NEJM has just published SPRINT trial (systolic blood pressure intervention trial), a randomized, controlled, open-label trial that was conducted at 102 clinical sites (organized into 5 clinical center networks) which which compared the benefit of treatment of systolic blood pressure to a target of less than 120 mm Hg with treatment to a target of less than 140 mm Hg.
Let’s look at the overview of the study:
Increased CV risk is defined as
- clinical or subclinical cardiovascular disease other than stroke
- chronic kidney disease, excluding polycystic kidney disease, with an estimated glomerular filtration rate (eGFR) of 20 to less than 60 ml per minute per 1.73 m2 of bodysurface area, calculated with the use of the fourvariable Modification of Diet in Renal Disease equation
- a 10-year risk of cardiovascular disease of 15% or greater on the basis of the Framingham risk score
- an age of 75 years or older.
- An indication for a specific BP lowering medication (e.g., beta-blocker following acute myocardial infarction) that the person is not taking and the person has not been documented to be intolerant of the medication class. (If a screenee has a non-hypertension indication for a BP-lowering medication (e.g., beta-blocker post-MI, renin angiotensin system (RAS) blocker for CVD prevention, or alpha blocker for benign prostatic hypertrophy (BPH)), the screenee should be on the appropriate dose of such medication before assessing whether he/she meets the SPRINT inclusion criteria. If the investigator believes that a potential participant has such an indication but is not receiving appropriate treatment,
he/she should encourage the potential participant’s primary care provider to consider placing the patient on the appropriate therapy prior to proceeding with the screening process.)
- Known secondary cause of hypertension that causes concern regarding safety of the protocol.
- One minute standing SBP < 110 mm Hg. Not applicable if unable to stand due to wheelchair use.
- Proteinuria in the following ranges (based on a measurement within the past 6 months)
(a) 24 hour urinary protein excretion ≥1 g/day, or
(b) If measurement (a) is not available, then 24 hour urinary albumin excretion ≥ 600 mg/day, or
(c) If measurements (a) or (b) are not available, then spot urine protein/creatinine ratio ≥ 1 g/g creatinine, or
(d) If measurements (a), (b), or (c) are not available, then spot urine albumin/creatinine ratio ≥ 600 mg/g creatinine, or
(e) If measurements (a), (b), (c), or (d) are not available, then urine dipstick ≥ 2+ protein
- Arm circumference too large or small to allow accurate blood pressure measurement with available devices
- Diabetes mellitus. Participants taking medications for diabetes at any time in the last 12 months are excluded. Participants are also excluded if there is documentation of: FPG at or above 126 mg/dL, A1C ≥6.5 percent, a two-hour value in an OGTT (2-h PG) at or above 200 mg/dL or a random plasma glucose concentration ≥200 mg/dL. The diagnosis of diabetes must be confirmed on a subsequent day by repeat measurement, repeating the
same test for confirmation. However, if two different tests (eg, FPG and A1C) are available and are concordant for the diagnosis of diabetes, additional testing is not needed. If two different tests are discordant, the test that is diagnostic of diabetes should be repeated to confirm the diagnosis.
- History of stroke (not CE or stenting)
- Diagnosis of polycystic kidney disease
- Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
- eGFR < 20 ml/min /1.73m2 or end-stage renal disease (ESRD)
- Cardiovascular event or procedure (as defined above as clinical CVD for study entry) or hospitalization for unstable angina within last 3 months
- Symptomatic heart failure within the past 6 months or left ventricular ejection fraction (by
any method) < 35%
- A medical condition likely to limit survival to less than 3 years, or a cancer diagnosed and treated within the past two years that, in the judgment of clinical study staff, would compromise a participant’s ability to comply with the protocol and complete the trial. Exceptions to the exclusion for diagnosed cancer would include, for example, nonmelanoma
skin cancer, early-stage prostate cancer, localized breast cancer.
- Any factors judged by the clinic team to be likely to limit adherence to interventions.
- Failure to obtain informed consent from participant
- Currently participating in another clinical trial (intervention study). Note: Patient must wait until the completion of his/her activities or the completion of the other trial before being screened for SPRINT.
- Living in the same household as an already randomized SPRINT participant
- Any organ transplant
- Unintentional weight loss > 10% in last 6 months
- Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using
- Patients<50, with diabetes and stroke were not included.
- Physicians, patients, interviewers were not able to be blinded from the group allocations. However, the commitee members reviewing the outcome were.
- Trial was terminated earlier (3.26 years instead of the 5 years intended).
- Only ~40% used statin and ~50% used aspirin.
- This is a trial where we can rely on the primary outcome. HRs calculated were not much different.
- Intensive regimen causes more risk of >30% reduction in eGFR (HR 3.49, CI 2.44-5.10, p<0.001) and microalbuminuria (HR 2.41, CI 0.63-1.04), p = 0.10)
- Significantly high rate of hypotension and AKI in intensive group.
- NNT at the end of 3.26 years = 60; compare this to NNH at the end of 3.26 years for primary outcome = ~80.
Comparison with the meta-analysis just published in The Lancet:
- Mean SBP in the intensive group is 133 mmHg (closer to the standard group mean BP = 134.6 mmHg in SRPINT trial)
- They found significant reduction in CV outcomes (myocardial infarction, stroke, heart failure, or cardiovascular death), MI, stroke), borderline (no statistically significant) reduction in HF, ESRF and CV death.
In conclusion, I agree with the author. A more strict BP maybe better in patients with high CV risk. The presence of J-curve in Bp control is still up for debate. However, the adv effects seen (hypotension and AKI) are also matters of concern.
Xinfang Xie et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic
review and meta-analysis. The Lancet, Nov 2015.
The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. NEJM Nov 2015.