9 responses to “Comparing intensive versus standard blood-pressure control: The SPRINT Trial”

  1. I haven’t been in practice too many years but have already had the experience of determining my practice based on a single (not very well designed) RCT and later seeing the evidence pile up to suggest I was too quick to jump on a bandwagon. I worry about this with a trail like SPRINT.

    The Therapeutics Initiaitve at UBC did a good review of this trial and the practical implications here: http://www.ti.ubc.ca/2016/04/07/98-sprint-change-approach-blood-pressure-targets/

    I think their review is a bit more balanced, although I appreciate the acknowledgement of harms in this review.

    When there are multiple well-designed RCTs all showing similar effects, I’ll be open to changing my practice on this.

  2. Exactly what Joel said.
    He beat me to it!
    When the SPRINT trial is considered in addition to all existing trials, it doesn’t move the marker for treatment thresholds. Furthermore, there is no convincing evidence that diabetics require more strict control. The TI has some excellent slides covering this specific question as well.

    In the spirit of transparency and to allow readers to apply critical thinking, it is important for author’s disclosures to be listed on this site. Unfortunately I believe there have been some (all) omitted for the second author. Hopefully the process of disclosure can be more comprehensive in future.

  3. The SPRINT study was sponsored by Takeda and Arbor Pharmaceuticals, both of which produce anti-hypertensive drugs. Should physicians be suddenly changing their practice based on one industry-sponsored study?

  4. I generally do not change my practice based on a single trial either. I put more emphasis on lifestyle change than on medication to begin with and this was not mentioned in the article at all.

  5. Regarding D. Moore’s comment. The trial was government funded and not sponsored by Takeda ( which was taken over by Arbor. Takeda contributed two study medications (azilsartan alone and azilsartan combined with chlorthalidone), which were two in a formulary of many antihypertensive medications. Azilsartan is an angiotensin II receptor antagonist. Chlorthalidone is a commonly prescribed diuretic. Approximately 5% of participants were on one of these donated drugs. Various classes of standard antihypertensive medications were included in the formulary for the SPRINT trial, including diuretics, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, and beta blockers, among others. At this time, most SPRINT blood pressure medications are generic.

    An important note about this significant trial is the that blood pressure measure were take after 5 minutes rest by an automated 3 reading ( 2 minutes apart) Omron model 907 device. This method give lower readings that the the single physician reading reading that most physicians use. I recently switched to an Omron and measure BP in a separate room. I get significantly lower readings this way. This method is recommended in the 2016 CHEP guidelines.
    TI thinks there is performance bias as they got such good control with 3 drugs in many patients. I have being able to achieve these numbers in my office after switching to an 3 reading automated device. ( I cycle patients through twice getting 6 readings)

  6. Thanks for the clarification Dr Barrs. It’s all in the detail.

  7. Thank you to all those that have read our article and those who have sent us their comments. We would like to take this opportunity to respond to the submitted comments.

    First, there were several concerns regarding the generalizability of the SPRINT trial. The findings in SPRINT do not apply to patients with diabetes, history of stroke, significant proteinuria, one-minute standing SBP less than 110 mmHg, in addition to other exclusion criteria (see SPRINT appendix).(1) The SPRINT results only apply to patients 50 years and older with an SBP between 130-180 mmHg and a predefined risk factor, such as chronic kidney disease, cardiovascular disease, elevated Framingham risk, or age greater than 75 years. While it is the authors’ opinion that the SPRINT trial changes our practice, the Canadian Hypertension Education Program (CHEP) represents a well-respected national authority in the diagnosis, assessment, prevention, and treatment of hypertension. The 2016 CHEP Guidelines have reinforced the importance of applying intensive blood pressure control only in selected high-risk patients.(2)

    Epidemiological studies show an increasing risk of cardiovascular events above a blood pressure of 115/75mmHg.(3) Almost half of the blood pressure-related disease burden occurs in people with a SBP less than 140mmHg. The Cochrane systematic review cited by the Therapeutics Initiative was published in 2009, with an updated review unpublished at this time.(4) Recently, there were two meta-analyses published in the Lancet in November 2015 reviewing the effect of intensive blood pressure lowering.(5,6) Xie et al. reviewed 19 trials including 44,989 patients but did not include SPRINT due to publication timing.(5) Despite this, the authors calculated a 14% reduction in major cardiovascular events with intensive blood pressure lowering (RR 0.87), with benefits extending to those with a blood pressure less than 140 mmHg.(5) There was also a reduction in microvascular events including albuminuria and retinopathy progression. This meta-analysis demonstrated an increase in severe hypotensive effects with more intensive BP lowering, but there was no suggestion that these adverse effects would outweigh the benefits of treatment. Over half of the trials included in the Xie et al. systematic review were published after 2009 and were not included in the original Cochrane analysis.

    The second meta-analysis (Ettehad et al.) reviewed 123 studies (including SPRINT) with 613,815 patients.(6) The authors included all trials comparing blood pressure treatment versus placebo, trials comparing different blood pressure targets (i.e. SPRINT), and trials comparing different classes of blood pressure medications. The authors demonstrated a 20% reduction in major cardiovascular events (RR 0.80) for every 10 mmHg blood pressure reduction, with benefits extending to blood pressures less than 130 mmHg.(6) There was also a reduction in all-cause mortality (RR 0.87) for every 10 mmHg reduction, and all findings were demonstrated independent of baseline cardiovascular disease.

    Interestingly, the systolic blood pressure target of less than 140 mmHg that is most often followed is based on only Grade C evidence (2015 CHEP Guidelines), compared to the current intensive treatment recommendation (2016 CHEP Guidelines), which reflects Grade B evidence.(2)

    It is important to evaluate the potential funding biases that can influence a study. As stated by Dr. Barss, the SPRINT trial was funded by the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes on Aging, and the National Institute of Neurological Disorders and Stroke. The provision of study medications and method of blood pressure measurement has been clearly explained in Dr. Barss’ response. In British Columbia, the provincial drug formulary has just announced price reductions for most commonly prescribed anti-hypertensive medications, making these medications affordable for most patients. The method of anti-hypertensive monitoring, as noted by Dr. Barss, is also an important point.

    Finally, we agree that lifestyle remains an important pillar of anti-hypertensive treatment. Space limitations in our original article precluded the discussion of lifestyle and non-pharmacologic therapies. Previous studies, such as the DASH (Dietary Approaches to Stop Hypertension) trial, have demonstrated marked reductions (up to 12 mmHg) with dietary changes in hypertensive patients.(7) Exercise has been demonstrated to reduce blood pressure (4-5 mmHg) in pre-hypertensive and hypertensive adults, with higher intensity exercise showing greater benefit.(8) Likewise, excess alcohol consumption has a marked effect on blood pressure and the risk of hypertension, in addition to other cardiovascular and systemic risks.(9)

    Thank you for your questions and comments. We hope that our responses have sufficiently addressed your concerns.
    Drs. Christopher Cheung and Kenneth Gin

    (1) 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.
    (2) 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 May;32(5):569-88.
    (3) 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.
    (4) Arguedas JA, Perez MI, Wright JM. Treatment blood pressure targets for hypertension. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD004349.
    (5) 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 Jan 30;387(10017):435-43.
    (6) Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016 Mar 5;387(10022):957-67.
    (7) Sacks FM, Appel LJ, Moore TJ, et al. A dietary approach to prevent hypertension: a review of the Dietary Approaches to Stop Hypertension (DASH) Study. Clin Cardiol. 1999 Jul;22(7 Suppl):III6-10.
    (8) Williamson W, Foster C, Reid H, et al. Will Exercise Advice Be Sufficient for Treatment of Young Adults With Prehypertension and Hypertension? A Systematic Review and Meta-Analysis. Hypertension. 2016 Jul;68(1):78-87.
    (9) Chen L, Smith GD, Harbord RM, et al. Alcohol intake and blood pressure: a systematic review implementing a Mendelian randomization approach. PLoS Med. 2008 Mar 4;5(3):e52.

  8. i will change my practice

  9. An interesting summary of the discussion regarding SPRINT at the European Society of Cardiology meeting in Rome posted yesterday on the MedPage Today website: http://www.medpagetoday.com/meetingcoverage/esc/59908 discussing the controversy surrounding the method of BP monitoring used in the trial.

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