ADVANCE analysis fuels debate on BP targets in type 2 diabetes
medwireNews: A post-hoc analysis of the ADVANCE trial indicates that people with type 2 diabetes may benefit from additional antihypertensive medications even if their blood pressure (BP) is already below the 140/90 mmHg target.
The findings are published in the wake of ACCORD BP, which showed no additional value for more intensive systolic BP control (120 vs 140 mmHg) in people with type 2 diabetes, contrasting with the more recent SPRINT trial, which showed significant reductions in the risk for cardiovascular disease (CVD) and death with intensive versus standard BP control in people without the condition.
ADVANCE was a different design from these trials in that it compared combination perindopril–indapamide treatment with placebo, rather than treating to specific BP targets. During an average 4.3 years of follow-up of 10,948 participants, all of whom had type 2 diabetes, those receiving the study intervention had a significant 9% reduction in the risk for major CVD events and a 14% reduction in mortality risk, compared with those taking placebo.
There was no evidence that active treatment modified patients’ CVD risk to a different degree according to their baseline systolic BP, down to less than 120 mmHg, report John McEvoy (National University of Ireland, Galway) and co-researchers in Hypertension.
Combined with the fact that on-treatment systolic BP remained below 130 mmHg throughout follow-up in participants with baseline levels below 140 mmHg, this suggests continued benefit in diabetes patients who had achieved tighter BP control.
Speaking to medwireNews, Ian de Boer (University of Washington, Seattle, USA), lead author of the ADA 2017 Position Statement on hypertension, said that “it is fair and important to draw some information from [ADVANCE] and extrapolate it to blood pressure targets.”
He stressed that “it is a different intervention, and I don’t think these data necessarily help us reconcile SPRINT and ACCORD,” but said that “it does suggest that, at least in some people with type 2 diabetes, going to lower blood pressure is beneficial.”
de Boer noted that in fact the ACCORD data “give some signal of that too, with the benefit on stroke, the secondary outcome, so I think it does lend some support there.”
He said: “Ultimately I think it would be good to combine individual data for a number of blood pressure lowering studies in type 2 diabetes to do this sort of analysis with larger numbers and larger power.”
ADVANCE was not powered to assess benefit in subgroups of different baseline BPs, and de Boer also observed that baseline BPs were based on two readings at one timepoint, increasing the risk for misclassification due to natural BP variability over time.
However, notwithstanding these caveats, he noted a possible greater benefit of active treatment in patients with a baseline 10-year atherosclerotic CVD risk of at least 20%. For the outcome of major vascular events, this higher risk group had a significant 9% risk reduction, compared with no effect in the lower risk group. The difference between the treatment effects in the two groups did not quite attain statistical significance, with a p value of 0.08.
This “certainly is not conclusive evidence that there is a difference in risk by baseline atherosclerotic cardiovascular risk,” said de Boer. “But it sure looks like it.”
He also stressed the importance of considering absolute CVD risk, because higher baseline risk equates to a larger absolute risk reduction. Among patients with baseline systolic BP of at least 140 mmHg, for example, those with high CVD risk had a reduction from 19.3% to 17.6% with placebo versus active treatment, compared with respective rates of 13.0% and 13.7% in the lower risk group. The same was true for all-cause mortality.
By contrast, the adverse effects of intensive BP control did not differ with baseline BP or CVD risk, either in this study or in SPRINT or ACCORD. This therefore suggests a larger benefit-to-risk balance for people with high CVD risk, noted de Boer.
“The implication of that is that when one individualizes blood pressure targets it is important to consider absolute benefits and absolute risks, as people with high absolute risk of cardiovascular disease are more likely to derive benefit from intensive control,” he said.
De Boer said he would like to see more research to help guide individualization of BP treatment, “so coming up with ways to identify the participants in studies, the patients in our practice who are most likely to benefit and least likely to have harm.”
He said: “I think there is room still to move forward with this kind of precision medicine approach, and I think that would help refine guidelines, directing providers and patients as how best to target intensive blood pressure control.”
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