Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes, writes MedicalBrief.
Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the New England Journal of Medicine. It includes data collected but not analysed when the primary analysis was released in 2015, as well as post-trial observational follow-up data collected through July 2016.
For the trial, researchers enrolled 9361 adults 50 years and older with an SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).
In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard treatment group (hazard ratio [HR], 0.73; 95% CI, 0.63 – 0.86; P < .001), similar to the earlier SPRINT findings. All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61 – 0.92; P = .006), again similar to the previous findings.
“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” The data confirm and enhance the earlier findings showing that “lower is better”, said lead author Prof Cora Lewis, Department of Epidemiology, University of Alabama at Birmingham School of Public Health..
She told Medscape that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group. “Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure.”
After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.
The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.
As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within a year”, Lewis said. “This and other analyses we have published indicate this is probably a haemodynamic effect. Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out of the window.”
Dr Carlos Santos-Gallego, from the Icahn School of Medicine in New York, said that original SPRINT trial had been “incredibly important” in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality, than targeting the conventional target of 140 mm Hg.
“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data.” However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of one extra year in which the treatment has been discontinued”.
“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients.” The potential adverse effects of intensive blood pressure control are “very manageable”, he added.
Support for SPRINT was provided by the National Institutes of Health (NIH). Full disclosures for authors are available in the original article.
Final Report of a Trial of Intensive versus Standard Blood-Pressure Control
Authors:The SPRINT Research Group*
Published on 20 May in the New England Journal of Medicine
In a previously reported randomised trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.
We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analysed post-trial observational follow-up data through July 29, 2016.
At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.
Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health).
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