Download KINES Rapid Update BP lowering Feb 16

Keele’s ‘Important News and Evidence’ Service
KINES
Rapid Update
February 2016
Hypertension: Lowering blood pressure can work whatever the blood pressure
A new comprehensive systematic review and meta-analysis has looked at large-scale, blood pressure lowering trials
published over the last 50 years, comparing outcomes by baseline blood pressures, the amount of blood pressure
lowering, and the type of drug used. The findings support the perspective that the lower the blood pressure, the better;
those with established cardiovascular disease or high cardiovascular risk have most to gain. Cardiovascular harm was
not increased by achieving very low blood pressure.
Reference: 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. 2015; (published online Dec 23.)
http://dx.doi.org/10.1016/S0140-6736(15)01225-8.
What do we already know?
Traditionally blood pressure has been categorised as either ‘high’ or ‘normal’, and guidelines recommend
treatment for those in whom blood pressure is over a certain threshold. For example, the NICE guideline on
hypertension (NICE CG127) suggests treatment if clinic blood pressure is 140/90 mmHg or higher (with
subsequent ambulatory or home blood pressure monitoring averaging 135/85 mmHg or higher) in those with high
cardiovascular risk.
In recent years, blood pressure guidelines have relaxed blood pressure treatment targets. For example, for most
people, NICE CG127 sets a target clinic systolic blood pressure (SBP) of 140 mmHg.
The SPRINT study recently reported benefits from lowering SBP to below 120 mmHg, although as pointed out in
the December 2015 KINES Rapid Update1 discussing this study, the absolute benefits of additional lowering are
marginal in people at low risk of cardiovascular disease.
Trials of blood pressure drugs do not usually include older people; although older people generally benefit from
treating hypertension, care is still needed when using these drugs in frail people and those with several comorbidities. In particular, the risk of falls is a serious concern (Tinetti et al, 2014). Such harms may be a particular
issue if treating at, or to, low blood pressure levels.
Alongside these trials of blood pressure drugs, it is important to recognise the role that eating healthily, taking
more physical activity, reducing alcohol intake and maintaining a healthy weight, have in reducing blood pressure.
Other components to consider in supporting people in management of blood pressure are the place of shareddecision making and patient decision aids.
What does this new evidence add?
Blood pressure lowering significantly reduces vascular risk across all the various baseline blood pressure levels
and comorbidities.
No J-shaped curve was seen – that is, no additional cardiovascular harm was seen in lowering systolic blood
pressure (SBP) to less than 130 mm Hg. Other adverse events could not be evaluated in this analysis.
The higher the risk of cardiovascular disease the more the absolute benefit to be gained by blood pressure
lowering treatment. This may indicate a move away from arbitrary thresholds of blood pressure to trigger initiation
of treatment in higher risk people in future.
In particular, these results support the consideration of blood pressure lowering treatment in all individuals with a
history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney
disease, whatever their blood pressure.
This is similar to lipid modification with statins, where NICE guidance now supports a strategy based on evidence
that the absolute benefit is determined by the overall level of cardiovascular risk, rather than a threshold level for
cholesterol.
This study did not analyse effects of blood pressure drugs by age and only a few of the included studies involved
subjects with a mean age greater than 70 years.
1
* This and other KINES Rapid Updates are available by login at www.centreformedicinesoptimisation.co.uk
Study details:
Participants:
A literature search (MEDLINE only) was conducted, searching between 1966 and July 2015, to identify
randomised controlled trials (RCTs) of blood pressure lowering treatment. Further trials were included if published
before 9th November 2015.
All trials were selected that had a minimum of 1000 patient-years of follow-up for each treatment group –
described as ‘large-scale’ trials. These included trials using antihypertensives for indications other than blood
pressure. However, the authors excluded trials in populations with heart failure or left ventricular systolic
dysfunction from the main standardised analyses, due to the effects of antihypertensives on achieved blood
pressure in heart failure varying substantially with baseline blood pressure within a trial population.
123 studies with 613,815 participants were included for the meta-analysis. 113 studies were judged to be of low
risk of bias; the risk of bias was unclear in 10.
One of the RCTs included was the recent SPRINT study.
Intervention and Comparison:
Eligible studies were categorised into 3 groups:
o random allocation of patients to a blood pressure lowering drug or placebo (78 trials).
o random allocation of patients to different blood pressure lowering drugs (43 trials).
o random allocation of patients to different blood pressure lowering targets (14 trials).
o Some of the studies fell in several categories
Outcomes and results:*
Meta-regression analyses showed relative risk reductions for major cardiovascular disease events (p < 0·0001),
stroke (p < 0·0001), heart failure (p < 0·0001), and all-cause mortality (p = 0·014) to be proportional to the
magnitude of the blood pressure reduction achieved. The meta-regression results were not significant for coronary
heart disease (p = 0·058) or renal failure (p = 0·09).
No significant trend towards increased risk of cardiovascular harm was reported for any outcome (major
cardiovascular events, coronary heart disease, stroke, heart failure, renal failure or all-cause mortality) based on
different baseline SBPs.
Every 10 mm Hg reduction in SBP significantly reduced the risk of:
o Major cardiovascular disease events (relative risk 0·80, 95% confidence interval 0·77–0·83).
o Coronary heart disease (0·83, 0·78–0·88).
o Stroke (0·73, 0·68–0·77).
o Heart failure (0·72, 0·67–0·78).
o All-cause mortality (0·87, 0·84–0·91).
The effect on renal failure was not significant (0·95, 0·84–1·07).
Similar proportional risk reductions (per 10 mm Hg lower SBP) were noted in trials with higher mean baseline SBP
and trials with lower mean baseline SBP (all ptrend>0·05).
Proportional risk reductions were similar for baseline disease history, except for diabetes and chronic kidney
disease, for which smaller, but significant, risk reductions were detected.
Overall, all of the drug classes used for initial therapy demonstrated similar levels of effectiveness. For individual
outcomes:
o Beta-blockers were statistically inferior to other drugs for the prevention of major cardiovascular disease
events (1.17, 1.11-1.24), stroke (1.24, 1.14-1.35), and renal failure (1.19, 1.05-1.34); but, the difference in
all-cause mortality was not statistically different (1.06, 1.01-1.12).
o Calcium channel blockers were superior to other drugs for the prevention of stroke (0.90, 0.85-0.95).
o For the prevention of heart failure, calcium channel blockers (1.17, 1.11-1.24) were inferior and diuretics
were superior to other drug classes (0.81, 0.75-0.88).
However, this study does not examine the effects of combinations of blood pressure lowering drugs, which are
now in common use.
Level of evidence: Level 1 (good quality patient-orientated evidence) according to the SORT criteria.
Study funding: Funded by the National Institute for Health Research and Oxford Martin School (not commercially
funded).
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