By Martin Lipsky, MD
Chancellor, South Jordan Campus, Roseman University of Health Sciences, South Jordan, UT
Dr. Lipsky reports no financial relationships relevant to this field of study.
SYNOPSIS: The SPRINT study, which explored the effect of targeting blood pressure treatment to a goal of < 120 mmHg, ended early because of significantly lower rates of fatal and nonfatal cardiovascular events and death from any cause. However, the incidence of acute kidney damage hypotension, syncope, and electrolyte abnormalities were higher in the treatment group. A recent meta-analysis also supports the benefit of targeting lower blood pressure levels.
SOURCES: The SPRINT research group: A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103-2116.
Xie X, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: Updated systematic review and meta-analysis. Lancet 2015 Nov. pii: S0140-6736(15)00805-3. doi: 10.1016/S0140-6736(15)00805-3. [Epub ahead of print].
The Oct. 29, 2015, issue of Internal Medicine Alert discussed the Systolic Blood Pressure Intervention Trial (SPRINT), which ended early because of a significantly lower rate of cardiovascular events in the intensive-treatment group than in the standard-treatment group.1 All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% confidence interval [CI], 0.60-0.90; P = 0.003). However, at that time the full study was not yet published. Concerns about the risk of adverse events from aggressive treatment suggested a need for caution before translating the SPRINT findings into clinical practice. Indeed, an article in The New England Journal of Medicine about SPRINT reported that the rates of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.2 However, despite the risk of acute renal injury, the authors noted there was no evidence of substantial permanent kidney damage associated with the lower systolic treatment group, although the possibility of long-term damage could not be excluded.
In another study to help guide hypertension treatment, Xie et al conducted a meta-analysis examining the benefit and safety of intensive blood pressure-lowering strategies.3 The study systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and 2015. The analysis identified 19 randomized, controlled trials representing 44,989 participants. The average blood pressure in the more intensive blood pressure-lowering treatment groups was 133/76 mmHg, compared with 140/81 mmHg in the less intensive treatment groups. Patients in the more intensive treatment groups experienced a risk reduction for major cardiovascular events (14%; 95% CI, 4-222), myocardial infarction (13%; CI, 0-24), stroke (22%; CI, 10-32), albuminuria (10%; CI, 3-16), and retinopathy progression. However, there were no clear benefits on heart failure, cardiovascular death, total mortality, or end-stage kidney disease among the aggressive treatment study arms. The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit, even in patients with systolic blood pressure < 140 mmHg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported in six of the trials and had an event rate of 1.2% per year in intensive blood pressure-lowering group participants, compared with 0.9% in the less intensive treatment group (relative risk [RR], 1.35; 95% CI, 0.93-1.97). Severe hypotension was more frequent in the more intensive treatment regimen (RR, 2.68; 95% CI, 1.21-5.89; P = 0.015), but the absolute excess was small.
COMMENTARY
Hypertension is one of the most common chronic conditions primary care providers treat. While there is clear evidence that treating high blood pressure improves outcomes, the optimal treatment target remains uncertain. The JNC 8 guidelines4 cited the ACCORD study,5 which failed to demonstrate added benefit from more intensive hypertensive treatment for individuals with type 2 diabetes, as evidence against more aggressive treatment in high-risk patients.
In contrast, investigators ended the SPRINT early because of the benefits observed in the aggressive treatment group. Since epidemiologic studies indicate that the risk of cardiovascular events increases, beginning at blood pressures > 115/75 mmHg,6 the SPRINT results intuitively make sense. However, many clinicians who struggle with managing the side effects from aggressive treatment expressed concern about the risk of adverse effects associated with aggressive treatment, even before The New England Journal of Medicine published the trial data. To no great surprise, the published paper found an increased risk of adverse effects among aggressively treated patients.
For those who favor lower treatment targets, the Xie et al meta-analysis provides additional evidence to support more intensive blood pressure lowering, including high-risk patients whose systolic blood pressure is < 140 mmHg. In combination with SPRINT findings, these results may lead to changes in hypertension treatment guidelines. The SPRINT writing group recognized that its findings differ from the ACCORD trial and noted that the difference between the trials could be due to study design, treatment interactions, or chance.2 In an editorial accompanying the Xie meta-analysis, Brunströma and Carlberg expressed that some uncertainty remains about whether diabetics or very elderly patients will benefit from lower treatment targets (< 140/90 mmHg).7
Moving forward, defining optimal blood pressure treatment targets will likely not be easy. Until new guidelines become available, it seems that if physicians can achieve lower blood pressures without causing significant side effects, the evidence supports this approach. Since side effects can be significant, physicians should not lose sight of the importance of including non-pharmacological approaches, such as weight loss and dietary sodium restrictions, when prescribing treatment. While these approaches alone are insufficient for most patients, they may be the difference between achieving lower blood pressure targets with fewer medications, lower doses, and fewer side effects. In the meantime, stay tuned for the next set of guidelines.
REFERENCES
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Lipsky M. SPRINT: The Systolic Blood Pressure Trial or ‘how low do you go?’ Internal Medicine Alert 2015;37:153-155.
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The SPRINT research group: A randomized trial of intensive versus standard blood- pressure control. N Engl J Med 2015;373:2103-2116.
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Xie X, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: Updated systematic review and meta-analysis. Lancet 2015 Nov. pii: S0140-6736(15)00805-3. doi: 10.1016/S0140-6736(15)00805-3. [Epub ahead of print].
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PA James, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-520.
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ACCORD Study Group: Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-1585.
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Lewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-1913.
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Brunströma B, Carlberg B. Lower blood pressure targets: To whom do they apply? Lancet 2015; Nov. doi:10.1016/S0140-6736(15)00816-8.
