Review: Intensive Blood-Pressure Lowering Improves Outcomes

Miriam E Tucker

November 06, 2015

Intensive blood-pressure reduction below currently recommended targets provides greater vascular protection, particularly for people at high risk for cardiovascular outcomes, the results of a new systemic review and meta-analysis suggest.

The findings were published online November 6 in the Lancet by Dr Xinfang Xie, of the renal division, department of medicine, Peking University First Hospital, Beijing, China, and colleagues.

The review, of 19 trials involving nearly 45,000 participants, showed that intensive blood-pressure lowering achieved in the trials significantly reduced major cardiovascular events (composite), stroke, myocardial infarction (MI), albuminuria, and retinopathy progression, but had no impact on heart failure, cardiovascular death, total mortality, or end-stage kidney disease compared with less intensive regimens.

The new data call into question the recent loosening of blood-pressure targets for some high-risk populations in recent guidelines from the Eighth Joint National Committee (JNC8) and the European Society of Cardiology/European Society of Hypertension among others, Xie and colleagues say.

"This review and meta-analysis provides clear evidence of the benefits of more intensive blood-pressure lowering, including in high-risk patients whose systolic blood pressure is lower than 140 mm Hg. Existing clinical guidelines should be revised accordingly, to recommend more intensive blood-pressure–lowering treatment in high-risk patient groups," the authors write.

The paper was published on a "fast-tracked" basis ahead of the American Heart Association 2015 Scientific Sessions that begins on November 7, 2015 in Orlando, Florida. On November 9, results of an additional trial showing benefit of intensive blood-pressure lowering, the National Institutes of Health-sponsored Systolic Blood Pressure Intervention Trial (SPRINT), will be presented.

Top-line SPRINT results released in September showed that treating high-risk hypertensive adults 50 years of age and older to a systolic target of 120 mm Hg significantly reduced cardiovascular events by 30% and reduced all-cause mortality by nearly 25% when compared with patients treated to a target of 140 mm Hg.

That study, which included hypertensive patients with one additional cardiovascular risk factor or preexisting kidney disease, was stopped earlier than the planned 2018 completion date because of the benefit of the intensive strategy, according to investigators.

In an editorial, Drs Mattias Brunström and Bo Carlberg, both of the department of public health and clinical medicine, division of medicine, Umeå University, Sweden, caution that while the current systemic review/meta-analysis "is the most comprehensive compilation" so far of trials comparing different blood-pressure targets, "the results of the review still do not represent all the available evidence for blood-pressure lowering."

Because the review only included small numbers of trials specifically looking at elderly patients and those with diabetes, Brunstrom and Carlberg question whether there is sufficient evidence to change guidelines for those and other high-risk patient groups. They point to the upcoming SPRINT data as a likely source of further information.

Significant Benefit With Intensive Treatment for High-Risk Groups

The 19 trials included a total 44,989 participants, among whom there were 2496 major cardiovascular events (in 14 studies), 1762 all-cause deaths (19 studies), and 514 end-stage kidney disease events (eight studies). All of the trials were open-label, with a mean follow-up of 3.8 years (range, 1–8).

As the editorialists noted, the trials were heterogeneous in both their study populations and blood-pressure targets. Five trials enrolled patients with diabetes, while six focused specifically on those with chronic kidney disease and two enrolled elderly patients.

Most of the trials (17) enrolled patients with preexisting hypertension and vascular disease, kidney disease, diabetes, or other risk factors.

Blood-pressure targets varied across the trials. The mean levels actually achieved were 133/76 mm Hg in the intensive-treatment groups vs 140/81 mm Hg in the control arms.

From the 14 trials of 43,483 participants investigating major cardiovascular event rates (2496 events total), the more intensive blood-pressure–lowering regimens significantly reduced the risk by 14% compared with less intensive regimens. From 13 trials including 42,389 participants, the risk of MI (864 total events) was reduced by 13%, and from 14 trials of 43,483 participants, stroke (1099 total events) was reduced by 22%.

More intensive blood-pressure control also reduced the risk of albuminuria (three trials, 5224 participants, 1924 events) and progression of retinopathy (four trials, 2665 participants, 693 events), although there was substantial heterogeneity across the latter trials.

In contrast, no significant reductions were seen with intensive blood-pressure lowering in heart failure (10 trials with 33,306 subjects and 410 occurrences), or end-stage kidney disease outcomes (eight trials, 8690 participants, 514 events).

The investigators also found no clear evidence of an effect of intensive blood-pressure lowering on cardiovascular or noncardiovascular death.

The greatest effect of intensive blood-pressure lowering was seen in the trials in which all patients had vascular disease, renal disease, or diabetes at baseline. Here, the average control-group rate of major vascular events was 2.9% per year compared with 0.9% per year in other trials, and the numbers needed to treat were 94 in these trials vs 186 in all other trials.

Adverse-event reporting was inconsistent across the trials. In six trials that did report severe adverse events (12,265 participants, 491 events), there was no clear difference between the treatment groups.

Among five trials that reported severe hypotension outcomes involving a total 10,089 participants, the risk was nearly tripled with the intensive-treatment regimen (61 vs 23 events, P = .015). More intensive blood-pressure control also resulted in more dizziness (five trials, 9778 participants, 1125 events).

Finally, the rate of drug discontinuation did not differ between the more intensively and less intensively treated groups in the four trials that reported those data (9665 participants, 343 events).

"In patient populations at high risk of vascular disease, the absolute benefits of treatment will comfortably surpass the absolute harms," Xie and colleagues write.

Indeed, Brunstrom and Carlberg say, "Xie and colleagues' systematic review provides strong evidence that intensive blood-pressure reduction is more beneficial than less intensive blood-pressure reduction. This finding will pave the way for the treatment of a large number of additional patients compared with the number treated at present."

However, they also caution, "It is not yet obvious that patients with diabetes mellitus or very elderly patients will benefit from lower treatment targets than the recommended goal of lower than 140/90 mm Hg. Thus, the definition of new blood-pressure–treatment targets will not be an easy task, in terms of comorbidity and a specific mm-Hg target."

The study was funded by National Health and Medical Research Council of Australia. Dr Xie has no relevant financial relationships; disclosures for the coauthors are listed in the paper. Brunstrom and Carlberg have no relevant financial relationships.

Lancet. Published online November 6, 2015. Article, Editorial


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