heart, Lung and Blood Institute in 2008 but after the institute announced its decision to stop developing clinical guidelines in 2013, the panel chose to continue independently. It developed evidence statements and recommendations based on a systematic review of literature and the updated guideline makes nine recommendations (see Panel 1: JNC 8 recommendations).

Panel 1: JNC 8 recommendations

Recommendation 1 In the general population aged 60 years or older, initiate pharmacological treatment to lower blood pressure (BP) at systolic blood pressure (SBP) of 150mmHg or higher or diastolic blood pressure (DBP) of 90mmHg or higher and treat to a goal SBP lower than 150mmHg and goal DBP lower than 90mmHg. (Strong recommendation — Grade A)

Recommendation 2 In the general population younger than 60 years, initiate pharmacological treatment to lower BP at DBP of 90mm Hg or higher and treat to a goal DBP of lower than 90mmHg. (For ages 30 through 59 years, Strong recommendation — Grade A; For ages 18 through 29 years, Expert opinion — Grade E)

Recommendation 3 In the general population younger than 60 years, initiate pharmacological treatment to lower BP at SBP of 140mm Hg or higher and treat to a goal SBP of lower than 140mmHg. (Expert opinion — Grade E)

Recommendation 4 In the population aged 18 years or older with chronic kidney disease (CKD), initiate pharmacological treatment to lower BP at SBP of 140mmHg or higher or DBP of 90mmHg or higher and treat to goal SBP of lower than 140mm Hg and goal DBP lower than 90mmHg. (Expert opinion — Grade E)

Recommendation 5 In the population aged 18 years or older with diabetes, initiate pharmacological treatment to lower BP at SBP of 140mmHg or higher or DBP of 90 mm Hg or higher and treat to a goal SBP of lower than 140mmHg and goal DBP lower than 90mmHg. (Expert opinion — Grade E).

Recommendation 6 In the general non-black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Moderate recommendation — Grade B)

Recommendation 7 In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. (For general black population: Moderate recommendation — Grade B; For black patients with diabetes: Weak recommendation — Grade C)

Recommendation 8 In the population aged 18 years or older with CKD and hypertension, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. (Moderate recommendation — Grade B)

Recommendation 9 The main objective of hypertension treatment is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, increase the dose of the initial drug or add a second drug from one of the classes in recommendation. The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with two drugs, add and titrate a third drug from the list provided. Do not use an ACEI and an ARB together in the same patient. If goal BP cannot be reached using the drugs in Recommendation 6 because of a contraindication or the need to use more than three drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed. (Expert opinion — Grade E).

Treatment targets

Perhaps the most notable change from the JNC 7 guideline is the relaxing of treatment targets in patients aged 60 and over to 150/90mmHg (from 140/90), and in those with renal disease or diabetes (both to 140/90mmHg). There is some concern that, as a result, blood pressure levels in patients will increase. And in comparison, European Society of Hypertension/European Society of Cardiology and National Institute for Health and Care Excellence guidelines (2013 and 2011, respectively) have more stringent targets of 140/90mmHg for patients up 80 years, and a target of 150/90mmHg suggested for those over 80[5],[6].

The difference is largely down to interpretation of evidence and inclusion and exclusion of trials. There are few randomised controlled trials assessing ideal blood pressure targets and even fewer involving specific patient subgroups such as those with diabetes. While some guideline development groups have recommended targets for specific subgroups this is often based on group consensus rather than RCT data. The JNC 8 has adopted a wide population based approach and chosen not to individualise treatment strategies in order that the guideline is user-friendly.

Evidence from five trials[7],[8],[9],[10],[11] showed that treating patients between the ages of 30 and 69 years to a target diastolic blood pressure less than 90mmHg resulted in a reduction in cerebrovascular events, heart failure and overall mortality. More recently there has been renewed interest in titrating diastolic blood pressure readings based on these earlier trials. The diastolic target is evidence based but the target systolic blood pressure in those under 60 years was added by the panel to ease guideline implementation because it believed that a single diastolic blood pressure reading may cause confusion. The systolic target in Recommendation 3 is one of expert opinion. (ie, there is insufficient evidence or the evidence was unclear or conflicting).

NICE, in its clinical guideline,5 interpreted the evidence differently, agreed different treatment targets and set a different age bracket. Other bodies, such as the ESC, have made a number of treatment targets for particular patient groups, and although this may better suit individual patients, it leads to a more complicated clinical guideline. Part of the criticism of the JNC 8 targets is that in only looking at RCTs to address targets there were few data from which to make definitive recommendations. There is a need for larger RCTs to compare different blood pressure targets in diverse patient populations.

A key message from the authors was the requirement to make the guidance simple. Treatment of an individual may be more or less aggressive depending on patient factors such as tolerability and quality of life.

It can be noted that the simplistic approach of JNC 8 guidance is in conflict with another recently published guideline from the American Society of Hypertension and the International Society of Hypertension. Only time will tell which guidance US prescribers will favour both in terms of treatment and targets. The current NICE guidance for hypertension should be followed in the UK. It will be interesting to see if the relaxation of targets adopted by the JNC 8 lead to improved outcomes and potentially fewer adverse effects from patients taking high dose antihypertensives. It is likely that blood pressure targets will be scrutinised in the next review of NICE guidance.

Prescribing options

JNC 8 also amended its drug therapy recommendations. There is marked variation in the initial choice of agent depending on which hypertension guideline the prescriber follows. Some guidelines place more emphasis on certain classes of antihypertensive as a first-line choice depending on co-morbidities and patient characteristics. A British Hypertension Society strategic review (2010–16) is suggesting that when treating a population, the mean effect of the four common antihypertensive agents (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers [ARBs], calcium channel blockers and diuretics ) on a QALY measure are similar whereas beta-blockers are marginally less effective[12]. Costs for these agents have dramatically fallen over the years, increasing cost effectiveness.

JNC 8 reviewed the four standard antihypertensives above and concluded similarly. In one study that the panel reviewed, the use of beta-blockers resulted in a higher rate of the primary composite outcome of cardiovascular death, myocardial infarction, or stroke compared with use of an ARB, a finding that was driven largely by an increase in stroke and, for this reason, they are not recommended first-line. This is in line with beta-blockers being removed from the “ABCD” (ACE inhibitor, beta-blocker, calcium channel blocker and diuretic) NICE algorithm (which is now “AC” only since a diuretic is also no longer routinely recommended).

In opting for simplicity and deciding to leave the choice of antihypertensive with the clinician and patient, the JNC 8 panel emphasised that the evidence supports BP control, rather than a specific agent used to achieve that control. It did note that in patients taking a thiazide-like diuretic, there was an improvement in heart failure outcomes but this improvement was not compelling enough to support its use as the single first-line choice. This recommendation is contrary to NICE and European guidance, which tend to be more specific about what agent(s) to choose first. (Panel 2 summarises the comparisons.)

 Panel 2: JNC 8 comparison with NICE and ESH/ESC

 GuidelinePopulation
Target BP (mmHg)
Initial prescribing options
JNC 8 2014
   
General<60yr<150/90Non black: thiazide type diuretic, ACEI, ARB or CCB; Black: thiazide type diuretic or CCB
General<60yr<140/90
Diabetes<140/90 Thiazide type diuretic, ACEI, ARB or CCB
ACEI or ARB
Chronic kidney disease (CKD)<140/90 
ESH/ESC 2013
     
General non-elderly<140/90 BB, diuretic, CCB, ACEI or ARB
General elderly <80yr<150/90 ACEI or ARB
General >80yr<150/90 ACEI or ARB
Diabetes<140/85  
CKD no proteinuria<140/90  
CKD with proteinuria<130/90  
 NICE 2011
General <80yr<140/90 <55years old: ACEI or ARB
General >80yr<150/90 >55years old or black: CCB
ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; CCB: calcium  channel blocker; BB: beta-blocker

Similar to other guidance, the first choice agent in black patients is based on interpretation of the pre-specified subgroup analysis of the ALLHAT trial. The JNC 8 panel believed that thiazide-like diuretics and calcium channel blockers were shown to be more effective in improving cardiovascular outcomes when compared with ACEIs in the black patient subgroup and so these are the first-line option.

There are no randomised controlled trials and little clinical evidence on how to treat patients who have not achieved target blood pressure readings with one agent. The choice between dose escalation and adding further agents tends to be based on clinical judgement and patient tolerability, which has led to the guidance offering flexibility with choice. ESC guidance suggests that the question of what the first-line agent should be, should actually be what combination should be used first based on the premise that monotherapy is only effective in a small majority of patients and most require the combination of at least two agents to achieve targets.

Since so many patients do not reach blood pressure targets on one agent it may be that future guidelines (and research) look to recommend which combination of antihypertensive should be given initially rather than trialling one agent knowing that most will require a second agent.

Antihypertensives and falls

Pharmacists will know that antihypertensive drugs have long been implicated as a cause of falls in the elderly, due to orthostatic hypotension. The falls are related to the target used for blood pressure as opposed to choice of agent. (There is much debate as to whether choice of agents contributes greater to the risk.) A three-year observational study published in JAMA and reported in the national papers last week has added to the evidence. In particular, it was noted that the proportion of patients taking antihypertensives and who died as a result of falls was similar to that found in other studies for patients expected to die from a heart attack or stroke when they had not been treated with antihypertensives (PJ 2014;292:221).

Multiple factors are involved in falls but often polypharmacy, especially in the elderly, is one. Antihypertensives taken together with anxiolytics, sedatives and opioid-based analgesics will all contribute to an increased risk of falls. Warning signs, such as dizziness when standing up or unsteadiness, should prompt a referral to the GP for blood pressure and medication review.

A trial reviewing timing of medication (to see whether taking tablets at night will reduce the likelihood of postural hypotension) is currently under way.

This patient

Adherence is crucial if therapy is to be successful and so this patient’s concerns need to be addressed. The key message for patients is that lowering high blood pressure will result in reduced risk of cardiovascular disease. It is good practice to assess the cardiovascular risk of someone presenting a prescription for an antihypertensive for the first time.

The UK based QRISK2 calculator available online is a good way to undertake a cardiovascular disease risk assessment. The results of the report are displayed in a patient-friendly manner and based on an individual’s risk for cardiovascular disease which could prompt additional therapy such as statins to reduce their cardiovascular disease risk.

Current NICE guidance suggests a more demanding target of 140/90 for this patient although if she has side effects or experiences effects suggestive of low blood pressure then she should contact her GP. Home blood pressure monitoring whereby patients take control of their own condition as opposed to waiting for their next clinic appointment will allow a far better assessment of any prescribing decisions has on the individual’s blood pressure, and could be recommended here.

The adoption of more relaxed JNC 8 targets may lead to less aggressive dosing and potentially fewer side effects and an improvement in patient compliance although, in practice, it may also lead to a general increase in blood pressure because targets are often not met.

In terms of her concern about falls, this patient may be reassured to some extent: she is not taking any other medicines and does not appear frail. The JAMA study noted that the risk of falls with antihypertensives was greater in those who had had a previous fall so the patient could be asked about any previous falls. She could also be advised to get up slowly and look out for and report any dizziness or unsteadiness. It may also be worth asking her whether she lives alone.

Our patient is black and has been prescribed ramipril but, based on the NICE guidance she should be prescribed a calcium channel blocker. Most guidelines consider hypertension with no co-morbidities. If this patient had diabetes, then an ACE inhibitor would, indeed, be suitable for first-line use. In general, if medicines other than calcium channel blockers are prescribed for black patients it is worth checking co-morbidities, previous adverse drug interaction and the patient’s preference with respect to adverse events. Since most patients will require two agents the initial choice, although ideally based on NICE guidance, may differ if the patient expresses concerns about side effect profiles or has tried other medicines previously.

Finally, although we have focused on the pharmacological measures, we must not forget non-pharmacological considerations. In line with most hypertension guidelines JNC 8 acknowledges that lifestyle factors have a large impact on both hypertension and associated risk factors with recommendations to encourage weight loss, reduction in sodium intake to less than 2.4 grams (ie, 6g of salt) per day, and at least 30 minutes of aerobic activity most days of the week.

In addition, to delay development of hypertension, improve the blood pressure lowering effect of existing medication, and decrease cardiovascular risk, alcohol intake should be limited. All these factors should also be discussed with the patient in this case.

Key points

  • The key message for patients is that lowering blood pressure will result in reduced risk of cardiovascular disease.
  • Performing a QRISK calculation and encouraging home monitoring of blood pressure may help support understanding and adherence.
  • Pharmacists should be prepared to advise on health stories in the media.

 

About the authors

Sotiris Antoniou is consultant pharmacist, cardiovascular medicine at Barts Health NHS Trust, and Paul Wright is lead cardiac pharmacist at The Heart Hospital, University College London Hospitals.

Ask the expert is open until 24 March 2014. 

 

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11135402

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