By Connor Emdin
September 6, 2017
In recent years, there has been considerable shift in treatment targets for blood pressure management. In 2014, the Eighth Joint National Commission (JNC 8) guidelines controversially up-revised blood pressure targets and recommended a target blood pressure of less than 140/80mm Hg in adults less than 60 years of age, increasing to less than 150/90mm Hg in those aged over 60 years. They argued that at the time, no randomized trial had demonstrated that lower blood pressure targets were associated with reduced risk of cardiovascular disease or death.1 These recommendations were a cause of heated debate and were inconsistent with recommendations from several other expert bodies, including American Heart Association and American College of Cardiology.
In the midst of this uncertainty, the Systolic Blood Pressure Intervention Trial (SPRINT) was reported, testing whether intensive blood pressure lowering (to a systolic blood pressure (SBP) target of 120 mm Hg) prevents major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) relative to a systolic target of 140 mm Hg.2 SPRINT enrolled over 9,500 patients at increased cardiovascular risk, but without diabetes. It showed that at three years, intensive blood pressure treatment to a target SBP <120 mm Hg significantly reduced the risk of major cardiovascular events by 25% and all-cause mortality by 27%. The authors concluded that intensive blood pressure lowering can prevent cardiovascular and death relative to usual care.2 The study has reignited debate around blood pressure targets.
…although SPRINT showed impressive effects in prevention of cardiovascular disease, it also showed relatively high rates of treatment-related adverse effects, raising questions as to how these findings should be applied in the general population.
Approximately 17 million Americans meet the eligibility criteria for SPRINT and may gain benefit from application of its findings. However, although SPRINT showed impressive effects in prevention of cardiovascular disease, it also showed relatively high rates of treatment-related adverse effects, raising questions as to how these findings should be applied in the general population. Two additional analyses were recently published in the New England Journal of Medicine, exploring the potential benefits and costs of intensive blood pressure lowering.3,4 First, does intensive blood pressure control affect quality of life?3 Second, is intensive blood pressure lowering cost-effective?4
In the first article, investigators examined whether intensive blood pressure lowering in SPRINT adversely influenced the self-reported quality of life of participants.3 The intensive treatment group in SPRINT experienced higher rates of adverse events, including hypotension and syncope, which could adversely affect patient well-being and be a particular concern for older patients.5 Investigators measured the Physical Component Summary Score of the Veterans RAND 12-Item Health Survey (VR-12), which measures self-reported physical health; the Mental Component Summary (MCS) of the VR-12, which measures self-reported mental health; and Patient Health Questionnaire 9-item depression scale (PHQ-9), which measures depressive symptoms. Investigators also measured satisfaction with blood pressure treatment and medication adherence using the Morisky Medication Adherence Scale.
No significant differences in the physical or mental components of the Veterans RAND 12-Item Health Survey were observed (Table).3 A similar decline of 0.23 points in the physical health score (p=0.9) and an increase of 0.15-0.14 points in the mental health score (p=0.79) between the intensive BP lowering arm and control arm of the trial was observed. Slightly more individuals in the intensive BP-lowering arm were satisfied with their treatment than in the control arm (74% vs 71%, p=0.03). Similar proportions of individuals were adherent to their BP-lowering medications at twelve months (p=0.21). Of particular note, the results also did not vary when stratified according to age > or <75 years, or with increasing numbers of comorbid conditions, indicating that even in older patients and those with a greater burden of comorbid disease, intensive blood pressure lowering did not adversely impact physical health, mental health, or depressive symptoms.3
Table. Patient reported outcomes in the SPRINT trial.
|Intensive BP Lowering (<120 mm Hg)||Usual Care (<140 mm Hg)||p-value|
|Mean Change in Physical Component Summary Score (Physical Health)||-0.23 points per year||-0.23 points per year||p=0.9|
|Mean Change in Mental Component Summary Score (Mental Health)||0.15 points per year||0.14 points per year||p=0.79|
|Patient Health Questionnaire 9-item Depression Scale (Depression Scale)||-0.03 points per year||-0.03 points per year||p=0.86|
|Very satisfied with blood pressure treatment at twelve months?||74%||71%||p=0.03|
|Highly adherent to blood pressure medication at twelve months?||45%||44%||p=0.21|
In a second article in the same issue of NEJM, Bress et al reported the results of a microsimulation model to estimate the cost-effectiveness of intensive blood pressure lowering therapy, per quality-adjusted life-year saved (QALY, a commonly used metric to measure the cost effectiveness of different interventions).4 In the simulation, they assessed several different outcome models, incorporating factors such as the cost of treatment-related adverse events, the effect of varied adherence to medication, and the possibility of variable long-term benefits. The majority of treatment-related costs including medications, clinic visits, and laboratory costs were incurred earlier on, whereas cost saving from decreased cardiovascular disease and death accumulated with time. The model was sensitive to whether the benefits of treatment lasted beyond the five-year period of the trial; with lower costs anticipated the longer the benefit was seen. For example, in a best-case scenario, where medication adherence and treatment benefit persisted for the lifetime of the patient, intensive control cost just $28,000 per QALY gained. In contrast, if there were a reduction in benefit after five years, the cost of intensive treatment would be $47,000 per QALY gained. However, in the majority of simulations, the cost per QALY was below the commonly used threshold of $50,000 per QALY to determine a cost-effective intervention. The authors concluded that intensive blood pressure lowering therapy prevents cardiovascular disease and does so in a cost-effective manner.4
Taken together with the primary trial, these studies indicate that targeting an SBP of <120mm Hg in patients at increased cardiovascular risk, including those of older age, is associated with reduced cardiovascular disease and mortality, does not negatively impact quality of life, and is a cost effective intervention.
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- James PA, Oparil S, Carter BL, 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 : the journal of the American Medical Association. 2014;311(5):507-520. doi:10.1001/jama.2013.284427.
- SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015;373(22):151109120153006–2116. doi:10.1056/NEJMoa1511939.
- Berlowitz DR, Foy CG, Kazis LE, et al. Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes. N Engl J Med. 2017;377(8):733-744. doi:10.1056/NEJMoa1611179.
- Bress AP, Bellows BK, King JB, et al. Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2017;377(8):745-755. doi:10.1056/NEJMsa1616035.
- Xie X, Atkins E, Lv J, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016;387(10017):435-443. doi:10.1016/S0140-6736(15)00805-3.
Connor Emdin is a post-doctoral research fellow in Sek Kathiresan’s lab at the Broad, specializing in the genetics of cardiovascular disease. He completed his doctorate in cardiovascular epidemiology at the University of Oxford from 2009-2013.