1. A Randomized Trial of Intensive versus Standard Blood-Pressure Control The SPRINT Research Group* November 9, 2015 10.1056/NEJMoa1511939 R2 이성곤 /pf. 우종신

2. Abstract Hypertension: highly prevalent in the US (≥ 60 yrs, 1 billion adults worldwide) ≥ 50 yrs, isolated systolic hypertension: most common SBP: independent risk predictor for coronary events, stroke, HF, & ESRD Tx. of HTN  Risk of cardiovascular disease outcomes↓, [incident stroke (by 35 ~ 40%), MI (by 15 ~ 25%), & HF (~ 64%)]

3. Background However, the target for SBP lowering is uncertain. Systolic Blood Pressure Intervention Trial (SPRINT)  Similar: SBP target of < 120 mm Hg & < 140 mm Hg but!> rate of stroke↓  Recent trial: SBP < 130 mm Hg vs < 150 mm Hg : no significant benefit of another stroke but! a significant benefit of risk of hemorrhagic stroke.

4. Method(1) Study Design and Oversight : Randomized, controlled, open-label trial 102 clinical sites in the US, including Puerto Rico. Study Population *Inclusion criteria ① At least 50 years old ② SBP i) 130 - 180 mm Hg: 0 or 1 medication ii) 130 - 170: ~ 2 medications iii) 130 - 160:~3medications iv) 130 – 150: ~4 medications

5. Method(2) ③ Risk (1 or more of the following) i) Clinical or subclinical cardiovascular disease other than stroke ii) CKD (eGFR of 20 ~ 59 ml/min/1.73 m 2 ) : MDRD(Modification of Diet in Renal Disease) equation iii) Framingham risk score a 10-year risk ≥ 15% iv) Age ≥ 75 years Clinical CVD: MI, PCI, CABG, CE, Carotid stenting/PAD c revasularization /ACS, EKG change(GXT), Cardiac imaging+/AAA ≥ 5cm Subclinical CVD: Calcium score ≥ 400, ABI ≤ 0.9, LVH (past 2yrs)

6. *Exclusion criteria: Specific BP lowering medication, 2ndary HTN, Proteinuira, DM or prior stroke, PCKD, etc… Randomization and Interventions SBP target < 140 mm Hg (the standard-treatment group) or < 120 mm Hg (the intensive-treatment group). Method(3) monthly for the 1 st 3 mo.  /3 mo. thereafter

7. Method(4) All major classes of antihypertensive agents were included (strongest evidence for reduction in cardiovascular outcomes) ① Thiazide-type diuretics (1st-line agent): e.g. Chlorthalidone ② Loop diuretics (for participants with advanced CKD) ③ BB (for those with CAD) ④ CCB(preferred amlodipine) ⑤ ACEi or ARB(e.g. Azilsartan) Mean of 3 BP measurements at an office visit ; seated and after 5 minutes of quiet rest ; automated measurement system. Lifestyle modification was encouraged

8. Method(5) Study Measurements Demographic data were collected at baseline. Clinical and laboratory data: at baseline and every 3 months thereafter. A structured interview: every 3 months, self-reported CVD outcomes. Serious adverse events : fatal or life-threatening  clinically significant or persistent disability that required or prolonged a hospitalization or medical or surgical intervention (e.g. hypotension, syncope, injurious falls, e’ abnormalities, & bradycardia// AKI or ARF)

9. Study Outcomes Primary outcome: major CVD events = 1 st occurrence of MI, non MI ACS, stroke, HF, or death from cardiovascular causes. Secondary outcome: = individual components of the primary composite outcome Renal outcomes: 1) with CKD(eGFR <60 ml/min/1.73 m 2 ) : eGFR ≥ 50% ↓, or  ESRD requiring long-term dialysis or KT. 2) without CKD: eGFR ≥ 30% ↓ or < 60 ml/min/1.73 m 2 Method(6)

10. Result Study Participants (2010.11~ 2013.3) (planned average of 5 yrs)

11. CVD (yes vs. no), CKD (yes vs. no), Sex, Race (black vs. nonblack), Age (<75 vs. ≥75), SBP in 3 levels (≤132, >132 ~ <145 mm Hg, & ≥145 mm Hg)

12. *The mean SBP: 1yr 121.4 mm Hg(intensive-group) 136.2 mm Hg(standard-group)  Average difference: 14.8 *3.26 years of f/u, The mean SBP: 121.5 mm Hg(intensive-group) 134.6 mm Hg (standard-group)] The mean number of BP medi. 2.8 and 1.8, respectively..

13. The mean DBP: 1 yr 68.7 mm Hg(intensive-group) 76.3 mm Hg(standard-group)

14. 562= 243 (1.65%/yr) intensive-group 319 (2.19%/yr) standard-group (HR, 0.75; 95% [CI]; P<0.001). 365 deaths 155(intensive-group) 210(standard-group) (HR, 0.73; 95% CI, ; P = 0.003) 43% lower (P = 0.005) intensive < standard Stopped early after a median f/u of 3.26 yrs ∵ primary outcome: intensive >> standard

15. No significant between-group difference, though the number of events was small. Intensive > Standard (1.21%/yr vs 0.35% / yr; P<0.001).

16. Primary outcome btw the groups was apparent at 1 yr Mortality btw the groups became apparent ≒ 2yrs

17. 1793 (38.3%)/1736 (37.1%) (HR 1.04; P = 0.25) *Hypotension, syncope, e’ abnormalities, and AKI or ARF : more frequently in the intensive treatment gruop *but not injurious falls or bradycardia, Significantly less common in the intensive-treatment group 220 (4.7%)/118 (2.5%)  possibly or definitely related to the intervention (HR, 1.88; P<0.001) ≥ 75 years : were similar to those in the overall cohort.

18. Conclusion SBP < 120 mm Hg, as compared with < 140 mm Hg, in patients at high risk for cardiovascular events but without diabetes  lower rates of fatal and nonfatal major cardiovascular events and death from any cause. However, some adverse events occurred significantly more frequently with the lower target.