Mitigating potential bias: Only published trial data is presented. Recommendations are consistent with current practice patterns. References are made to published guidelines (i.e. CHEP, JNC8, ESC – see references)
What I did before
Hypertension affects over 1 in 5 Canadians and is one of the leading causes of cardiovascular disease, including coronary artery disease and heart failure.1,2 Uncontrolled hypertension is a risk factor for stroke (both ischemic and hemorrhagic), retinopathy, chronic kidney disease (CKD), and peripheral vascular disease. Epidemiologic studies show that the risk of cardiovascular disease increases above a blood pressure of 115/75 mmHg.3
The 2015 CHEP guidelines recommended a blood pressure treatment target of 140/90 mmHg or less in most individuals with hypertension (Table 1).4-6 Elderly populations, particularly patients 80 years and older, may benefit from a more conservative target of 150/80 mmHg, according to the HYVET study.7 Patients with diabetes may benefit from a lower blood pressure target of 130/80 mmHg, although this recommendation remains controversial.4 In the ACCORD study, intensive blood pressure targets (systolic less than 120 mmHg) in diabetic patients did not demonstrate any significant benefit over standard targets (systolic less than 140 mmHg).8
What changed my practice
The SPRINT trial was recently published in the New England Journal of Medicine and compares intensive versus standard blood pressure control in patients with increased cardiovascular risk.9 In SPRINT, 9361 patients with a systolic blood pressure between 130 to 180 mmHg were randomized to an intensive treatment target (systolic less than 120 mmHg) or standard target (systolic less than 140 mmHg).9 Patients were selected to have an increased cardiovascular risk, defined as one or more of the following: clinical or subclinical cardiovascular disease other than stroke, previous CKD (eGFR 20-60 mL/min/1.73 m2), 10-year Framingham risk of 15% or greater, or greater than 75 years of age.9 Patients with diabetes or prior stroke were excluded from the study. Adverse events, including acute kidney injury, were identified from the hospital discharge summary, adjudicated by a safety officer, and reviewed by a safety committee.
After a median follow-up of 3.26 years, the mean systolic blood pressures were 121.5 mmHg and 134.6 mmHg in the intensive and standard treatment groups, respectively.9 Patients in the intensive group were taking one additional anti-hypertensive medication (2.8 vs. 1.8), with the relative distribution of agents similar (no restriction in type of medications used).9 The trial was terminated early due to a significant reduction in the composite primary outcome of myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, and death from cardiovascular causes in the intensive treatment group (5.2% vs. 6.8%, HR 0.75, p<0.001).9 These findings were present in all subgroups, irrespective of age, sex, ethnicity, baseline systolic blood pressure, previous cardiovascular disease, or previous CKD. The authors also reported a reduction in secondary outcomes, including death from any cause (3.3% vs. 4.5%, HR 0.73, p=0.003), death from cardiovascular causes (0.8% vs. 1.4%, HR 0.57, p=0.005), and heart failure (1.3% vs. 2.1%, HR 0.62, p=0.002).9
There was no difference in the overall serious adverse events between the two groups (38.3% vs. 37.1%, HR 1.04, p=0.25). However, hypotension (2.4% vs. 1.4%, HR 1.67, p=0.001), syncope (2.3% vs. 1.7%, HR 1.33, p=0.05), electrolyte abnormality (3.1% vs. 2.3%, HR 1.35, p=0.02), and acute kidney injury (4.1% vs. 2.5%, HR 1.66, p<0.001) were more common in the intensive treatment group.9 There was no difference in injurious falls (2.2% vs. 2.3%, HR 0.95, p=0.71).9
What I do now
The SPRINT trial brings into question the optimal blood pressure target in the hypertensive patient and reflects a departure from the targets currently recommended in North American and European guidelines (Table 1).4-6 The authors reported an absolute risk reduction of 1.6% in their primary outcome with intensive treatment, translating to a number needed-to-treat of 61 to prevent one primary outcome, and 90 to prevent one death (from any cause).9 These findings were present in all subgroups, with potentially a stronger signal in those 75 years and older, with a baseline systolic blood pressure ≤132 mmHg, and without previous CKD. Notably, there was no reduction in stroke as a single endpoint (1.3% vs. 1.5%, HR 0.89, p=0.50).9
Despite the potential benefits of intensive blood pressure control, there remain significant risks. We calculated a number needed-to-harm of 106 for hypotension, 172 for syncope, and 61 for acute kidney injury. Thus, patients with a history of hypotension and syncope should be closely followed, and electrolytes and renal function monitored routinely, after the initiation of additional anti-hypertensives medications. We also do not know whether the positive findings in SPRINT represent the benefit from a single class of anti-hypertensives (i.e. ACE inhibitors), as patients in the intensive treatment group used more medications from all drug classes.9
The results of SPRINT also are at odds with previous studies. In patients with diabetes (i.e. ACCORD), there was no difference in the primary outcome between intensive versus standard therapy, but more serious adverse events with intensive therapy.8 However, the ACCORD study may have suffered from insufficient power and poor study design – a combined analysis of the SPRINT and ACCORD data demonstrated a significant reduction in event rate with intensive blood pressure control.10 Furthermore, studies of hypertension management in the elderly have targeted a blood pressure of 150/80 mmHg or less (i.e. HYVET).7 The SPRINT trial sends a strong message that intensive therapy in these individuals may still offer additional benefit, although one must consider the risk of adverse events in this population.
The SPRINT trial brings into question the optimal blood pressure target for the non-diabetic hypertensive patient with increased cardiovascular risk. In SPRINT, the authors demonstrated a significant reduction in their composite primary outcome and death from any cause with an intensive treatment target. Previous, smaller studies in diabetic and elderly patients have not demonstrated such significant reductions in cardiovascular and mortality endpoints.
The results of the SPRINT trial have now been incorporated in the 2016 CHEP guidelines (Table 1).11 Similar to the guidelines, we would consider treating individuals at increased cardiovascular risk to an intensive treatment target, although this decision must be balanced with the increased risk for adverse events, including hypotension, syncope, and acute kidney injury. The practitioner must balance the number needed-to-treat, number needed-to-harm, and patient preferences to determine the optimal blood pressure target and choice of therapy for each individual.
Table 1. 2015 and 2016 CHEP Guidelines4,11
|Adults with Hypertension||≤ 140/90 mmHg|
|Elderly (age ≥ 80 years)||≤ 150/90 mmHg|
|Diabetes mellitus||≤ 130/80 mmHg|
|New Recommendation in 2016 CHEP Guidelines: Selected high-risk patients†||SBP ≤ 120 mmHg|
†Selected high-risk patients who may potentially benefit from lower BP targets, referring to patients enrolled in the SPRINT trial.9,11
References and Additional Reading
- Robitaille C, Dai S, Waters C, et al. Diagnosed hypertension in Canada: incidence, prevalence and associated mortality. CMAJ. 2012 Jan 10;184(1):E49-56. (View)
- Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. (View with CPSBC or UBC) DOI: 1016/S0140-6736(04)17018-9
- Lewington S, Clarke R, Qizilbash N, 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 Dec 14;360(9349):1903-13. (View with CPSBC or UBC) DOI: 10.1016/S0140-6736(02)11911-8
- Daskalopoulou SS, Rabi DM, Zarnke KB, et al. The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2015 May;31(5):549-68. (View with CPSBC or UBC) DOI: 10.1016/j.cjca.2015.02.016
- 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. 2014 Feb 5;311(5):507-20. (Request with CPSBC or view UBC) DOI: 10.1001/jama.2013.284427
- Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013 Jul;34(28):2159-219.(View)
- Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008 May 1;358(18):1887-98. (View)
- ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. (View)
- SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16. (View)
- Perkovic V, Rodgers A. Redefining Blood-Pressure Targets–SPRINT Starts the Marathon. N Engl J Med. 2015 Nov 26;373(22):2175-8. (View)
- Leung AA, Nerenberg K, Daskalopoulou SS, et al. Hypertension Canada’s 2016 CHEP Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention and Treatment of Hypertension. Can J Cardiol. 2016. (View with CPSBC or UBC) DOI: 10.1186/s12916-015-0502-5