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Another Look at Blood Pressure Targets for People with Type 2 Diabetes

Jun 16, 2018
 

Discrepancies prompt additional analyses of ACCORD-BP and SPRINT studies to determine best blood pressure for diabetes patients.

When encountering a patient with diabetes and hypertension, two disease states that often go hand in hand with one another, a few essential things must be decided. Are lifestyle modifications enough to eliminate hypertension in this patient? What antihypertensive should be prescribed? And what blood pressure target should they strive for?

Seems easy enough, but deciding on a blood pressure target means deciding which guideline to follow and which best suits your patient. At this time, two guidelines, the American Diabetes Association (ADA) and the American College of Cardiology/American Heart Association (ACC/AHA), exist and both are saying different things. Currently, the ADA recommends most patients be targeted at systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg. But, suggests that people who have diabetes are at high risk for cardiovascular disease (CVD), capable of tolerating more intensive regimens, should strive for SBP target <130 mmHg and DBP <80 mmHg. The ACC/AHA recommends patients with diabetes target the more stringent goal of <130/<80 mmHg.

Why the discordant recommendations? This comes from the conflicting findings published in two widely discussed studies, the Action to Control Cardiovascular Risk in Diabetes–Blood Pressure (ACCORD-BP) and the Systolic Blood Pressure Intervention Trial (SPRINT). Both studies looked at the effect of standard blood pressure lowering (<140 mmHg) or stringent antihypertensive regimens (<120 mmHg) on cardiovascular outcomes in those with type 2 diabetes (ACCORD-BP) and those without (SPRINT). The ACCORD-BP trial concluded that a more intensive blood-pressure–lowering target, <120 mmHg, did not reduce rates of fatal and nonfatal cardiovascular events in those with type 2 diabetes [HR with intensive treatment, 0.88 (95% CI 0.73-1.06; p = 0.20)]. Conversely, the SPRINT research group found significantly lower rates of fatal and nonfatal cardiovascular events in patients without diabetes treated with a more stringent blood pressure target of <120 mmHg [HR with intensive treatment, 0.75 (95% CI 0.64-0.89; p < 0.001).

Although both studies investigated mostly similar primary composite outcomes (i.e. nonfatal myocardial infarction or stroke, CVD death), follow-up analyses of both trials have found some key differences to possibly explain the disparity.

  1. Lamprea-Montealegre et al summed up the findings of those secondary analyses. They focused on a few areas possibly contributing to the difference, including study design, populations, endpoints, statistics, blood pressure treatment, and more. A brief summary can be found in the table below.
Reason for Differences Conclusions
Study Design The study design for both was unique. In the case of SPRINT, a randomized, controlled, paralleled, open-label design was used. While the ACCORD-BP trial, implemented a 2 x 2 factorial design focusing on both varying glycemic control and blood pressure targets.
Population Characteristics A follow-up analysis by Mi and Mukamal, sought to determine if patient characteristics were the cause for differences in the trial outcomes. Investigators merged the data such that SPRINT-eligible patients met ACCORD criteria, vice versa. After the cohort was pooled and made similar, they found both that demographic and comorbid differences could not explain the variation between the two studies.

On the other hand, a similar study by Buckley et al aimed to determine the impact of intensive blood pressure lowering on those with type 2 diabetes. Patients enrolled came from ACCORD-BP’s standard glucose group and had SPRINT eligible CVD risk factors. They concluded that intensive regimens reduced nonfatal/fatal cardiovascular outcomes. However, one important result was that intensive regimens on cardiovascular outcomes did not differ between patients with and without diabetes. A limitation of this study comes from their exclusion of participants assigned to the intensive glycemic control group, thereby eliminating an important subgroup. Lamprea-Montealegre et al felt it was not representative of the ACCORD-BP trial.

Primary Composite Endpoints When comparing the primary endpoint, this study noted ACCORD-BP (no significant reduction in CVD death with intensive) placed more weight on cardiovascular death compared to SPRINT (reduction in CVD death noted). Additionally, the cause for CVD death was not well determined in ACCORD-BP (56%) compared to SPRINT (95%). This evidence suggests population differences possibly providing some of the differences.
Blood Pressure Interventions Both ACCORD-BP and SPRINT were similar in their selection of antihypertensive agent, number of medications used, and how they measured blood pressure. These features are simply not enough to describe the divergence. Some do question if the method of blood pressure measurement might have had an effect. SPRINT measured sans an observer while ACCORD-BP did not specifically state if patient were or were not observed.
Type 2 Diabetes Type 2 diabetes inherently predisposes people to microvascular and macrovascular complications. From increased risk of sudden cardiac arrest to polypharmacy, many reasons could explain the responsiveness of a person with type 2 diabetes to intensive blood pressure lowering regimens.

Overall, based on the variety of information presented by Lamprea-Montealegre et al, it still seems that more investigation is needed to truly explain the differences between the two studies. While this article consolidated some ideas, more questions were uncovered than before. Some of the study features described here may have some effect on the divergence identified between the ACCORD-BP and SPRINT trial or none at all. Countless studies have been performed to try to connect the dots between these two trials. But a question always seems to arise, is it appropriate to implement SPRINT trial conclusions in the population with diabetes? The authors suggest that basing patient care on the SPRINT trial for people who have diabetes should be done with caution. For now, it seems the best approach is to implement and practice the strategies provided in the most up-to-date guidelines and as always consider the specific qualities of your patient when developing a pharmacotherapeutic regimen.

Practice Pearls:

  • Lamprea-Montealegre et al looked at the divergent conclusions found in the ACCORD-BP and SPRINT trial.
  • The following study features could possibly attribute to the differences noted, including study design, populations, primary endpoints, statistical components, and methods of blood pressure measurement. It remains unclear if these features are true explanations for the disparity seen between trials.
  • Overall, at this time, patients who have diabetes should continue to be treated based on current recommendations found in the ADA and ACC/AHA guidelines.

References:

Lamprea-Montealegre, J., and de Boer, I. Reevaluating the Evidence for Blood Pressure Targets in Type 2 Diabetes. Diabetes Care. 41.6 (2018): 1132-1133. https://doi.org/10.2337/dci17-0063.

American Diabetes Association. 1. Improving Care and Promoting Health in Populations: Standards of Medical Care in Diabetes-2018. Diabetes Care. 41.Supplement 1 (2018): S86-S104. https://doi.org/10.2337/dc18-S009.

Sprint Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 373.22 (2015): 2103-2116. DOI: 10.1056/NEJMoa1511939.

ACCORD Study Group. Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus. N Engl J Med. 362 (2010): 1575-1585. DOI: 10.1056/NEJMoa1001286.

Buckley, L., Dixon, D., Wohlford, G., Wijesinghe, D., Baker, W., and Van Tassell, B. Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of the ACCORD-BP Trial. Diabetes Care. 2017. https://doi.org/10.2337/dc17-1366.

Mi, M. and Mukamal, K. Comment on Buckley et al. Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of ACCORD-BP. Diabetes Care. 41.6 (2018). E84-e85. https://doi.org/10.2337/dc17-2482.

Kaytie A. Weierstahl, Pharm.D. Candidate, LECOM School of Pharmacy