Cardiovascular Journal of Africa: Vol 30 No 2 (March/April 2019)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 2, March/April 2019

AFRICA

However,

post hoc

analysis of achieved BP in clinical trials is

subject to reverse causality and unrecognised confounders. No

single trial provides a clear answer and the evidence should be

looked at in totality.

Several systematic reviews have been performed related to this

topic. They vary in the exact question addressed and whether

they include data from SPRINT. As a group they provide useful

insights, although not necessarily definitive answers.

When comparing information from these sources it is worth

remembering that individual trials and reviews do not have

entirely consistent definitions of endpoints and vary in selected

duration of treatment and follow up. Definitions of what

constitutes primary prevention (versus treatment in the presence

of co-morbidities) also vary. Some reviews focused on initial

treatment thresholds, whereas others looked at achieved target

levels.

One of the earliest post-SPRINT reviews was that by Ettehad

et al

a review of 123 studies with 613 815 participants. Overall,

a 10-mmHg reduction in systolic BP reduced the risk of major

cardiovascular disease events by 20%, coronary heart disease

by 17%, stroke by 27%, heart failure by 28%, and all-cause

mortality by 13%. Specifically, the all-cause mortality benefit

was also seen in the stratum with baseline BP

130 mmHg, and

this information has been used as evidence to support a tighter

treatment threshold.

In this generally well-conducted systematic review, several

issues warrant attention. Heterogeneity was moderate for some

outcomes (e.g. the

statistic for the composite endpoint of

major cardiovascular events was 41%). For BP

130 mmHg,

there is almost an outlier effect with consistently larger benefit in

this group, but with wide confidence intervals (CI) reflecting the

small absolute number of events in this group. For example, in

the mortality endpoint group, only 4.1% (410/9 998) of events in

the control arm occurred in the group with BP

130 mmHg. The

conclusions around this group are hence considerably less robust,

and probably mostly driven by SPRINT. A final point is that the

method of standardisation used in the review may have affected

study weights and increased the size of treatment effects.

A more recent review was published in 2018

using slightly

different methodologies. In this review (74 trials, 306 273

participants), overall benefits across the different outcomes was

satisfyingly consistent with the previous article. In this review, the

only group where starting BP

140 mmHg was associated with

any statistically significant benefit was for heart failure [relative

risk reduction (RRR) 0.88, 95% CI: 0.78–0.98].

An earlier systematic review

showed broadly similar results,

although it was published before SPRINT. For the intensive-

therapy group (mean BP 133/76 mmHg), major cardiovascular

events were reduced (RRR 14%, 95% CI: 4–22), as was

myocardial infarction (RRR 13%, 95% CI: 0–24) and stroke

(RRR 22%, 95% CI: 10–32), but without benefit for congestive

cardiac failure (RRR 15%, 95% CI: –11–34) or total mortality

rate (RRR 9%, 95% CI: –3–19).

A network meta-analysis of randomised control trials (17

RCTs, 55 163 patients with 204 103 patient-years of follow

up), including SPRINT, found a benefit of lower systolic BP

targets for reducing stroke and myocardial infarction. There was

no significant difference in rates of mortality, cardiovascular

mortality or heart failure in the

120-mmHg target group when

compared to the higher target groups.

This analysis did not only

look at the benefits of lower BP targets but importantly, also

considered the potential harm and severe adverse events, which

were highest for BP target

120 mmHg.

Conclusion

The results of systematic reviews of more intensive lowering of

BP are discordant, with some differences explained by variations

in methodology. In the review showing apparent clear benefit,

there were criticisms of the mechanism of standardisation, and

the results in the subgroup analysis of those with BP

120 mmHg

showed results with wide confidence intervals due to small

absolute numbers of events. In addition, the relative benefits

in this group were discordantly large and possibly influenced

by SPRINT. In SPRINT, the automated BP-measuring process

may have generated lower readings, allowing for alternative

explanations of the findings such as that the better outcomes,

especially heart failure, may have been due to greater use of

diuretics rather than necessarily the BP target.

It is likely that a tailored approach allowing for more

intensive control of BP in specific high-risk individuals may be

beneficial. Prior to a general introduction of tighter BP targets,

it is important to assess compliance with current targets, as

local evidence mirrors international experience of less than 50%

control in many patients. It is also important to consider the

availability of resources to implement new targets, to ensure

that implementation is safe and feasible. From a public health

perspective, optimising control in current patients, and lifestyle

modification in younger patients may be more appropriate local

interventions.

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