PROBLEMS OF EVALUATING BLOOD PRESSURE MEASUREMENT IN MODERN CLINICAL TRIALS (THE CASE OF SPRINT STUDY RESULTS)

The article presents a critical analysis of the results of a large clinical trial SPRINT. The focus is on the issues related to the blood pressure (BP) measurement in this trial.

The aim of SPRINT trial was to prove the benefit of reducing systolic BP (SBP) below 120 mm Hg in high-risk hypertensive patients. A total, 9,631 highrisk participants without history of diabetes mellitus or stroke were randomly allocated to a standard treatment group (target SBP<140 mm Hg) or an intensive treatment group (target SBP<120 mm Hg). Significantly lower rates of all-cause mortality (by 27%) and cardiovascular events (by 25%) were observed in the intensive treatment group, compared to the standard treatment one. Therefore, the intervention was stopped early, after a mean follow-up of 3.3 years (instead of 5 years, as specified in the study protocol).

However, the SPRINT study used an unusual method of clinical BP measurement, the so-called automatic office BP (AOBP) measurement. An important feature of AOBP is that it provides significantly lower BP values, compared to the conventional clinic BP measurement. This article reviews the publications which aimed to provide an independent evaluation of the SPRINT results. It appears that if traditional clinic BP measurement was used in SPRINT, the mean SBP level in the control group could be approximately 150 mm Hg, which is substantially higher than the generally accepted threshold of 140 mm Hg. This could explain a higher prevalence of cardiovascular events in the control group. The estimated SBP level in the intensive treatment group (132-136 mm Hg) is not very different from the standard threshold.

Therefore, the SBP target in the treatment of hypertension remains unchanged at <140 mm Hg. AOBP is a specific subtype of the clinic BP measurement. The currently proposed AOBP threshold (135/85 mm Hg) warrants further investigation.

1. Asmar R., Zanchetti A. Guidelines for the use of self blood pressure monitoring: a summary report of the first international consensus conference. J Hypertens. 2000;18:493-508.

2. O’Brien E., Asmar R., Beilin L. et al. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens. 2005;23(4):697-701. doi: 10.1097/01.hjh.0000163132.84890.

3. Recommendations for Blood Pressure Measurements in Humans and Experimental Animals. Part I: Blood Pressure Measurement in Humans. A statement for professionals from the subcommittee of professional and public education of the American heart association council on high blood pressure research. Circulation. 2005;111:697-716. doi: 10.1161/01.ATV.0000158419.98675.d7.

4. European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring. J Hypertens. 2008 Aug;26(8):1505-26. doi: 10.1097/HJH.0b013e328308da66.

5. Parati G., Stergiou G. S., Asmar R., et al. on behalf of ESH Working Group on Blood Pressure Monitoring. European Society of Hypertension Practice Guidelines for home blood pressure monitoring. J Hum Hypertens. 2010 Dec;24(12):779-85. doi: 10.1038/jhh.2010.54.

6. O’Brien E., Parati G., Stergiou G. et al. on behalf of the European Society of Hypertension Working Group on Blood Pressure Monitoring Ambulatory blood. European Society of Hypertension Position Paper on Ambulatory Blood Pressure Monitoring. J Hypertens. 2013;31:1731-68. doi: 10.1097/HJH.0b013e328363e964.

7. Parati G., Stergiouc G., O’Brien E., Asmare R. et al. on behalf of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014; 32:1359-66. doi: 10.1097/HJH.0000000000000221.

8. Stergiou G.S., Parati G., Vlachopoulos C., et al. Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: current status and future directions. Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability. J Hypertens. 2016; 34:1665-177. doi: 10.1097/HJH. 0000000000000969.

9. Redon J., Lurbe E. Ambulatory blood pressure monitoring is ready to replace clinic blood pressure in the diagnosis of hypertension: con side of the argument. Hypertension. 2014;64:1169-74. doi: 10.1161/HYPERTENSIONAHA.114.03883.

10. Niiranen T.J., Asayama K., Thijs L., et al. International Database of Home blood pressure in relation to Cardiovascular Outcome (IDHOCO) Investigators. Outcome-driven thresholds for home BPM: international database of home blood pressure in relation to cardiovascular outcome. Hypertension. 2013;61:27-34. doi: 10.1161/HYPERTENSIONAHA.111.00100.

11. Kjeldsen S.E., Lund-Johansen P., Nilsson P.N., Mancia G. Unattended Blood Pressure Measurements in the Systolic Blood Pressure Intervention Trial Implications for Entry and Achieved Blood Pressure Values Compared With Other Trials. Hypertension. 2016;67:808-12. doi: 10.1161/HYPERTENSIONAHA.116.07257.

12. Lewington S., Clarke R., Qizilbash N., et al. Prospective Studies Collaboration. 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;360:1903-13. doi: 10.1016/S0140-6736(02)11911-8.

13. Hansson L., Zanchetti A., Carruthers S.G., et al. Effects of intensive blood pressure lowering and lowdose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. HOT Study Group. Lancet. 1998;351:1755-62. doi: 10.1016/S01406736(98)04311-6.

14. Cushman W.C., Evans G.W., Byington R.P. et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-85. doi: 10.1056/NEJMoa1001286.

15. Odden M.C., McClure L.A., Sawaya B.P., et al. Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Sub-cortical Strokes trial. Hypertension. 2016;67:63-9. doi: 10.1161/HYPERTENSIONAHA.115.06480.

16. Thomopoulos C., Parati G., Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels updated overview and meta-analyses of randomized trials. J Hypertens. 2016;34:613-22. doi: 10.1097/HJH.0000000000000881.

17. Thomopoulos C., Parati G., Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. Effects at different baseline and achieved blood pressure levels-overview and metaanalyses of randomized trials. J Hypertens. 2014;32:2296-304. doi: 10.1097/HJH. 0000000000000379.

18. Wright J.T., Williamson J.D., Whelton P.K. et al. A randomized trial of intensive versus standard blood pressure control. N Engl J Med. 2015;373:2103-16. doi: 10.1056/NEJMoa1511939.

19. Kolata G. Study testing blood pressure says go lower. New York Times. September 12; 2015.

20. Bernstein L. Federal researches urge older adults to aim for much lower blood pressure. Washington Post. September 12; 2015.

21. Drazen J.M., Morrissey S., Campion E.W., Jarcho J.A. A SPRINT to the Finish. N Engl J Med. 2015;373:2174-5. doi: 10.1056/NEJMe1513991.

22. Taylor A.A., Mancia G. The SPRINT Trial Pros and Cons. American College of Cardiology 02.12.2015; (Parts I II). Available at: http://www.acc.org/latest-in-cardiology/articles/2015/12/01/10/04/the-sprint-trial-pros. Checked by Jan 31, 2018.

23. Zanchetti A., Liu L., Mancia G. et al. ESH-CHL-SHOT trial investigators. Continuation of the ESH-CHLSHOT 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. doi: 10.1097/ HJH.0000000000000853.

24. Schiffrin E.L., Calhoun D.A., Flack J.M. SPRINT proves that lower is better for nondiabetic high-risk patients, but at a price. Am J Hypertens. 2016;29:2-4. doi: 10.1093/ajh/hpv190.

25. Kjeldsen S.E., Lund-Johansen P., Nilsson P.M., Mancia G. Unattended blood pressure measurements in the Systolic Blood Pressure Intervention trial: implications for entry and achieved blood pressure values compared with other trials. Hypertension. 2016;67:808-12. doi: 10.1161/HYPERTENSIONAHA.116.07257.

26. Parati G., Ochoa J.E., Bilo G., Zanchetti A. SPRINT Blood Pressure Sprinting Back to Smirk's Basal Blood Pressure? Hypertension. 2017;69:15-9. doi: 10.1161/HYPERTENSIONAHA.116.08216.

27. Smirk F.H. Casual and basal blood pressures IV. Their relationship to the supplemental pressure with a note on statistical implications. Br Heart J. 1944;6:176-82.

28. Daskalopoulou S.S., Rabi D.M., Zarnke K.B., Dasgupta K. et al. The 2015 Canadian Hypertension Education Program Recommendations for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Canadian Journal of Cardiology. 2015;31(5):549-68. doi: 10.1016/j.cjca.2015.02.016.

29. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-85. doi: 10.1056/NEJMoa1001286.

30. The SPS3 Study Group. Effects of blood pressure targets in patients with recent lacunar strokes. Lancet. 2013;382:507-15. doi: 10.1016/S0140-6736(13)60852-1.

31. Hansson L., Zanchetti A., Carruthers S.G., et al. Effects of intensive bloodpressure lowering and lowdose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. HOT Study Group. Lancet. 1998;351:1755-62. doi: 10.1016/S01406736(98)04311-6.

32. Julius S., Nesbitt S.D., Egan B.M., et al. Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 2006;354:1685-97. doi: 10.1056/NEJMoa060838.

33. Verdecchia P., Dagenais G., Healey J. et al. Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease Investigators. Blood pressure and other determinants of new-onset atrial fibrillation in patients at high cardiovascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease studies. J Hypertens. 2012;30:1004-14. doi: 10.1097/HJH.0b013e3283522a51.

34. Myers M.G., Godwin M., Dawes M., Kiss A.et al. Measurement of blood pressure in the office: recognizing the problem and proposing the solution. Hypertension. 2010;55:195-200. doi: 10.1161/HYPERTENSIONAHA.109.141879.

35. Lund-Johansen P. Hemodynamics in early essential hypertension. Acta Medica Scand. 1967;181(suppl. 482):2-101.

36. Mancia G., Bertinieri G., Grassi G., et al. Effects of blood-pressure measurement by the doctor on patient’s blood pressure and heart rate. Lancet. 1983;2:695-8. doi: 10.1016/S01406736(83)92244-4.

37. Filipovsky J., Seidlerova J., Kratochvil Z., et al. Automated compared to manual office blood pressure and to home blood pressure in hypertensive patients. J Blood Pressure. 2016;25(4):228-34. doi: 10.3109/08037051.2015.1134086.

38. Wohlfahrt P., Cifkova R., Movsisyan N., et al. Threshold for diagnosing hypertension by automated office blood pressure using random sample population data. J Hypertens. 2016;34:2180-6. doi: 10.1097/HJH.0000000000001076.

39. Drawz P., Pajewski N., Bates J. et al. Effect of intensive versus standard clinic-based hypertension management on ambulatory blood pressure results from the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory blood pressure study. Hypertension. 2016;69(1):42-50. doi: 10.1161/HYPERTENSIONAHA.116.08076.

40. Mancia G., Parati G. Office compared with ambulatory blood pressure in assessing response to antihypertensive treatment: a meta-analysis. J Hypertens. 2004;22:435-45.

41. Zanchetti A. White coat hypertension: the history of the irresistible, resistible ascent of a misnomer. In: Mancia G., Grassi G, Parati G, Zanchetti A, eds. White Coat Hypertension. Heidelberg, Germany: Springer; 2015:137-147.

42. Mancia G., Sega R., Bravi C., De Vito G. et al. Ambulatory blood pressure normality: results from the PAMELA study. J Hypertens. 1995;13(12 pt 1):1377-90.

43. Mancia G., Facchetti R., Parati G., Zanchetti A. Effect of long-term antihypertensive Treatment on white-coat hypertension. Hypertension. 2014;64:1388-98. doi: 10.1161/HYPERTENSIONAHA.114.04278.

44. Myers M., Kacsorowsky J., Paterson J.M., et al. Thresholds for Diagnosing Hypertension Based on Automated Office Ambulatory Blood Pressure Measurments and Cardiovascular Risk. Hypertension. 2015;66:489-495. doi: 10.1161/HYPERTENSIONAHA.115.05782.

45. George S., Stergiou G.S., Doumas M., et al. Important practice lessons from the SPRINT study beyond the blood pressure goal: All well-known and now confirmed. Journal of the American Society of Hypertension. 2016;16:1933-40. doi: 10.1016/j.jash.2016.06.002.

46. Smirnova MI, Gorbunov VM, Volkov DA, et al. Seasonal changes in hemodynamic parameters in patients with controlled arterial hypertension and high normal arterial pressure in two regions of the Russian Federation with different climatic characteristics. Part 3. Main results of the study of 1630 patients. Profilakticheskaja Medicina. 2015;18(6):78-86 (In Russ.) [Смирнова М.И., Горбунов В.М., Волков Д.А., и др. Сезонные изменения гемодинамических параметров у больных с контролируемой артериальной гипертонией и высоким нормальным артериальным давлением в двух регионах Российской Федерации с различными климатическими характеристиками. Часть 3. Основные результаты исследования 1630 пациентов. Профилактическая Медицина. 2015;18(6):78-86].

47. Kjeldsen S.E., Mancia G. Unobserved automated office blood pressure measurement in the Systolic Blood Pressure Intervention Trial (SPRINT): systolic blood pressure treatment target remains below 140 mmHg. Eur Heart J Cardiovasc Pharmacother. 2016;2(2):79-80. doi: 10.1093/ehjcvp/pvw002.