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New data suggest overly intensive blood pressure treatment in diabetics could lead to worse CV outcomes. How should you set goals for your patients?
A new study has confirmed the benefits in diabetics of treating systolic blood pressure over 140 mmHg, in terms of lower mortality and cardiovascular (CV) morbidity. However, results also showed that treating systolic blood pressure below 140 mmHg may have no additional benefits, and may even be harmful. The study was published online in The BMJ.1
“This systematic review and meta-analyses confirms that blood pressure lowering treatment is associated with reduced mortality and cardiovascular morbidity in people with diabetes mellitus, if systolic blood pressure (SBP) before treatment is more than 140 mm Hg. If SBP is less than 140 mm Hg, however, we found no benefit… [and] an increased risk of cardiovascular death,” wrote authors Mattias BrunstrÃ¶m, PhD student and Bo Carlberg, associate professor at UmeÃ¥ University, UmeÃ¥, Sweden.
Guidelines for many years have recommended treating blood pressure to a target of 130/80 mmHg, though systematic reviews have begun to question this practice. In 2013, the American Heart Association, American Diabetes Association, American Society of Hypertension and the Eighth Joint National Committee updated their hypertension guidelines, with a general trend toward relaxation of treatment goals in diabetics to 140/90 mmHg. Some guidelines, like those of the American Diabetes Association, continue to recommend lower goals in certain subgroups of patients.2
In the study, researchers searched CENTRAL, Medline, Embase, and BIOSIS for randomized controlled trials (RCTs) that included 100 or more participants with diabetes who were treated with antihypertensives for 12 months or more. To be included, RCTs had to evaluate the active drug vs placebo, two antihypertensives vs one, or varying blood pressure targets.
The analysis included 49 trials covering 73,738 participants, the majority (number) of whom had type 2 diabetes and were already receiving antihypertensive treatment. Unpublished data from twelve trials were also included in the analysis.
In the following baseline systolic blood pressure (SBP) categories, antihypertensive use was linked to:
• >150 mmHg:
♦ 11% lower all-cause mortality risk (relative risk 0.89, 95% CI 0.80 to 0.99)
♦ 25% lower cardiovascular mortality risk (0.75, 0.57 to 0.99),
♦ 26% lower myocardial infarction risk (0.74, 0.63 to 0.87)
♦ 17% lower stroke risk (0.77, 0.65 to 0.91)
♦ 18% lower end-stage renal disease risk (0.82, 0.71 to 0.94)
• 140-150 mm Hg:
♦ 13% lower all-cause mortality risk (0.87, 0.78 to 0.98)
♦ 16% lower myocardial infarction risk (0.84, 0.76 to 0.93)
♦ 20% lower heart failure risk (0.80, 0.66 to 0.97)
• <140 mm Hg:
♦ 15% increased cardiovascular mortality risk (1.15, 1.00 to 1.32)
♦ Slightly increased all-cause mortality risk (1.05, 0.95 to 1.16)
• Treatment effects significantly worsened with each 10 mmHg decrease in baseline SBP for:
♦ Cardiovascular mortality (P=0.015), which crossed from benefit to harm at 141 mmHg
♦ Myocardial infarction (P=0.011), which crossed from benefit to harm at 132 mmHg
The results generally agree with a metanalysis published in JAMA in 2015,3 confirming the existence of a J-shaped curve regarding CVD and blood pressure with worse CVD outcomes at the lower and upper bounds of blood pressure. However, the 2015 metanalysis also found a decreased stroke risk with treating SBP less than 140 mmHg, which this new metanalysis does not confirm.
The authors suggest that overly intensive treatment could decrease blood flow to end organs, causing ischemia and leading to worse CV outcomes. Alternatively, low blood pressure could decrease coronary collateral circulation.
“[O]ur results… suggest that blood pressure treatment goals should be less aggressive in people with diabetes than without diabetes,” they concluded. “This review strongly supports blood pressure treatment in people with diabetes mellitus if SBP is more than 140 mm Hg. If SBP is already less than 140 mm Hg, however, adding additional agents might be harmful.”
• Systematic review and metanalysis found decreased mortality and cardiovascular morbidity in diabetics with before-treatment SBP over 140 mm Hg.
• With baseline SBP less than 140 mm Hg, results showed no benefit and possible harm with increased risk of CV death.
• The results confirm the existence of a J-shaped curve, suggesting worse CVD outcomes at the lower and upper bounds of blood pressure in diabetics.
1. BrunstrÃ¶m M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016 Feb 24;352:i717.
2. American Diabetes Association. Standards of medical care in diabetes-2015: summary of revisions. Diabetes Care 2015;38:S4.
3. Emdin CA, et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015;313:603-615.