In clinical practice in the office, it is difficult to match "atmosphere" of study for BP recording. However, one must try. fww
SPRINT: A Trial of Intensive Blood Pressure Lowering
SPRINT: A Trial of Intensive Blood Pressure Lowering
- Allan S. Brett, MD
Treating to a systolic target of 120 mm Hg lowered the incidence of adverse cardiovascular events in a high-risk population.
- Allan S. Brett, MD
For years, clinicians have debated how far to lower blood pressure (BP) in hypertensive patients. The multicenter Systolic Blood Pressure Intervention Trial (SPRINT) now provides some guidance.
SPRINT researchers enrolled 9361 patients (age, ≥50) with systolic BP of 130 to 180 mm Hg and high cardiovascular (CV) risk (defined as one or more of these: known symptomatic or asymptomatic CV disease, chronic kidney disease [CKD] with glomerular filtration rate [GFR] 20–59 mL/minute/1.73 m2, 10-year Framingham CV risk ≥15%, or age ≥75). Patients with diabetes and stroke were excluded. Patients were randomized to either intensive or standard treatment (systolic BP targets, 120 or 140 mm Hg, respectively). The protocol included general guidelines for choice of antihypertensive agents, but researchers were permitted discretion in choosing drug regimens. Diuretics, angiotensin-converting–enzyme inhibitors or angiotensin-receptor blockers, calcium-channel blockers, and β-blockers were used extensively. During the trial, intensive- and standard-treatment patients required averages of three and two drugs, respectively.
The trial was terminated early after median follow-up of 3.3 years, during which participants' average systolic BPs were 121.5 mm Hg and 134.6 mm Hg in the intensive- and standard-treatment groups, respectively. The primary composite outcome (myocardial infarction [MI], non-MI acute coronary syndrome, stroke, heart failure, or CV-related death) occurred in 5.2% of intensive-treatment patients and 6.8% of standard-treatment patients (P<0.001). Relative reductions in this outcome were similar in subgroups of patients with CKD and of patients older than 75. Two individual components of the composite outcome were significantly lower with intensive treatment — heart failure (1.3% vs. 2.1%) and CV-related death (0.8% vs. 1.4%). All-cause mortality also was significantly lower with intensive treatment (3.3% vs. 4.5%).
Several serious adverse events were significantly more common with intensive than with standard treatment: Incidences of hypotension, syncope, and electrolyte abnormalities were each about 1 percentage point higher, and incidence of acute kidney injury was about 2 percentage points higher. Among patients without CKD at baseline, the incidence of a >30% decline in GFR was significantly greater with intensive treatment (3.8% vs. 1.1%).
Comment — General Medicine
SPRINT has demonstrated that aiming for a systolic BP of 120 mm Hg can lower the rate of adverse cardiovascular events; to prevent 1 event, 61 patients had to be treated for 3.3 years. Keep in mind that SPRINT was limited to middle-aged and older patients at above-average CV risk and that diabetic patients were excluded because the ACCORD BP researchers had examined this question (and showed no significant lowering of adverse CV events with intensive treatment; NEJM JW Cardiol Apr 2010 and N Engl J Med 2010; 362:1575). Whether the decline in GFR associated with intensive treatment represents a harmless hemodynamic effect or more-serious renal injury is unclear.
Because this trial will change practice, clinicians must understand how BP was measured in the study. At each visit, patients were seated in a quiet area for 5 minutes. Then, BP was recorded by a commercially available automated unit that recorded three readings, separated by several minutes, with no clinician in the room. Decisions were based on the average of the three readings. Other studies have shown that this method of BP measurement yields substantially lower readings than does the single rushed measurement typical in many practices. If SPRINT is applied without attention to proper BP measurement, substantial overtreatment — with a higher rate of adverse events — likely will occur.
Finally, note that the average achieved systolic BP in the intensive-treatment group (121.5 mm Hg) remained higher than the 120 mm target. This likely represents judicious balancing by treating clinicians who tried to approximate the 120 mm goal while avoiding side effects and excessive polypharmacy. Thus, an editorialist concludes reasonably that “the results from SPRINT warrant reducing the treatment goal for systolic blood pressure to less than 130 mm Hg” in patients who meet SPRINT's enrollment criteria.
Comment — Cardiology
- Harlan M. Krumholz, MD, SM
The study is excellent and opens up the option of additional treatment for a subgroup of hypertensive patients whose systolic blood pressure remains above 130 mm Hg. The original press conference and press coverage emphasized relative reduction in risk, but this publication reveals much more nuance. The benefits are impressive (although incidence of stroke appeared to be similar in both groups), but treating to these BP goals is associated with important risks, including life-threatening hypotension, syncope, and kidney injury or failure. Ultimately, we will need more information about which patients experience the greatest benefit and the least risk. For now, the challenge for doctors will be to remember that this trial is not a mandate for treatment but evidence to inform decisions about a new option. Personalizing the decision for each patient's preferences and circumstances will be important.
Editor Disclosures at Time of Publication
Disclosures for Allan S. Brett, MD at time of publication Nothing to disclose
Reader Comments (10)
Though the study appears to have rigorous, I conclude that the use of electronic blood pressure monitors without indicating how those monitors were certified is suspect. Evidence of the falability of such monitors exists throughout the current literature. Could a head to head comparison of manual to electronic BP measurement be considered whether than the assumption that manual measurement is considered to be to cumbersome and complicated thereby eliminating it as effective.
The study included high CV risk category patients excluding diabetics for obvious reason. I have certain doubts about the way it was conducted and abruptly withdrawn. Why not compare effect of diet, exercise and yoga therapy in half of the patients instead of subjecting them to 3 drug intensive therapy regime? Patient selection criteria could be on the basis of BMI and not random. High BMI crowd are likely to respond to strict dirlary and exercise - induced weight control regime. I wished the researchers had chosen this route instead of adding another drug (3rd drug). This will naturally raise eyebrows on the motive of such a trial... all the more reason it casts a shadow when the press is informed about the study result prematurely to give an impression that a revolutionary improvement had been achieved in the way doctors should set their targets for all hypertensive clients which is grossly misplaced. I wonder if meticulous peer review was put in place before such press release is made to happen...if not...it smells of a motivated self- promotion by these rearchers to obtain undue favor from pharma companies...at least the impression of this kind is generated with the hasty manner they conducted it and then withdrew their study. Not very convincing for me.
A good thought provoking study.How far applicable to Indians time only can tell us.But I will henceforth try to bring our BPb target lower than I tried earlier.
Many studies yield a number needed to harm greater than a number needed to treat. However, we must remember that the outcomes of harm and the outcomes of treatment are very different. In this case, outcomes of MI, stroke and CV-related death are much "harder", more detrimental outcomes that incidences of hypotension, electrolyte abnormlities, etc.
The only problem that I see, it is that SPRINT, was stopped early.We do not know what could happen with more years of observation.Besides this, if the results arecorrect,in the future will exist a problem, with the adhesivity of patients to treatment. We know, in Nephrology, that the lost of Kidney graft,in 50%, it is produced by sotopping treatment by patients.
Unfortunately this study was reported in the media without the
nuances described in the comments/conclusion expressed above.
The impression was that this was the new standard for BP control
for the population in general. We wonder why our patients are
confused. As a profession we need to make the significance of such studies understandable or lose further credibility.
Looking at the absolute risk reduction numbers for the primary composite outcome, the number needed to treat appears to be 62. While the number needed to harm is about 33 ("Incidences of hypotension, syncope, and electrolyte abnormalities were each about 1 percentage point higher, and incidence of acute kidney injury was about 2 percentage points higher")
It is difficult to tell a patient that there is a less than 2% chance that more intensive BP lowering might be beneficial, but that it is twice as likely that they could have a serious side effect.
Am I missing something here?
The NNT for the SPRINT study is 61. From a public health standpoint, given the fact that 70 million Americans have hypertension, more intensive treatment may be warranted. But, from an individual standpoint, it's a hard sell. I'm supposed to tell my patient that he/she needs to be treated with three medications and have a higher risk of significant side effects to achieve a one-in-61 chance of being benefited. I, personally would not choose to be so treated.
Adverse effects with more intensive treatment are significant. a NNH for acute kidney injury of 50 is certainly worrisome. In addition, I saw no mention of sexual side effects. Are the authors unaware that many of us over-fifties continue to have sex?
Studies that are terminated early are always suspect. Hopefully this study will not change practice as it will likely lead to an increase in hypotension-related adverse effects especially in the elderly (see www.anvita.info/wiki/Systolic_Hypertension & www.anvita.info/wiki/Blood_Pressure_In_The_Very_Old). Especially worrisome are effects on cognition... I don't see any discussion of diet & exercise vs drugs.., or is it all about selling drugs?