Research shows that treatment with antihypertensive medications in patients with type 2 diabetes and hypertension is effective in reducing the risk for adverse cardiovascular (CV) and renal outcomes.1 However, current guidelines provide varying recommendations for target blood pressure (BP) in this population.1 As new clinical evidence becomes available, the debate over more conservative BP control (systolic BP <120-130 mm Hg) in patients with type 2 diabetes continues.
Endocrinology Advisor discussed the emerging research on this topic with William C. Cushman, MD, FAHA, FACP, chief of the preventive medicine section at the Veterans Affairs Medical Center and professor in the department of preventive medicine, medicine, and physiology at the University of Tennessee Health Science Center, both in Memphis, and Rhonda Cooper-DeHoff, PharmD, MS, FAHA, FACC, FCCP, associate professor and university term professor in the department of pharmacotherapy and translational research and division of cardiovascular medicine at the University of Florida in Gainesville.
Endocrinology Advisor: What were the main goals of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial (ACCORD BP)2 and how were they addressed in the study?
William C. Cushman, MD, FAHA, FACP: ACCORD BP, sponsored by the National Heart, Lung and Blood Institute (NHLBI), was part of a 2´2 factorial study that included BP intervention in 4733 participants out of a total of 10,251 enrolled participants with type 2 diabetes.2 It compared cardiovascular disease (CVD) and other outcomes in 4733 participants randomly assigned to an intensive BP goal group (systolic BP <120 mm Hg) vs standard BP goal group (systolic BP <140 mm Hg), and intensive (glycated hemoglobin [HbA1c] <6.0) vs standard (HbA1c 7.0-7.9) glycemic control (all 10,251 participants). All BP trial participants were also in the glycemia trial and met those eligibility criteria. All major classes of antihypertensive medications were provided and could be used to reach BP goals. The mean systolic BP averaged 119 mm Hg in the intensive BP goal group and 134 mm Hg in the standard BP goal group. The BP trial sample size was based on the assumption that the primary CVD outcome (the composite of nonfatal myocardial infarction, nonfatal stroke, or CVD death) would occur at a 4% annual rate and be reduced by 20% by the intensive intervention.
Endocrinology Advisor: What were the main findings of the ACCORD BP study and their potential long-term implications?
Dr Cushman: After a mean follow-up of 4.7 years, the rate of the primary CVD outcome was only 2.09% per year in the standard BP goal group — the hazard ratio (HR) was reduced by a nonsignificant 12%, but the CI included the predicted 20% benefit (27% reduction to 6% increase in CVD).2 In addition, stroke, a secondary outcome, was reduced by 41% (P =.01) and the primary outcome was reduced by 26% in the standard glycemia group (the intensive glycemic control group had been stopped early because of an increase in mortality).3
Since ACCORD BP was reported in 2010, the Systolic Blood Pressure Intervention Trial (SPRINT) was stopped early in 2015 because CVD and mortality benefit was attained with the same intensive systolic BP goal (<120 mm Hg) in 9361 high-CVD-risk hypertensive participants age ≥50 but without known diabetes.4 In a retrospective analysis of a subgroup of patients with “prediabetes” (glucose ≥100 mg/dl), which did include some participants with glucose levels in the diabetic range, SPRINT found a CVD risk reduction (31%) similar to that in the normal glucose subgroup (17%; P value for interaction 0.30). In other hypertension trials showing the benefits of BP reduction, patients with diabetes usually had the same or greater CVD reduction as patients without diabetes; this has been reported in several meta-analyses.
Therefore, until further data is available, which may not be soon, it seems reasonable to consider a more intensive systolic BP goal (<120 to 130 mm Hg) at least in high-risk hypertensive patients with diabetes. The recent American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline reflects this perspective by recommending a BP goal <130/80 mm Hg in patients with diabetes.5
Endocrinology Advisor: In 2010, your team published a study examining the association between systolic BP control and adverse CV outcomes in patients with type 2 diabetes. 6 What were the main findings of this study?
Rhonda Cooper-DeHoff, PharmD, MS, FAHA, FACC, FCCP: The International Verapamil SR-Trandolapril Study (INVEST) included a total of 6400 patients with diabetes, coronary artery disease, and hypertension.6 All patients were treated with antihypertensive medications and followed for at least 2 years after enrollment in the study. In our analysis, we categorized the patients with diabetes according to their on-treatment systolic blood pressure (SBP) as: (1) tight control if SBP <130 mm Hg, (2) usual control if SBP 130 mm Hg <140 mm Hg, and (3) uncontrolled if SBP was ≥140 mm Hg. We assessed adverse CV outcomes, including the primary outcome, which was the first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke.
We observed similar adverse CV outcomes in the tight control and usual control groups, while patients in the uncontrolled group had a higher risk for outcomes. Of note, when we analyzed the outcome of all-cause death, patients in the tight control group had the highest event rate (11.0%) compared with the usual control group (10.2%), (adjusted HR, 1.20; 95% CI, 0.99-1.45; P =.06); however, when extended follow-up was included, the risk for all-cause mortality was 22.8% in the tight control vs 21.8% in the usual control group (adjusted HR, 1.15; 95% CI, 1.01-1.32; P =.04).
Overall, our data in hypertensive patients with coronary artery disease and diabetes indicate that tight control of systolic BP was not associated with improved CV outcomes compared with usual control.
Endocrinology Advisor: How do these findings correlate with the latest hypertension treatment recommendations?
Dr Cooper-DeHoff: It is important to put our data into perspective with regard to the recommendations. The 2017 ACC/AHA hypertension treatment guideline recommends a treatment goal of <130/80 mm Hg in patients with diabetes.5 The American Diabetes Association, in their Standards of Medical Care in Diabetes–2018,7 recommends that most patients with diabetes and hypertension should be treated to a systolic BP goal of <140 mmHg and a diastolic BP goal of <90 mm Hg (level of recommendation A). They also suggest that lower systolic and diastolic BP targets, such as 130/80 mm Hg, may be appropriate in individuals at high risk for CVD if they can be achieved without undue treatment burden (level of recommendation C).
Endocrinology Advisor: What types of studies still need to be conducted to further examine the association between BP targets and CV outcomes in patients with type 2 diabetes?
Dr Cooper-DeHoff: I am not sure that we need more studies at this time. What we need most of all is for healthcare providers to diligently focus on hypertension as an important comorbid condition that is strongly associated with adverse CV outcomes, including death. There is a lot of room to improve the implementation of strategies to lower BP in general and getting patients to <140/90 is step 1. There is very likely a subset of patients with diabetes and CVD, particularly younger patients who would benefit from even lower BP (<130/80). But providers must pay attention to how patients tolerate their BP-lowering medications and whether they can afford them and remember that there is no one-size-fits-all. Each patient is an individual with specific BP-lowering needs.
Dr Cushman: Since ACCORD BP suggested benefit, especially in the standard glycemia subgroup, but was underpowered overall, and the retrospective analysis of the SPRINT prediabetes subgroup suggested the benefit of more intensive therapy, further trials testing intensive BP-lowering in patients with diabetes are needed to develop class A level of evidence to make definitive recommendations in the treatment of hypertension in diabetes. In addition, more trials are needed in patients with diabetes with chronic kidney disease. In the meantime, I agree that BP should be treated to at least <140/90 mm Hg in these patients with consideration of a further goal <130/80 mm Hg. In patients with diabetes with hypertension and a high burden of comorbidity, clinical judgment and patient preference is reasonable for decisions regarding the intensity of lowering BP.
Mancia G. Effects of intensive blood pressure control in the management of patients with type 2 diabetes mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Circulation. 2010;122(8):847-849.
- ACCORD Study Group, Cushman WC, Evans GW. Effects of intensive blood-pressure control in type 2 diabetes mellitus.N Engl J Med. 2010;361(17):1575-1585.
- Margolis KL, O’Connor PJ, Morgan TM, et al. Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial. Diabetes Care. 2014;37(6):1721-1728.
- SPRINT Research Group. A Randomized trial of intensive versus standard blood-pressure control.N Engl J Med. 2015;373:2103-2116.
- Carey RM, Whelton PK. The 2017 American College of Cardiology/American Heart Association Hypertension Guideline: A Resource for Practicing Clinicians. Ann Intern. Med. 2018;168(5):359-360.
- Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010;304(1):61-68.
- American Diabetes Association. Standards of Medical Care in Diabetes–2018. Arlington, Virginia: American Diabetes Association; 2018.