Walking
4/2mmHg reduction with 150 minutes of moderate intensity walking a week.
more
Aerobic exercise
5/3mmHg reduction with 30-60 minutes aerobic exercise 3 x a week.
more
Weight loss
4/3mmHg reduction with weight loss of about 4 kilos.
more
Alcohol intake reduction
3/2mmHg reduction with lowering alcohol intake by two-thirds (from a baseline of 3-6 units per day).
more
Salt intake reduction
5/3mmHg reduction with lowering salt intake by 4.4g/day
more
Much of this evidence is described as LOW quality. Why?
more
Many of the RCTs included in the reviews in this section are small and quite old (pre-2000), when the conduct and reporting standards for research were less rigorous, so there is a risk of bias in many of these results.
This means that the estimates of benefit are uncertain.
However, there is much observational evidence showing associations between healthy lifestyle factors and lower blood pressure which supports the findings from the RCTs.
References
more
1)Lee LL, Mulvaney CA, Wong YK et al. Walking for hypertension. Cochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD008823. DOI: 10.1002/14651858.CD008823.pub2
2)Halbert J, Silagy C, Finucane P et al. The effectiveness of exercise training in lowering blood pressure: a meta-analysis of randomised controlled trials of 4 weeks or longer. J Hum Hypertens 1997; 11, 641–649
3)Semlitsch T, Krenn C, Jeitler K et al. Long‐term effects of weight‐reducing diets in people with hypertension. Cochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD008274
4)Xin X, He J, Frontini MG et al. Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension 2001; 38(5): 1112-1117
5)He FJ, Li J, MacGregor GA. Effect of longer‐term modest salt reduction on blood pressure. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD004937. DOI: 10.1002/14651858.CD004937.pub2
Stage 1 hypertension means: clinic BP 140-159/90-99mmHg.
NICE recommends considering drug treatment for adults with Stage 1 hypertension and a baseline QRISK score of 10% or more.
The amount of cardiovascular risk reduction for an individual depends on their baseline risk.
Here, “combined cardiovascular events” means: fatal and non-fatal angina, MI, TIA and stroke.
|
We have presented information on Stage 1 hypertension separately, as the evidence base is more uncertain than that for Stage 2+3. Here, we show a lower risk reduction (RRR 12%) from drug treatment for Stage 1 hypertension, in line with the most recent NICE review. However, newer research suggests that the benefits may in fact be similar to those for treating Stage 2+3 (a RRR of 28%). This is uncertain, see the ‘Uncertainties and controversies’ button below. |
Figures derived from the 2019 NICE Guideline1:
Data detail
NICE acknowledged a challenge with the evidence base for stage 1 hypertension in that no ideal direct evidence exists for the treatment of stage 1 hypertension in patients without co-morbidities.
For their cost-effectiveness analysis, they applied the results of this systematic review which showed a 12% relative risk reduction (RRR) for combined cardiovascular events in a population with many patients with diabetes and CKD. This RRR has been applied here to baseline QRISK scores to give a rough estimate of benefits of treatment.
References
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019 . (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
2)Brunström M, Carlberg B. Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis. JAMA Intern Med 2018; 178(1): 28-36
| This research provides some indication of the treatment effect.
There is a high possibility that the true effect is smaller or greater. |
NICE rated this evidence as LOW – VERY LOW quality1.
Although the data was derived from:
there is uncertainty about the results because of:
Reference
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019 . (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
The population characteristics in this systematic review1 were:
Reference
1)Brunström M, Carlberg B. Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis. JAMA Intern Med 2018; 178(1): 28-36
The benefits of treating stage 1 hypertension in people with no established cardiovascular disease or co-morbidities such as diabetes and CKD are uncertain due to a lack of direct evidence.
NICE made a pragmatic recommendation in their guideline. However, you may hear different opinions – this is a brief summary of key aspects of the debate:
2012 Cochrane review: not enough evidence of treatment benefit
More
This review1 could find only 4 trials in patients with stage 1 hypertension and no co-morbidities.
These did not show a benefit, but neither did they prove a lack of benefit.
This is because the trials were not large enough to provide high enough rates of cardiovascular events. Most used mostly old-fashioned drugs, so we do not know the effect of newer drugs in this population.
2015-2016 systematic reviews including patients with CVD and other co-morbidities: evidence of benefit?
More
A number of large systematic reviews were published in the wake of the Cochrane review. These reported consistent relative risk reductions in CV events with blood pressure treatment across all levels of baseline blood pressure. For example:
However, these reviews looked at trials involving patients with all stages of hypertension and/or established CVD and/or co-morbidities such as CKD, diabetes and heart failure.
The data was then combined to infer a treatment benefit for stage 1 hypertension without co-morbidities.
However, these results are “indirect” and may be affected by benefits of treatment for the co-morbidities themselves (like beta-blockers for CHD or ACE inhibitors for heart failure or CKD).
There is argument about whether extrapolating data across such diverse groups of patients is statistically or clinically sound.
There is a body of opinion that does feel this is robust evidence.
2019 NICE’s approach: use data from primary prevention populations including those with type 2 diabetes
More
NICE decided not to include the systematic reviews containing large numbers of patients with co-morbidities, taking the view that these would not deliver applicable enough evidence4.
They selected evidence based mainly on patients without established cardiovascular disease, but accepted the inclusion of co-morbidities such as type 2 diabetes and CKD (which could be viewed as cardiovascular risk factors)5.
The inclusion of these patients means that statistically significant effects of treatment can be demonstrated (unlike the 2012 Cochrane review).
This research suggested a Relative Risk Reduction in cardiovascular events of 12% for drug treatment of stage 1 hypertension
A practical approach?
When considering hypertension treatment for a patient without diabetes or CKD based on this evidence, we assume that they would get the same relative benefit as those with these co-morbidities.
We can adjust our estimates of benefit for an individual by using a baseline QRISK score, which will take into account whether or not they have diabetes or CKD.
Evidence update since NICE guidleine
more
In 2021, a series of individual participant data meta-analyses were published by the Blood Pressure Treatment Triallists Collaboration (BPTTC)6,7.
These pool data from large numbers of trials and allow new insight into the benefits of blood pressure treatment across different baseline BP thresholds.
The authors suggest that this evidence shows an equal benefit of drug treatment across hypertension stages, so it may be that the relative risk reductions for stage 1 hypertension are the same as those shown in the Stage 2+3 hypertension section here.
NICE have yet to review these studies.
References
more
1)Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD006742. DOI: 10.1002/14651858.CD006742.pub2
2)Ettehad D, Emdin CA, Kiran A et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387(10022); 957-967
3)Zanchetti A, Thomopoulos C, Parati G. Randomized Controlled Trials of Blood Pressure Lowering in Hypertension: A Critical Reappraisal. Circ Res 2015; 116(6): 1058-1073
4)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019 . (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
5)Brunström M, Carlberg B. Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis. JAMA Intern Med 2018; 178(1): 28-36
6)Blood Pressure Lowering Treatment Trialists’ Collaboration. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021 May 1;397(10285):1625-1636.
7)Blood Pressure Lowering Treatment Trialists’ Collaboration. Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis. Lancet. 2021 Sep 18;398(10305):1053-1064
3 drug classes have the strongest evidence regarding cardiovascular outcomes:
First-line treatment
NICE recommends which of these to choose as first line for particular groups of people1:
more
However, the difference in outcomes between these three classes is not great. Some details here:
more
A 2018 Cochrane review2 provides figures for the relative risk reduction of different outcomes using different drug classes as first-line treatment.
CCBs show the best relative risk reduction for stroke, although the evidence is less certain than for low-dose thiazides:
| Low-dose thiazide | CCB | ACEi | |
| Stroke | 32% (23-40%) | 44% (18-59%) | 35% (18-48%) |
| CHD events | 28% (16-39%) | 23% (n/s) | 19% (6-30%) |
| Total mortality | 11% (3-18%) | 15% (n/s) | 17% (5-28%) |
| Evidence quality | High | Low* | Moderate/low** |
Relative risk reductions (with 95% confidence intervals) on outcomes by drug class
n/s, not statistically significant
* Rated low quality as only one trial and wide confidence intervals. ** Rated moderate/low quality as wide confidence intervals and some risk of bias
Second- and third-line treatments
The three drug classes can be combined in any order.
Other drug classes: see the “Resistant hypertension” button.
References
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019 . (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
2)Wright JM, Musini VM, Gill R. First‐line drugs for hypertension. Cochrane Database of Systematic Reviews 2018, Issue 4. Art. No.: CD001841
3)Helmer A, Slater N, Smithgall S. A Review of ACE Inhibitors and ARBs in Black Patients With Hypertension. Ann Pharmacother 2018; 52(11): 1143-1151
A target of below 140/90mmHg (clinic reading) is recommended for most people.
For those aged 80 and over, NICE recommends 150/90mmHg, and to use clinical judgement for those with frailty and multimorbidity1.
Evidence reviews by NICE in 2019 and Cochrane in 2020 found no benefit from treatment to lower targets1,2.
more
NICE reviewed 3 RCTs including 12,559 patients:
No convincing evidence of benefit was found from more intensive treatment
Cochrane reviewed 11 RCTs including 38,688 patients:
No convincing evidence of benefit was found from more intensive treatment
What about the SPRINT study? Didn’t that show benefit from low BP targets?
more
This US study, published in 2015, generated a lot of publicity and is cited by many as evidence to support lower BP targets.
It was included in both the NICE and Cochrane reviews described above, though was judged to have important limitations.
What did the study do?
What were the headline results?
| Benefits | Absolute Risk Reduction | Number Needed to Treat | Relative Risk Reduction |
| Total mortality | 1.2% | 85 | 26% |
| Heart failure | 0.8% | 123 | 38% |
| Harms | Absolute Risk Increase | Number Needed to Harm | Relative Risk Increase |
| Acute kidney injury/acute renal failure | 1.8% | 56 | 70% |
| Serious electrolyte abnormality | 1% | 100 | 37% |
| Serious hypotension | 1.4% | 72 | 70% |
| Serious syncope | 1.1% | 93 | 44% |
So, at face value, the trial seems to show a small but important benefit in overall mortality, but at the cost of hospital visits with serious side effects (there’s no data on primary care visits or side effects experienced at home).
What are the criticisms of this trial?
Though the trial was large and of high quality, there were some particular features which may affect its applicability:
Conclusion?
This study may provide evidence that the lower blood pressure target has benefit, but this is uncertain and comes at a significant risk of harm.
For patients who are keen to reduce their cardiovascular risk as much as possible, are at low risk of side effects and who can be adequately monitored, a lower target might be appropriate.
References
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019. (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
2)Arguedas JA, Leiva V, Wright JM. Blood pressure targets in adults with hypertension. Cochrane Database of Systematic Reviews 2020, Issue 12. Art. No.: CD004349
3)The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015; 373: 2103-2116
Of the combined cardiovascular events, how many are MIs, how many are strokes and how many are deaths?
This varies depending on age and sex, the numbers below are intended to be a rough guide only:
These two examples use very approximate numbers to give you an idea:
Data detail
For their Lipid guideline in 2019, NICE conducted a health economic analysis which used figures for proportions of first CV events in people of varying ages. These numbers were used to estimate the proportion of CV events in someone at a 40% baseline risk. Then the relative risk reduction of blood pressure treatment1 on each event was calculated. A similar method was used to develop the NICE statin decision aid2.
References
1)Brunström M, Carlberg B. Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis. JAMA Intern Med 2018; 178(1): 28-36
2)Patient decision aid: user guide for healthcare professionals. Implementing the NICE guideline on lipid modification(CG181). [Internet]. [London]: NICE; 2014 Accessed Mar 2021
Resistant hypertension means: hypertension which is uncontrolled despite treatment with 3 classes of drugs (ACEi or ARB+CCB+thiazide).
NICE suggests 3 additional drug classes to consider in addition1:
These have no or very limited evidence of benefit on cardiovascular outcomes, but do lower blood pressure.
BP lowering effect of these drugs in patients with resistant hypertension already on standard treatment:
| Spironolactone 25-50mg | Bisoprolol 5-10mg | Doxazosin 4-8mg | |
| Mean difference in SBP compared to placebo over 12 weeks | -8.7 mmHg | -4.2 mmHg | -4.6 mmHg |
Side effect rates of these drugs seen in this trial:
| Placebo | Spironolactone 25-50mg | Bisoprolol 5-10mg | Doxazosin 4-8mg | |
| Dizziness | 4.5% | 6.1% | 12.2% | 6% |
| Exertional dyspnoea | 0 | 1.3% | 3.1% | 0.3% |
| Peripheral oedema | 0.7% | 1.3% | 4.4% | 0 |
| Muscle spasms | 0 | 1% | 1.7% | 6.6% |
| Diarrhoea | 1% | 3.7% | 2.7% | 0.7% |
| All adverse events | 15% | 19% | 23% | 23% |
Differences between treatments are statistically significant
more
These figures come from a single trial2 which was not formally included in the NICE evidence review. But it contributed to the recommendations, which were based on expert opinion and current practice.
Published in 2015 and done in the UK, it provides evidence directly applicable to current practice:
A limitation is that the population was relatively “healthy” (average age 61, few co-morbidities) and follow up for each drug was short, so side effects may be underestimated for other population groups or for long-term treatment.
References
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019. (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
2)Williams B, MacDonald TM, Morant S et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386(10008): 2059-2068
Information on treatment harms comes from older RCTs and a more recent observational study.
Both have their limitations but are presented here as a guide.
RCTs: Likelihood of withdrawal from treatment due to side effects from BP-lowering treatment over a 5 year period:
| Placebo | Drug treatment | Absolute Risk Increase | Number Needed to Harm |
| 3% | 14.4% | 11.4% | 9 |
The treatments being used were propranolol, bendroflumethiazide and methyldopa.
From: Cochrane review of drug treatment for mild hypertension1
Evidence quality rated as MODERATE because:
Observational study: rates of specific side effects from BP-lowering treatment over a 6-year period (all drug classes combined) in people at low cardiovascular risk.
Evidence quality rates as LOW because of the nature of the study, but its findings are well worth considering as the design is so relevant to general practice.
| Outcome | Not prescribed treatment | Prescribed treatment | Absolute Risk Increase* | Number Needed to Harm over 10 years** |
| Hypotension | 0.8% | 1.4% | 0.6% | 41 |
| Syncope | 2.5% | 3.2% | 0.7% | 35 |
| Acute kidney injury | 0.8% | 1.0% | 0.2% | 91 |
| Electrolyte abnormality | 0.3% | 0.5% | 0.2% | 111 |
| Falls | No increased risk found | |||
*Absolute risk increases are after a median follow up of 5.8 years. ** Figures calculated by the researchers.
These figures represent events recorded as clinical codes in GP or hospital records.
Click below for more details on the trial.
more
This study showed small absolute rates of harms (because this was a young and relatively healthy population), but a significant relative increase compared to no treatment.
How reliable are these findings?
As with all observational research, biases and limitations might affect the results:
Data detail
data from UK GP records from 1998 to 1025
included two groups, about 19,000 patients each
one group had been prescribed BP-lowering treatment within the first year of diagnosis, the other had not
followed up for an average of 5.8 years (up to 15 years)
Study participant characteristics:
Stage 1 hypertension (defined by 3 x BP readings in range), mean BP 145/86mmHg
mean QRISK score 8%
without established CVD, AF, diabetes, CKD
mean age 55, roughly 1/2 women, mix of demographic characteristics
References
1)Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD006742. DOI: 10.1002/14651858.CD006742.pub2
2)
3)Sheppard JP, Stevens S, Stevens R et al. Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients With Mild Hypertension. JAMA Intern Med 2018; 178(12): 1626-1634
Stage 2-3 hypertension means: clinic BP 160/100 or higher.
NICE recommends offering drug treatment to adults with these levels of hypertension regardless of their baseline QRISK.
The extent to which drug treatment reduces an individual’s cardiovascular risk still depends on their baseline risk.
Here, “combined cardiovascular events” means: fatal and non-fatal MI and stroke (but not including angina or TIA), plus hospitalisation or death from heart failure.
Figures derived from a 2019 Cochrane review1:
Reference
1)Musini VM, Tejani AM, Bassett K et al. Pharmacotherapy for hypertension in adults 60 years or older. Cochrane Database of Systematic Reviews 2019, Issue 6. Art. No.: CD000028
| This research provides a good indication of the treatment effect.
There is a moderate possibility that the true effect is smaller or greater. |
Cochrane rated this evidence as MODERATE quality1.
Although the data was derived from:
there is some uncertainty about the results because of
Reference
1)Musini VM, Tejani AM, Bassett K et al. Pharmacotherapy for hypertension in adults 60 years or older. Cochrane Database of Systematic Reviews 2019, Issue 6. Art. No.: CD000028
The population characteristics in this systematic review of 16 trials 1 were:
* These two trials contributed less than 1% of participants to the overall analysis.
Reference
1)Musini VM, Tejani AM, Bassett K et al. Pharmacotherapy for hypertension in adults 60 years or older. Cochrane Database of Systematic Reviews 2019, Issue 6. Art. No.: CD000028
3 drug classes have the strongest evidence regarding cardiovascular outcomes:
First-line treatment
NICE recommends which of these to choose as first line for particular groups of people1:
more
However, the difference in outcomes between these three classes is not great. Some details here:
more
A 2018 Cochrane review2 provides figures for the relative risk reduction of different outcomes using different drug classes as first-line treatment.
CCBs show the best relative risk reduction for stroke, although the evidence is less certain than for low-dose thiazides.
| Low-dose thiazide | CCB | ACEi | |
| Stroke | 32% (23-40%) | 44% (18-59%) | 35% (18-48%) |
| CHD events | 28% (16-39%) | 23% (n/s) | 19% (6-30%) |
| Total mortality | 11% (3-18%) | 15% (n/s) | 17% (5-28%) |
| Evidence quality | High | Low* | Moderate/Low** |
Relative risk reductions (with 95% confidence intervals) on outcomes by drug class
n/s, not statistically significant
* Rated low quality as only one trial and wide confidence intervals. ** Rated moderate/low quality as wide confidence intervals and some risk of bias
Second- and third-line treatments
The three drug classes can be combined in any order.
Other drug classes: see the “Resistant Hypertension” button.
References
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019 . (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
2)Wright JM, Musini VM, Gill R. First‐line drugs for hypertension. Cochrane Database of Systematic Reviews 2018, Issue 4. Art. No.: CD001841
3)Helmer A, Slater N, Smithgall S. A Review of ACE Inhibitors and ARBs in Black Patients With Hypertension. Ann Pharmacother 2018; 52(11): 1143-1151
A target of below 140/90mmHg (clinic reading) is recommended for most people.
For those aged 80 and over, NICE recommends 150/90mmHg, and to use clinical judgement for those with frailty and multimorbidity1.
Evidence reviews by NICE in 2019 and Cochrane in 2020 found no benefit from treatment to lower targets1,2.
more
NICE reviewed 3 RCTs including 12,559 patients:
No convincing evidence of benefit was found from more intensive treatment.
Cochrane reviewed 11 RCTs including 38,688 patients:
No convincing evidence of benefit was found from more intensive treatment.
What about the SPRINT study? Didn’t that show benefit from low BP targets?
more
This US study, published in 2015, generated a lot of publicity and is cited by many as evidence to support lower BP targets.
It was included in both the NICE and Cochrane reviews described above, though was judged to have important limitations.
What did the study do?
What were the headline results?
| Benefits | Absolute Risk Reduction | Number Needed to Treat | Relative Risk Reduction |
| Total mortality | 1.2% | 85 | 26% |
| Heart failure | 0.8% | 123 | 38% |
| Harms | Absolute Risk Increase | Number Needed to Harm | Relative Risk Increase |
| Acute kidney injury/ acute renal failure | 1.8% | 56 | 70% |
| Serious electrolyte abnormality | 1% | 100 | 37% |
| Serious hypotension | 1.4% | 72 | 70% |
| Serious syncope | 1.1% | 93 | 44% |
So at face value, the trial seems to show a small but important benefit in overall mortality, but at the cost of hospital visits with serious side effects (there’s no data on primary care visits or side effects experienced at home).
What are the criticisms of this trial?
Though the trial was large and of high quality, there were some particular features which may affect its applicability:
Conclusion?
This study may provide evidence that the lower blood pressure target has benefit, but this is uncertain and comes at a significant risk of harm.
For patients who are keen to reduce their cardiovascular risk as much as possible, are at low risk of side effects and who can be adequately monitored, a lower target might be appropriate.
References
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019 . (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
2)Arguedas JA, Leiva V, Wright JM. Blood pressure targets in adults with hypertension. Cochrane Database of Systematic Reviews 2020, Issue 12. Art. No.: CD004349
3)The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015; 373: 2103-2116
Of the combined cardiovascularevents, how many are MIs, how many are strokes and how many are deaths?
This varies depending on age and sex, the numbers below are intended to be a rough guide only:
These two examples use very approximate numbers to give you an idea:
Data detail
For their Lipid guideline in 2019, NICE conducted a health economic analysis which used figures for proportions of first CV events in people of varying ages. These numbers were used to estimate the proportion of CV events in someone at a 40% baseline risk. Then the relative risk reduction of blood pressure treatment1 on each event was calculated. A similar method was used to develop the NICE statin decision aid2.
References
1)Brunström M, Carlberg B. Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis. JAMA Intern Med 2018; 178(1): 28–36
2)Patient decision aid: user guide for healthcare professionals. Implementing the NICE guideline on lipid modification(CG181). [Internet]. [London]: NICE; 2014 Accessed Mar 2021
Resistant hypertension means: hypertension which is uncontrolled despite treatment with 3 classes of drugs (ACEi or ARB+CCB+thiazide).
NICE suggests 3 additional drug classes to consider in addition1:
These have no or very limited evidence of benefit on cardiovascular outcomes, but do lower blood pressure.
BP-lowering effect of these drugs in patients with resistant hypertension already on standard treatment:
| Spironolactone 25-50mg | Bisoprolol 5-10mg | Doxazosin 4-8mg | |
| Mean difference in SBP compared to placebo over 12 weeks | -8.7 mmHg | -4.2 mmHg | -4.6 mmHg |
Side effect rates of these drugs seen in this trial:
| Placebo | Spironolactone 25-50mg | Bisoprolol 5-10mg | Doxazosin 4-8mg | |
| Dizziness | 4.5% | 6.1% | 12.2% | 6% |
| Exertional dyspnoea | 0 | 1.3% | 3.1% | 0.3% |
| Peripheral oedema | 0.7% | 1.3% | 4.4% | 0 |
| Muscle spasms | 0 | 1% | 1.7% | 6.6% |
| Diarrhoea | 1% | 3.7% | 2.7% | 0.7% |
| All adverse events | 15% | 19% | 23% | 23% |
Differences between treatments are statistically significant
more
These figures come from a single trial2 which was not formally included in the NICE evidence review. But it contributed to the recommendations, which were based on expert opinion and current practice.
Published in 2015 and done in the UK, it provides evidence directly applicable to current practice:
A limitation is that the population was relatively “healthy” (average age 61, few co-morbidities) and follow up for each drug was short, so side effects may be underestimated for other population groups or for long term treatment.
References
1)National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management[Internet]. [London]: NICE; 2019 . (NICE guideline [NG136]). Available from: https://www.nice.org.uk/guidance/ng136
2)Williams B, MacDonald TM, Morant S et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386(10008): 2059-2068
There is uncertainty about the rates of side effects from BP treatments.
RCTs vary in how they report harms, and tend to involve people who are at lower risk of harms to start with. These numbers should be viewed as a guide only.
Likelihood of withdrawal from treatment due to side effects from BP-lowering treatment over a 5 year period:
| Placebo | Drug treatment | Absolute Risk Increase | Number Needed to Harm |
| 5.4% | 15.7% | 10.3% | 10 |
From: Cochrane review (2109) of BP treatment in adults over 60 across all ranges of BP severity1
Evidence quality rated as LOW because
Rates of specific side effects from BP-lowering treatment over a 3 year period:
| Outcome | Placebo or less intense treatment | Treatment or more intense treatment | Absolute Risk Increase | Number Needed to Harm |
| All drug classes combined | ||||
| Hypotension | 3.3% | 6.1% | 2.7% | 36 |
| Syncope | 1.1% | 1.3% | 0.2% | 500 |
| Acute kidney injury | 1.5% | 2.1% | 0.6% | 171 |
| Falls | No increased risk found | |||
| ACE inhibitors and angiotensin receptor blockers (ARBs) | ||||
| Hyperkalaemia | 3.0% | 4.8% | 1.8% | 54 |
| Acute kidney injury | 1.1% | 1.5% | 0.4% | 250 |
| Thiazide diuretics | ||||
| Hypokalaemia | 0.8% | 8.2% | 7.4% | 13 |
| Gout* | 0.2% | 2.0% | 1.7% | 58 |
* The estimates for gout risks with thiazide diuretics were not quite statistically significant though probably represent a true effect
From: a systematic review of trials of drug treatment vs placebo AND intense treatment v less intense treatment across all ranges of BP severity2.
Evidence quality rated as VERY LOW because:
References
1)Musini VM, Tejani AM, Bassett K et al. Pharmacotherapy for hypertension in adults 60 years or older. Cochrane Database of Systematic Reviews 2019, Issue 6. Art. No.: CD000028
2) Association between antihypertensive treatment and adverse events: systematic review and meta-analysis
People who have an adverse event
People whose adverse event is prevented by treatment
People who were never going to have an adverse event anyway
Graphics and NNTs are rounded to the nearest integer
These three statistical terms offer three different ways of looking at the results of trial data.
Absolute Risk Reduction
This tells you how many people out of 100 who take a treatment have an adverse event prevented.
MoreThe value of the ARR changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the greater the absolute chance of benefit.
You need to think about over what time the trial data show this benefit, as it is usually assumed that more absolute risk reduction is gained over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Number Needed to Treat
This tells you how many people need to take the treatment in order for one person to avoid an adverse event.
The lower the number, the more effective the treatment.
MoreThe value of the NNT changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the smaller the NNT.
You need to think about over what time the trial data show benefit, as it is usually assumed that more benefit is gained over time and therefore the NNT will drop over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Relative Risk Reduction
This tells you the proportion of adverse events that are avoided if the entire population at risk is treated.
MoreThe value of the RRR is usually constant in people (or populations) at varying degrees of risk.
It is also usually assumed to stay constant over time.
This can be helpful, especially when thinking about population outcomes, but can be misleading for an individual person:
For example, a RRR of 25% in someone with a baseline risk of 40% would give them an ARR of 10% and an NNT of 10.
A RRR of 25% in someone with a baseline risk of 4% would give them an ARR or 1% and an NNT of 100.
This website is designed for use by General Practitioners and other healthcare professionals. The content is not exhaustive and assumes a standard level of GP professional knowledge. The information here is intended to support clinical judgement and shared decision making alongside clinical guidelines and standard practice.
If you are a patient/member of the public, do feel free to look around, but please don’t make any changes to your treatments based on information here. If you find something which seems relevant to you, you could show this website to your healthcare professional to help a discussion.