Analysis Supports Aiming for Lower BP in Patients With Diabetes, Hypertension

Patients with type 2 diabetes benefit from having their blood pressure lowered below 130/80 mm Hg, regardless of baseline BP or estimated 10-year risk of atherosclerotic CVD, a post hoc look at the ADVANCE trial suggests.

Reductions in major vascular events and all-cause mortality with a fixed combination of perindopril and indapamide versus placebo did not vary based on those factors, as demonstrated by nonsignificant P values for heterogeneity, investigators led by Faisal Rahman, MBBS (Johns Hopkins University, Baltimore, MD), report.

The findings, according to study author John McEvoy, MBBCh (National University of Ireland, Galway), provide support for the comprehensive hypertension guideline released in November 2017 by the American College of Cardiology (ACC), the American Heart Association (AHA), and nine partnering organizations. In it, the guideline writers recommend treating all adults with diabetes and hypertension to a goal of less than 130/80 mm Hg, lowering the goal compared with prior guidance based primarily on the results the SPRINT trial.

The US guideline, which applies that treatment goal to most patients with hypertension, goes further than other major recommendations, however. For instance, in its recently updated standards of care, the American Diabetes Association (ADA) recommends treating patients with a lower risk for CVD to a goal below 140/90 mm Hg, saying the stricter goal of less than 130/80 mm Hg “may be appropriate, if it can be safely attained” in those with a higher risk.

The European Society of Cardiology is also more conservative than the ACC/AHA in its 2018 hypertension guideline, saying that the systolic BP goal in patients with diabetes should be 130 mm Hg; lower goals should be considered if the treatment is well tolerated, but values below 120 mm Hg should be avoided.

McEvoy said this new analysis of ADVANCE, published online April 29, 2019, ahead of print in Hypertension, “would be more consistent with the current US guideline.”

The Diabetes Dilemma

As illustrated by the inconsistencies between guidelines, the optimal BP goal for patients with diabetes and hypertension remains controversial. Matters have not been helped by the discrepant results from the SPRINT and ACCORD trials. Both randomized patients to intensive BP control (to a systolic goal of less than 120 mm Hg) or standard control (less than 140 mm Hg), with SPRINT enrolling high-risk patients without diabetes and ACCORD enrolling diabetic patients. Only SPRINT showed a significant reduction in adverse clinical outcomes with intensive control.

The differing results “created somewhat of a dilemma, I would say, because we all consider diabetics to be at high risk for cardiovascular disease. . . . It was challenging to know what to do with diabetics in the context of SPRINT and ACCORD, put side by side,” McEvoy said.

It was challenging to know what to do with diabetics in the context of SPRINT and ACCORD, put side by side. John McEvoy

He noted that some observers felt that ACCORD was underpowered and that the lower BP goal should be considered for patients with diabetes. That thought was ultimately adopted in the US guideline.

In that context, McEvoy said his group thought it would be informative to see whether patients with type 2 diabetes in the ADVANCE trial who already had a systolic reading below 140 mm Hg at baseline would derive a benefit from additional BP-lowering with perindopril-indapamide. The trial included patients with type 2 diabetes and either a history of CVD or risk factors for disease.

Mirroring the main trial results released in 2007, the investigators found that the antihypertensive combination reduced risks of all-cause mortality (HR 0.86; 95% CI 0.75-0.99) and major vascular events (HR 0.91; 95% CI 0.83-0.997) through a mean follow-up of 4.3 years.

Those reductions were consistent across baseline systolic BP strata ranging from less than 120 mm Hg to 160 mm Hg or more (P for heterogeneity = 0.49 for all-cause mortality and 0.85 for major vascular events). Baseline diastolic pressure (ranging from less than 70 mm Hg to 90 mm Hg or higher) and estimated 10-year CVD risk (less than 20% versus 20% or more) also did not significantly modify the benefits of treatment.

Moreover, although discontinuation due to cough or hypotension/dizziness was more frequent with active treatment, the effect did not vary according to baseline BP or estimated CVD risk.

Time to Be Less Conservative?

McEvoy said the post hoc analysis of ADVANCE “gives some justification to the lower target that the 2017 [ACC/AHA] guidelines endorsed,” and suggests other guideline-writing bodies—who have already started moving toward lower goals—should be less conservative.

Still, physicians should use caution when taking BP below 130/80 mm Hg in their patients with diabetes, who tend to have more advanced vascular disease and stiffer arteries, he said. In that situation, there is a risk of the diastolic pressure dropping too low, and care should be taken to not allow the diastolic reading to go below 60 mm Hg, he explained.

“If you really drop the diastolic pressure significantly you may reduce blood flow into the coronary arteries during diastole, which could lead to ischemia,” McEvoy said. That caveat pertains to all patients with hypertension, but because patients with diabetes tend to have stiffer arteries, it is “a significant clinical consideration for diabetics,” he added.

Commenting for TCTMD, George Bakris, MD (University of Chicago, IL), who chaired the committee that wrote a 2017 ADA position paper on diabetes and hypertension, was skeptical about the study authors’ conclusion that this analysis from ADVANCE bolsters the US guidance. The analysis was limited by its post hoc nature, the fact that the ADVANCE results came out more than a decade ago, and the fact that the trial was not designed to compare different levels of BP control, Bakris said.

Moreover, even though the new data show no significant effect modification according to baseline BP, that’s actually supportive of more traditional BP goals by showing that patients who attained lower levels of BP during the trial did not do any better than those who came in under 140/90 mm Hg, Bakris said.

“My assessment of this is consistent with a number of other meta-analyses that have been done of a variety of trials that basically show that reducing blood pressure to less than 140 mm Hg gives you great results and going to less than 130 mm Hg doesn’t give you any greater benefit,” he said. “All this is telling you is that if you go below 130 mm Hg you’re still getting a benefit. It’s not a greater benefit.”

Bakris also pointed to prior studies that have suggested that taking systolic BP too low in patients with diabetes—below about 120 to 125 mm Hg—increases the risks of adverse outcomes, including CV death; that relationship was not seen in patients without diabetes. The increased risk probably has to do with the small-vessel disease characteristic of advanced diabetes, he explained.

“So there needs to be some balance here, and that’s why we tried to do that in the ADA guidelines,” said Bakris, noting that in his practice he aims to have patients in the systolic BP range of 128 to 135 mm Hg. “I think they went overboard in the ACC/AHA guidelines.”