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In reply: Blood pressure targets (March 2016)

George Thomas, MD, FACP, FASN, Joseph V. Nally, MD and Marc A. Pohl, MD
Cleveland Clinic Journal of Medicine July 2016, 83 (7) 488-489; DOI: https://doi.org/10.3949/ccjm.83c.07003
George Thomas
Cleveland Clinic
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Joseph V. Nally
Cleveland Clinic
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Marc A. Pohl
Cleveland Clinic
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in reply: We thank the readers for their important and insightful comments and questions.

Dr. Yilmaz raises the point that there was no mandate in the SPRINT trial to preferentially use any specific class of anti-hypertensive medications in either group. However, there was greater use of all drug classes (including diuretics and renin-angio-tensin-aldosterone blockers) in the intensive-treatment group.1 (This information was included as a supplementary appendix in the main paper, and as Table 1 in our review.) Could this have contributed to the primary cardiovascular outcome benefit seen in the intensive-therapy group, largely driven by a decreased incidence of heart failure, or could it even have masked the symptoms of heart failure rather than preventing it2,3? While this is plausible, since the SPRINT trial was designed as a “treat to target” study and not as an antihypertensive medication efficacy study, it is difficult to conclusively answer the question of potential pleiotropic effects of antihypertensive medications influencing the trial results. The authors did not comment on this in the main paper, and we agree that further analysis would be helpful in exploring this important question.

Dr. Edwards raises the question whether antihypertensive therapy confers additional cardiovascular benefit over aggressive use of statins. Statin use in the SPRINT cohort (both intensive and standard groups) was low at baseline, despite this being a population at high cardiovascular risk.1 It is unclear whether treatment practices pertaining to lipid management could have changed during the course of the trial in participants within the SPRINT cohort, particularly after the new lipid guidelines were published. The recently published HOPE-3 trial indicated cardiovascular benefit with statins used as a primary prevention strategy in older persons with intermediate cardiovascular risk.4,5 Notably, outcomes with combination therapy in this trial using a statin plus anti-hypertensive therapy were not significantly better than with statin alone, except in the subgroup of participants who were in the upper third of systolic blood pressure levels, where combination appeared to benefit more. This study, of course, was done in a population with lower cardiovascular risk than in SPRINT, and the antihypertensive medications used (candesartan and hydro-chlorothiazide) were not at maximal doses. There is also a question of whether use of chlorthalidone in HOPE-3 may have been more effective.

We agree with Dr. Edwards that this is an important question that merits further exploration, especially in the broader context of treatment based on cardiovascular risk.

  • Copyright © 2016 The Cleveland Clinic Foundation. All Rights Reserved.

REFERENCES

    1. SPRINT Research Group
    2. Wright JT Jr.,
    3. Williamson JD,
    4. Whelton PK,
    5. et al
    . A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373:2103–2116.
    1. Mancia G
    . The SPRINT trial: cons. J Am Coll Cardiol 2015 Dec 2. www.acc.org/latest-in-cardiology/articles/2015/12/01/10/04/the-sprint-trial-cons. Accessed May 18, 2016.
    1. Zanchetti A,
    2. Liu L,
    3. Mancia G,
    4. et al
    . Continuation of the ESH-CHL-SHOT trial after publication of the SPRINT: rationale for further study on blood pressure targets of antihypertensive treatment after stroke. J Hypertens 2016; 34:393–396.
    1. Yusuf S,
    2. Lonn E,
    3. Pais P,
    4. et al
    5. HOPE-3 Investigators
    . Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med 2016 Apr 2 [Epub ahead of print]. www.nejm.org/doi/full/10.1056/NEJMoa1600177. Accessed May 19, 2016.
    1. Cushman WC,
    2. Goff DC Jr.
    . More HOPE for prevention with statins. N Engl J Med 2016 Apr 2 [Epub ahead of print]. www.nejm.org/doi/full/10.1056/NEJMe1603504. Accessed May 19, 2016.

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