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One nephrologist's thoughts on where in the annals of hypertension trials the SPRINT results may settle.
Evaluating the impact of hypertension trials is similar to predicting hurricanes. A potential hurricane may lose wind force and become a tropical storm. Some hypertension trials have been hurricanes (ASCOT, STOP-1, or SHEP for example)-radically changing what clinicians do with high blood pressures on a daily basis. But others have lost force. Where does SPRINT1 fit into the hurricane-tropical storm analogy? Let's summarize SPRINT's results first. After that, we will measure the “wind speed” of the study’s conclusions and ask whether any or all of its suggested implications will find their way into clinical practice.
Gregory W. Rutecki, MDSince hypertension is a global risk factor for myriad vascular complications (high blood pressure kills more people than tobacco)2 what was SPRINT looking to prove? The earliest hypertension trials addressed persons with moderate to severe blood pressure elevations and benefits of antihypertensive treatment were clearly demonstrated.3 But there is a log-linear relationship between blood pressure and complications beginning at blood pressure levels well below 140/90 mm Hg.3 A recent Framingham “offspring” study demonstrated excess cardiovascular risk for persons whose baseline systolic pressure was higher than normal, but not high enough by present guidelines to warrant initiating pharmacologic treatment.3 As a result, contemporary trials are asking a critical question as an extension of saying lowering blood pressure is a good thing: “how low should we go when we lower blood pressure to prevent complications?” What we are learning in that process is that this question must be balanced by another: Do lower blood pressure targets harm patients more than they help (eg, falls from orthostatic hypotension or electrolyte abnormalities)?
Systolic Blood Pressure Intervention Trial
SPRINT (n=1627 hypertensive persons without diabetes or prior strokes, but with increased cardiovascular risk, and aged >50 years) was comprised of 2 study groups, both treated for hypertension-those treated to lower or higher systolic blood pressure targets of <120 vs <140 mm Hg, respectively. The primary outcome measures included acute coronary syndromes with or without myocardial infarctions, stroke, acute heart failure, or death from cardiovascular events. It is important to note that blood pressures were measured in a novel way during the SPRINT trial. An average of 3 consecutive “unattended” (that is, no healthcare professional in the room) automated measurements was used with patients seated, after resting for 5 minutes. Let’s summarize the good as well as the potentially more controversial portions of SPRINT:
1. The p value was significant for decreased heart failure and cardiovascular events in the lower systolic versus higher SPRINT blood pressure target groups. The SPRINT trial was stopped early because of this positive outcome. Yes, this is an important and beneficial outcome.
2. Chlorthalidone and amlodipine were favored as therapeutic agents. Chlorthalidone has been a potent agent in hypertension treatment for many years and in this author’s opinion, is underused, especially as a substitute for hydrochlorthiazide in persons with renal disease.
3. Considerable reliance on SPRINT informed the Canadian Hypertension Education Program to recommend lower target systolic blood pressures in high risk individuals for their guidelines and use of an automated office blood pressure device for measurements in the future.4
1. Despite the benefits of intensive treatment, one would need to treat 1000 people to a systolic pressure of ≤120 mm Hg to benefit 16.5
2. Lower study blood pressures (the ≤120 mm Hg group) were associated with a greater incidence of syncope, electrolyte abnormalities, and acute renal injury with more frequent visits to the emergency department despite the fact that frail elderly in assisted living facilities were excluded from SPRINT.6
3. The p value comparing the lower blood pressure target group to the higher was insignificant for stroke and myocardial infarctions.1
4. In daily practice, it may be difficult to apply SPRINT to various patients in light of its discordance with other studies. For example, ACCORD--which addressed the lower versus higher systolic blood pressure targets specifically in diabetics--did not demonstrate a benefit of achieving lower systolic targets in this demographic. If you were to apply SPRINT’s lower targeted blood pressure in individuals with CKD, there were not enough patients with CKD enrolled in the trial to justify the lower target in this demographic either.2,5,6,7
5. Heated discussion at the European Society of Cardiology Congress in August inlcuded dmeands that SPRINT findings not be used by guidelines committees to suggest lower blood pressure targets.8
6. One half of the 120-mm-Hg-systolic-target group in SPRINT did not maintain the goal blood pressure.6 This fact begs the question of the feasibility of lower blood pressure targets. Would lower targets be something busy clinicians can cope with?
7. Only 30% of enrolled SPRINT patients were in the ≤120 mm Hg arm.6
First, quantity is not quality. The 7 controversial issues with SPRINT should not outweigh the 3 good. The benefits accrued in the lower systolic target arm of SPRINT-that is, less heart failure and cardiovascular events-is an important finding. Obviously, the Canadian Blood Pressure Study Group thinks so. Said another way, the jury still out on SPRINT. Or, returning to the hurricane analogy, right now, it may be that the SPRINT results should be downgraded to a tropical storm, until it or other studies demonstrate other benefits-in disparate groups (CKD7 or diabetes)-of lower BP targets. It also allows time for specialists and primary care providers alike to consider the time constraints of targeting and maintaining lower targets. It won’t be easy.
1. SPRINT Research Group. A randomized trial of intensive versus standard blood pressure control. N. Engl. J. Med. 2015; 373:2103-2016.
2. Campos K, Sheth S, Coulter SA. Hypertension treatment ACCORDing to SPRINT. Texas Heart Institute J. 2016; 43:324-327.
3. Flack JM, Nolasco C, Levy P. The case for low blood pressure targets. Am. J. Hypertens. 2016; doi:10.1093/ajh/hpw087.
4. Leung AA, Nerenberg K, Daskalopoulou SS, et al. Hypertension Canada’s 2016 Canadian Hypertension Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol. 2016;32:569-588.
5. Thomas, G. 17th Annual Intensive Review of Cardiology, Comprehensive Update and Advances; August 21-24, 2016. Cleveland Clinic Heart and Vascular Institute.
6. Bhatt H, Ghazi L, Calhoun D, Oparil S. BP targets in hypertension: what should we do now that SPRINT is out? Curr. Cardiol. Rep. 2016; 18: 98.
7. Covic C, Apetrii M, Goldsmith D, Kanbay M. SPRINT: The study nephrologists might take with a grain of salt. J Clin. Hypertens. 2016; doi:10.1111/jcgh.12866 [e pub].
8. Husten L. CardioBrief: Cardiologists give SPRINT thumbs down. Medpage Today. August 29, 2016. Acessed on September 14 and availalbe at: http://www.medpagetoday.com/meetingcoverage/esc/59908