Portal de Periódicos da CAPES

Unattended Blood Pressure Measurements in the Systolic Blood Pressure Intervention Trial

2016; Lippincott Williams & Wilkins; Volume: 67; Issue: 5 Linguagem: Inglês

10.1161/hypertensionaha.116.07257

1524-4563

Sverre E. Kjeldsen, Per Lund‐Johansen, Peter M. Nilsson, Giuseppe Mancia,

Cardiovascular Health and Disease Prevention

HomeHypertensionVol. 67, No. 5Unattended Blood Pressure Measurements in the Systolic Blood Pressure Intervention Trial Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUBUnattended Blood Pressure Measurements in the Systolic Blood Pressure Intervention TrialImplications for Entry and Achieved Blood Pressure Values Compared With Other Trials Sverre E. Kjeldsen, Per Lund-Johansen, Peter M. Nilsson and Giuseppe Mancia Sverre E. KjeldsenSverre E. Kjeldsen From the Department of Cardiology, University of Oslo, Ullevaal Hospital, Oslo, Norway (S.E.K.); Department of Heart Diseases, University of Bergen, Haukeland Hospital, Bergen, Norway (P.L.-.J.); Department for Clinical Sciences, University of Lund, Malmö, Sweden (P.M.N.); and IRCCS Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy (G.M.). , Per Lund-JohansenPer Lund-Johansen From the Department of Cardiology, University of Oslo, Ullevaal Hospital, Oslo, Norway (S.E.K.); Department of Heart Diseases, University of Bergen, Haukeland Hospital, Bergen, Norway (P.L.-.J.); Department for Clinical Sciences, University of Lund, Malmö, Sweden (P.M.N.); and IRCCS Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy (G.M.). , Peter M. NilssonPeter M. Nilsson From the Department of Cardiology, University of Oslo, Ullevaal Hospital, Oslo, Norway (S.E.K.); Department of Heart Diseases, University of Bergen, Haukeland Hospital, Bergen, Norway (P.L.-.J.); Department for Clinical Sciences, University of Lund, Malmö, Sweden (P.M.N.); and IRCCS Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy (G.M.). and Giuseppe ManciaGiuseppe Mancia From the Department of Cardiology, University of Oslo, Ullevaal Hospital, Oslo, Norway (S.E.K.); Department of Heart Diseases, University of Bergen, Haukeland Hospital, Bergen, Norway (P.L.-.J.); Department for Clinical Sciences, University of Lund, Malmö, Sweden (P.M.N.); and IRCCS Istituto Auxologico Italiano, University of Milano-Bicocca, Milan, Italy (G.M.). Originally published21 Mar 2016https://doi.org/10.1161/HYPERTENSIONAHA.116.07257Hypertension. 2016;67:808–812Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2016: Previous Version 1 The Systolic Blood Pressure Intervention Trial (SPRINT) enrolled 9361 participants aged ≥50 years in ≈100 expert medical centers and clinical practices throughout the United States.1 SPRINT excluded patients with diabetes mellitus and stroke survivors since previous clinical trials included those populations.2,3 Between 2010 and 2013, the SPRINT investigators randomly allocated the study participants into a standard treatment group receiving an average of 2 different blood pressure (BP) medications to achieve a systolic BP (SBP) target <140 mm Hg and into an intensive treatment group receiving an average of 3 BP medications to achieve a SBP target <120 mm Hg. The Director of the National Heart, Lung, and Blood Institute stopped SPRINT early because of a positive effect. The significant preliminary results of SPRINT were announced on September 11, 20154 and the study results were quickly and favorably commented on by the New York Times5 and the Washington Post.6 The target SBP <120 mm Hg had reduced rates of the composite primary outcome that included myocardial infarction (MI), other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes by 25% and the risk of death from all causes by 27%, when compared with the target SBP of <140 mm Hg. The primary results of the trial were presented at the Scientific Sessions of the American Heart Association in Orlando on November 9, 2015 and published on the same day.7 The SPRINT study was published with an accompanying statement from the Editor of New England Journal of Medicine8 saying that "This clinical trial will change practice, and we are proud to publish it and to defend the importance of the expedited peer-review and publication process that it has undergone. The report is now in the public domain, and the investigators' data interpretation, analysis, and clinical discussion are open to examination and comment."However, whether the results of the SPRINT study can be implemented into guidelines for the treatment of hypertension and clinical practice for the purpose of aiming at a lower target for SBP than the current SBP target of <140 mm Hg has yet not been settled. In this article, we aimed to review the measurement techniques for BP that was used in SPRINT and assess whether it is representative and applicable for practice outside the specific study. The reason for why we focus on the BP measurement technique in SPRINT is that if it varies substantially from other trials of similar design and aims, the results of SPRINT can only be included into hypertension guidelines and clinical practice with considerable reservation and utmost care. Similarities and differences with the Action to Control Cardiovascular Risk in Diabetes (ACCORD),2 Secondary Prevention of Small Subcortical Strokes (SPS3),3 and Hypertension Optimal Treatment (HOT)9 studies, the other large outcome trials investigating BP targets, are therefore needed to discuss. At present, there are no data from randomized outcome-based trials on home and ambulatory blood pressure targets or BP variability. Therefore, a discussion on target blood pressure values in different trials and guidelines can only refer to office blood pressure.Similarities With the ACCORD, SPS3, and HOT StudiesThe design and the results of SPRINT could in many aspects be compared with those of the US National Institutes of Health sponsored ACCORD study, which randomized hypertensive patients with type 2 diabetes mellitus to the same SBP targets as in SPRINT and did not find statistically significant benefit in the intensive treatment group.2 ACCORD enrolled a study population less than half the size of SPRINT that was younger than the SPRINT population and had normal renal function. Furthermore, ACCORD had a factorial design that included cholesterol and glucose-lowering treatments as well as BP reduction. For all these reasons, ACCORD was statistically underpowered to show a significant benefit of intensive BP reduction. However, ACCORD did show an 11% trend favoring the target SBP <120 mm Hg compared with <140 mm Hg for the composite primary end point and a significant 41% stroke reduction. These results suggest that the ACCORD study should be repeated with sufficient statistical power because there is a rationale for testing a rather aggressive treatment target in patients with type 2 diabetes mellitus, as previously suggested by a subgroup analysis of 1501 participants with diabetes mellitus in the HOT study.9Stroke survivors were also excluded from SPRINT because they were studied in the SPS3 study3 in which 3020 patients averaging 63 years with recent lacunar strokes were randomized to target SBP <130 versus <140 mm Hg and followed for an average of 3.7 years. The more intensive treatment reduced the rate of recurrent stroke by 19%, which did not reach statistical significance (P=0.08). However, intracerebral hemorrhages were reduced by 63% (P=0.03), and it can easily be suggested that SPS3, similar to ACCORD,2 was statistically underpowered. In the need for more outcome research of target BP in this kind of population, such patients are currently included into the ongoing European–Chinese randomized SHOT trial.10At variance from SPRINT, ACCORD, and SPS3, the HOT study randomized patients to diastolic BP (DBP) treatment targets ≤80, ≤85, and ≤90 mm Hg9 and was amazingly with n=18 700 patients also underpowered despite 1-year extention. HOT was organized to investigate the optimal target DBP to prevent MI, although investigated as a component of the primary end point. The treatment arms achieved average DBPs of 81, 83, and 85 mm Hg and the 215 patients with MIs favored lower BPs with borderline statistical significance (P=0.05). The low number of patients with end point was in contrast to the expected 500 MIs by the protocol or the 800 MIs if these patients had been left untreated with an average DBP of 105 mm Hg. It derives thereof that if the statistically significant result of such a trial is to be implemented, the absolute risk reduction, and accordingly the number needed to treat would be large. In fact, if the trial was large enough statistical significance is likely possible for even the most trivial differences. Guideline writers and the regulatory authorities may not embrace turning such statistically significant results into recommendations for the public good or approvals for medication use. However, HOT9 provided necessary new information on study design in this context, and a fundament so the subsequent trials ACCORD,2 SPS3,3 and SPRINT7 have shifted to SBP targets with differences of 20 mm Hg in ACCORD and SPRINT and 10 mm Hg in SPS3. The latter corresponds to a difference of 5 mm Hg for DBP in HOT, whereas 20 mm Hg corresponds to the difference between target groups ≤80 and ≤90 mm Hg in HOT.9Unobserved and Observed Automated Office Blood Pressure MeasurementsBeyond the lack of statistical power in ACCORD,2 SPS3,3 and HOT,9 another obvious common feature of these trials would for various reasons be the methods for measurement of BP. Simply because all trials were underpowered, one would wonder whether poor or imprecice BP measurement technique could add to the shortcomings, and whether SPRINT differed in this aspect? On the other side, all trials aimed at treating large number of people with high BPs to clearly defined BP targets, and by doing this involving hundreds of centers in various countries. It would thus on the contrary be expected that all the trials aimed to perform precise and well-standardized measurements of BPs. By scrutinizing the main papers2,3,7,9 and available protocols, the devices that were made available for investigators in the trials are listed in the accompanying Table. It would be beyond the scope of this brief review to comment on the quality of the various devices, but in all the main articles and protocols it is stated that the devices were validated and that they were well suited for the purpose of adjusting the participants' BPs to the randomized targets. In addition, there is no information published that participating centers did not use the BP devices provided by the study organizers. We have no evidence that all centers used the devices, but we must assume that the majority of them did use the devices, and that deviation from the study protocol in this respect was no issue to be mentioned in publications.Table. Automated/Semiautomated Devices Used for Measurements of Blood Pressure in Large Outcome Trials That Have Used the Automated Office Blood Pressure Measurement TechniqueTrialDeviceStatus of ObservationReferencesACCORDModel 907, Omron Healthcare, Lake Forest, ILAttendedThe ACCORD Study Group2SPS3Colin BP-8800C, Press Mate, Meena Medical Inc, Bedford, TXAttendedThe SPS3 Study Group3SPRINTModel 907, Omron Healthcare, Lake Forest, ILUnattendedThe SPRINT Research Group7HOTVisomat OZ, D2 International, Hestia Pharma GmbH, GermanyAttendedHansson et al9TROPHYHEM-705CP, Omron Healthcare, Lake Forest, ILAttendedJulius et al19ONTARGETHEM-757, Omron Corporation, Tokyo, JapanAttendedVerdecchia et al20TRANSCENDHEM-757, Omron Corporation, Tokyo, JapanAttendedVerdecchia et al20For optimal standardization people are seated in a quiet room for 3 to 5 minutes without talking before measurements are taken as an average of 3 measurements with 1 minute apart. Measurements have been done unattended (unobserved) and fully automated in the SPRINT study (no other people in the room) while being attended (observed) in all other trials by investigator or technician who activated the device. ACCORD indicates Action to Control Cardiovascular Risk in Diabetes study; HOT, Hypertension Optimal Treatment study; ONTARGET, Ongoing Telmisartan Alone and in Combination With Ramipril Global Enpoint Trial; SPRINT, Systolic Blood Pressure Intervention Trial; SPS3, Secondary Prevention of Small Subcortical Strokes study; TRANSCEND, Telmisartan Randomized Assessment Study in Aceintolerant Subjects With Cardiovascular Disease study; and TROPHY, Trial of Preventing Hypertension study.Cushman et al,11 who were SPRINT investigators, have provided additional details about BP measurement technique in a subsequent editorial. They described that BPs in SPRINT were measured with patients seated in a quiet room without talking and taken as an average of 3 measurements with an automated device (Omron Healthcare, Lake Forest, IL) that was preset to wait 5 minutes before measurements.11 They further state that "BP measurements taken without observing these conditions are likely to overestimate BP and result in overtreatment, with the potential for higher rates of serious adverse effects and greater ulilization of resources. This issue should be carefully considered in the development of any practice-based performance measures for BP control in hypertension that are derived from the SPRINT results." However, one essential detail is missing both in the main SPRINT publication7 and in the article of Cushman et al11 and that is the fact that measurements of BPs were done unattended or unobserved—that is, without an observer being present in the room. Although the statement "BP measurements taken without observing these conditions"11 could refer to such conditions, this statement could also have more generalized meaning and it is easy to misinterpret.However, the true details of the BP measurement technique in SPRINT are described beyond any point of misinterpretation in the editorial by the new editors of American Journal of Hypertension who are close to the SPRINT leadership12: "One aspect that has received only passing mention is the method of measurement of BP. This was performed using automated office BP measurement using an Omron device and measuring BP 3 times unobserved. This is critically important because SBP when measured this way may be 5 to 10 mm Hg lower than when measured with a manual instrument or even when patients are being observed or talking, or in a room that is not quiet. Thus in community practice, lowering SBP to 120 mm Hg may mean that, if not done according to the correct protocol of automated office BP, SBPs could actually be far lower than 120 mm Hg, with unknown consequences."All sites in SPRINT used the Omron 907, which was programmed for 5 minutes rest, and then BPs was measured 3× at 1-minute intervals. The Omron device was supplied by the study. The Manual of Operations and central training called for the study personnel to leave the room and the device was set to 5 minutes before starting the measurement (Jackson T. Wright, personal information). Thus, there is no doubt that measurements of BPs in SPRINT were performed fully automated and unobserved. Besides, participants in the intensive arm had their BP adjusted monthly for the first 3 months and later every 3 months, which is far more frequent than in usual clinical practice.Automated Office Versus Conventional Auscultatory Blood PressurePrevious studies in treated hypertensive people have shown that SBP by this automated office BP technique is comparable to, or even lower than daytime ambulatory SBP, and ≤20 mm Hg lower than conventional auscultatory SBP in the office.13 For generalization the number of mm Hg that should be added must be clarified; suggestions may vary from 5 to 10 mm Hg up to 10–20 mm Hg and a recent study14 done in 353 treated hypertensive people with BPs comparable with SPRINT indicates 16 mm Hg. Overall, it means that the lower treatment arm in SPRINT translates into SBP <136 mm Hg, which is not very different from SBP <140 mm Hg, which is the currently recommended SBP target by all hypertension treatment guidelines.Of the various devices used in the trials listed in Table, the Omron 907 is the only device that can be programmed to inflate after 5 minutes of seated rest. This could theoretically open for the possibility of unattended BP measurements also having been done in ACCORD. However, this is unlikely inasmuch as the technique of unattended measurements came in focus from about 2010,13 the year when ACCORD was published,2 and the protocols and protocol papers from ACCORD were published in 2007. We have again scrutinized all ACCORD papers, mostly published in 2007, and also the entire protocol including the final version of January 05, 2009, and there is nowhere, in these almost extremely detailed documents, any mentioning that people should leave the room during the BP measurements. Unfortunately, the ACCORD Manual of Operations is no longer available from the ACCORD website, but that the observers were not trained to leave the room while the Omron waited 5 minutes has been confirmed from the principal investigator (William C. Cushman, personal information).The BPTrue device (BpTRU Medical Devices Ltd, Coquitlam, BC, Canada) can also be programmed like the Omron 907; it was extensively validated in treated hypertensive people (n=353) and the difference averaged 16 mm Hg as mentioned above.14 About mandating the sitting period, this was standard in all trials, also trials not considered here, and could unlikely contribute to any difference in BP.The BP measurement technique that was used in SPRINT was thus different from the technique used in ACCORD, SPS3, and HOT in one key element, and that was the fact that other people were out of the room during measurements and the entire resting period before measurement. The SPRINT investigators thus were able to avoid the alert reaction or so-called "white-coat" effect and they may have circumvented the problem of white-coat hypertension. The alert reaction has been described in numerous ways throughout the years; an early observation was the rise in SBP by ≈10 mm Hg and in DBP by ≈6 mm Hg just by introducing a conventional cuff measurement of BPs on the opposite arm while continuously doing intra-aterial BP reading.15 These investigations were included in some of the earliest and most extensive hemodynamic studies of hypertensive people ever performed.15 The participants were quietly resting supine and they could not see the BP monitor with the intra-arterial readings, and this part of the investigations were not announced before being performed.15Similarly, in patients with mild hypertension intra-arterial mean BP increased by ≈20 mm Hg in reaction to physician's unexpected arrival at the bedside.16 In fact, SBP and DBP were peaking within 1 to 4 minutes by 27±2 and 15±2 mm Hg above previsit values, and they were still considerably elevated after 5 to 10 minutes.16 Such observer-dependent BP measurement may have a marked white-coat effect, and this is not avoided by waiting 5 minutes. In a subsequent study, the increase in intra-arterial BP associated with physician's measurement, although decreasing with the visit duration, was still on average of 12/7 mm Hg after 5 minutes and 11/4 mm Hg after 10 minutes, and virtually identical among 4 visits.17 This is not the case for automatic or semiautomatic measurements in the absence of an observer.18 BP was measured intra-arterially and on the contralateral arm by a noninvasive device (Vita-Stat 901; Vita-Stat Medical Devices, Inc, St. Petersburg, FL). For 2 hours, the device provided automatic cuff inflations at 10-minute intervals. For another 2 hours, it was programmed to provide cuff inflations only after patients' commands also at 10-minute intervals. Neither the automatic- nor the semiautomatic-induced cuff inflations caused increments in SBP and DBP.The unobserved measurements in SPRINT were no doubt intentional, both for the optimal standardization of measurements and for the quality of SPRINT, and to avoid the alert or white-coat effect without depending on ambulatory BP measurements. However, implications thereof are that BPs taken in SPRINT cannot be directly compared with BPs in other trials, and that the treatment arm goal 50 years of age to target SBP <120 versus <140 mm Hg, was stopped early because of effect in favor of <120 mm Hg. In SPRINT, measurements of BPs were exceptionally well standardized and taken in the office setting by a fully automated device after patients had been seated quietly without observer being present. This technique is at variance with the measurement techniques that were used in HOT, ACCORD, and SPS3, which were the previous prospective and randomized clinical trials to investigate the optimal BP targets to prevent cardiovascular complications. Most importantly, and the major difference, was that in SPRINT an observer was not present in the room because of the use of the fully preset and automated device, whereas in the previous trials observer was present in the room to activate the measurement device. The unattended measurements were no doubt intentional, both for the optimal standardization of measurements and for the quality in the trial, and to avoid the alert or white-coat effect without depending on ambulatory BP measurements. However, implications thereof are (1) BPs taken in SPRINT cannot be directly compared with BPs in other trials and (2) the treatment arm <120 mm Hg in SPRINT compares with a higher SBP value in the other trials. For generalization, the number of mm Hg that should be added must be clarified; suggestions vary from 5 to 10 mm Hg up to 10–20 mm Hg and a recent study indicates 16 mm Hg. Overall, it means that the lower treatment arm in SPRINT translates into SBP <136 mm Hg, not very different from SBP <140 mm Hg, which is the currently recommended SBP target for most hypertensive people by all hypertension treatment guidelines.DisclosuresS.E. Kjeldsen has received modest honoraria for consultancy and lecturing from Bayer, Merck & Co, and Takeda. G. Mancia has received honoraria for participation in international meetings as lecturer/chairman from Actavis, Bayer, Boehringer Ingelheim, Ferrer, Lilly, Medtronic, Menarini, Merck Serono, Novartis, Recordati, Sanofi, Servier, and Takeda. The other authors report no conflicts.FootnotesThis article was sent to David A. Calhoun, Guest Editor, for review by expert referees, editorial decision, and final disposition.Correspondence to Sverre E. Kjeldsen, Department of Cardiology, Oslo University Hospital, Ullevål, Kirkeveien 166, N-0407 Oslo, Norway. E-mail [email protected]References1. Ambrosius WT, Sink KM, Foy CG, et al; SPRINT Study Research Group. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT).Clin Trials. 2014; 11:532–546. doi: 10.1177/1740774514537404.CrossrefMedlineGoogle Scholar2. The ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus.N Engl J Med. 2010; 362:1575–1585. doi: 10.1056/NEJMoa1001286.CrossrefMedlineGoogle Scholar3. The SPS3 Study Group. Effects of blood pressure targets in patients with recent lacunar strokes.Lancet. 2013; 382:507–515. doi: 10.1016/S0140-6736(13)60852-1.CrossrefMedlineGoogle Scholar4. National Institutes of Health. Landmark NIH study shows intensive blood pressure management may save lives.http://www.nhlbi.nih.gov/news/press-releases/2015/landmark-nih-study-shows-intensive-blood-pressure-management-may-save-lives. Accessed September 12, 2015.Google Scholar5. Kolata G. Study testing blood pressure says go lower.New York Times. September 12, 2015.Google Scholar6. Bernstein L. Federal researchers urge older adults to aim for much lower blood pressure.Washington Post. September 12, 2015.Google Scholar7. The SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control.N Engl J Med. 2015; 373:2103–2116. doi: 10.1056/NEJMoa1511939.CrossrefMedlineGoogle Scholar8. Drazen JM, Morrissey S, Campion EW, Jarcho JA. A SPRINT to the Finish.N Engl J Med. 2015; 373:2174–2175. doi: 10.1056/NEJMe1513991.CrossrefMedlineGoogle Scholar9. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, Ménard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.Lancet. 1998; 351:1755–1762.CrossrefMedlineGoogle Scholar10. Zanchetti A, Liu L, Mancia G, et al. Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.J Hypertens. 2014; 32:1888–1897. doi: 10.1097/HJH.0000000000000254.MedlineGoogle Scholar11. Cushman WC, Whelton PK, Fine LJ, Wright JT, Reboussin DM, Johnson KC, Oparil S; SPRINT Study Research Group. SPRINT Trial Results: Latest News in Hypertension Management. Hypertension. 2016; 67:263–265. doi: 10.1161/HYPERTENSIONAHA.115.06722.LinkGoogle Scholar12. Schiffrin EL, Calhoun DA, Flack JM. SPRINT proves that lower is better for non-diabetic high-risk patients, but at a price.Am J Hypertens. 2016; 29:2–4. doi: 10.1093/ajh/hpv190.CrossrefMedlineGoogle Scholar13. Myers MG, Godwin M, Dawes M, Kiss A, Tobe SW, Kaczorowski J. Measurement of blood pressure in the office: recognizing the problem and proposing the solution.Hypertension. 2010; 55:195–200. doi: 10.1161/HYPERTENSIONAHA.109.141879LinkGoogle Scholar14. Filipovský J, Seidlerová J, Kratochvíl Z, Karnosová P, Hronová M, Mayer O. Automated compared to manual office blood pressure and to home blood pressure in hypertensive patients.Blood Press. http://dx.doi.org/10.3109/08037051.2015.1134086.Google Scholar15. Lund-Johansen P. Hemodynamics in early essential hypertension.Acta Medica Scand. 1967; 181(suppl 482):2–101.Google Scholar16. Mancia G, Bertinieri G, Grassi G, Parati G, Pomidossi G, Ferrari A, Gregorini L, Zanchetti A. Effects of blood-pressure measurement by the doctor on patient's blood pressure and heart rate.Lancet. 1983; 2:695–698.CrossrefMedlineGoogle Scholar17. Mancia G, Parati G, Pomidossi G, Grassi G, Casadei R, Zanchetti A. Alerting reaction and rise in blood pressure during measurement by physician and nurse.Hypertension. 1987; 9:209–215.LinkGoogle Scholar18. Parati G, Pomidossi G, Casadei R, Mancia G. Lack of alerting reactions to intermittent cuff inflations during noninvasive blood pressure monitoring.Hypertension. 1985; 7:597–601.LinkGoogle Scholar19. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, Black HR, Grimm RH, Messerli FH, Oparil S, Schork MA; Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker.N Engl J Med. 2006; 354:1685–1697. doi: 10.1056/NEJMoa060838.CrossrefMedlineGoogle Scholar20. Verdecchia P, Dagenais G, Healey J, et al; Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint TrialTelmisartan 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; 30:1004–1014. doi: 10.1097/HJH.0b013e3283522a51.MedlineGoogle Scholar21. Kjeldsen SE, Hedner T, Jamerson K, Julius S, Haley WE, Zabalgoitia M, Butt AR, Rahman SN, Hansson L. Hypertension optimal treatment (HOT) study: home blood pressure in treated hypertensive subjects.Hypertension. 1998; 31:1014–1020.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Reboldi G, Angeli F, Gentile G and Verdecchia P (2022) Benefits of more intensive versus less intensive blood pressure control. Updated trial sequential analysis, European Journal of Internal Medicine, 10.1016/j.ejim.2022.03.032, 101, (49-55), Online publication date: 1-Jul-2022. Jung H (2021) On-treatment blood pressure and long-term outcomes in chronic kidney disease, Nephrology Dialysis Transplantation, 10.1093/ndt/gfab151, 37:6, (1088-1098), Online publication date: 25-May-2022. Filippone E, Foy A and Naccarelli G (2022) Controversies in Hypertension II: the Optimal Target Blood