Final SPRINT: Keeping BPs under 120 mmHg Optimizes CV Risk Reduction

A new and final analysis of the SPRINT trial has borne out the results from the original study from 2015: Intensive blood pressure (BP) lowering in patients at increased cardiovascular (CV) risk to ˂120 mmHg significantly reduced the incidence of major adverse CV events and lowered all-cause mortality compared with lowering BP to a target of ˂140 mmHg during and after treatment. Adverse events, however, were more common with intensive BP lowering.

Results of the final analysis are published in The New England Journal of Medicine.

One of the most important hypertension trials ever conducted—with results eagerly awaited—the Systolic Blood Pressure Intervention Trial (SPRINT) was the largest of its kind, and was designed to assess whether intensive BP lowering was associated with a lower rate of CV events than standard treatment. The study, in part, was in response to controversial guideline updates from the Eighth Joint National Committee (JNC 8) relaxing recommendations for systolic BP treatment thresholds from ≤140 to <150 mmHg for patients aged 60 years and older.

SPRINT researchers included 9,361 patients at increased risk for CVD but without diabetes or previous stroke who adhered to an intensive systolic blood-pressure control treatment target (systolic BP ˂120 mmHg) or the standard treatment target (systolic BP ˂140 mmHg). The primary outcome of SPRINT was a composite of MI, other acute coronary syndromes, stroke, acute decompensated heart failure (HF), or death from CVD causes.

The cohort included high numbers of three groups of patients who were at particularly high risk: African Americans, patients with chronic kidney disease, and the elderly (≥75 years). The three first-line hypertensive agents used included chlorthalidone, amlodipine, and either an ACE inhibitor or an ARB—drugs all recommended by every recent guideline published at the time.

But disappointingly, the SPRINT trial was halted six months early—in October 2015—due to the significant benefit seen with intensive BP lowering, with decreases in both the rate of major CV events by nearly one-third, and the risk of death by almost 25% in patients at high CV risk.

Researchers have now circled back to the results after adjudicating original results and including post-trial follow-up data. They adjudicated primary outcome events that occurred through the end of the intervention period, Aug. 20, 2015, and analyzed post-trial observational follow-up data through July 29, 2016.

Patients in the intensive-treatment group had a significantly lower rate of the primary outcome and all-cause mortality after a median of 3.33 years of follow-up compared with those in the standard-treatment group (primary outcome: 1.77% per year versus 2.40% per year; HR: 0.73; 95% CI: 0.63-0.86; and all-cause mortality: 1.06% per year versus 1.41% per year; HR: 0.75; 95% CI: 0.61-0.92). These results were both similar to previously published findings.

Cora E. Lewis, MD, MSPH, of the University of Alabama at Birmingham, and fellow SPRINT researchers analyzed combined intervention and post-intervention results, and found that the primary outcome and mortality rates were still significantly lower in patients receiving intensive therapy compared with standard (HR for primary outcome: 0.76; 95% CI: 0.65-0.88; P˂0.001; HR for death: 0.79; 95% CI: 0.66-0.94; P=0.009), as were the rates of MI (HR: 0.71; 95% CI: 0.56-0.90; P=0.005, and rates of CV mortality (HR: 0.65; 95% CI: 0.46-0.90; P=0.01). The rates of heart failure events were not significantly different.

In patients with chronic kidney disease (CKD) at baseline, researchers found no significant difference in the renal composite outcome (≥50% reduction in estimated glomerular filtration rate [eGFR], dialysis, or kidney transplantation) between the intensive and standard treatment groups. However, in patients without baseline CKD, they observed that a 30% reduction in eGFR to ˂60 ml/min/1.73 m²) occurred significantly more often in patients treated with intensive therapy compared with standard treatment (HR: 3.67; 95% CI: 2.62-5.26; P˂0.001).

During the intervention period, Lewis et al found no significant differences in serious adverse events when comparing the intensive and standard treatment groups, but hypotension (2.1% versus 1.2%, respectively; P=0.001), electrolyte abnormalities (2.9% versus 2.2%; P =0.03), acute kidney injury or failure (4.1% versus 2.5%; P ˂0.001), and syncope (3.2% versus 2.1%; P=0.002) occurred significantly more frequently in the intensive-treatment group. The same was true when they did a combined analysis of intervention and postintervention data.

“In this final report of the main outcomes of the SPRINT trial, involving patients at increased risk for cardiovascular events, intensive treatment to lower blood pressure was associated with lower rates of fatal and nonfatal cardiovascular events and death from any cause than standard treatment. However, some adverse events occurred more frequently with the lower blood-pressure target. During a post-trial observational period, the achieved blood-pressure differential between the treatment groups was attenuated, and more frequent heart failure was noted in the intensive-treatment group,” concluded Lewis and colleagues.

1. In patients at increased cardiovascular risk, intensive blood pressure lowering to less than 120 mmHg significantly decreased major adverse cardiovascular events and lowered all-cause mortality, according to results from the final analysis of the SPRINT trial.

2. Compared with a targeted blood pressure of less than 140 mm Hg, lowering BP to less than 120 mm Hg resulted in significant benefits.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

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Topic ID: 74,6,730,6,914,127,410,192,916,925