Abstract
In a previously reported randomized 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.
Generated Summary
This study is a final report from the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial that investigated the effects of intensive versus standard systolic blood-pressure control on cardiovascular outcomes. The trial randomly assigned 9,361 participants at increased risk for cardiovascular disease, excluding those with diabetes or previous stroke, to either an intensive treatment target of <120 mm Hg or a standard target of <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. Data were collected during an intervention period and a subsequent observational post-intervention period. The research aimed to evaluate the long-term impacts of different blood pressure control strategies on cardiovascular health, mortality, and adverse events. The methods involved careful adjudication of events, statistical analysis using Cox proportional-hazards regression, and subgroup analyses to assess variations in treatment effects. The study included observational follow-up data to provide a comprehensive analysis of the long-term outcomes.
Key Findings & Statistics
- Primary Outcome: The rate of the primary outcome was significantly lower in the intensive-treatment group compared to the standard-treatment group during the intervention period (1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; P<0.001).
- All-Cause Mortality: All-cause mortality was also significantly lower in the intensive-treatment group (1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92; P=0.006).
- Serious Adverse Events: Serious adverse events overall did not differ significantly between the groups (1.04 (0.97-1.11) p=0.23)
- Myocardial Infarction: Rates of myocardial infarction were significantly lower in the intensive-treatment group (hazard ratio, 0.72; 95% CI, 0.56 to 0.93; P=0.01).
- Heart Failure: Death from cardiovascular causes were significantly lower in the intensive-treatment group (hazard ratio, 0.63 (0.46-0.86) p=0.003)
- Heart Failure: Heart failure was significantly lower in the intensive-treatment group (0.63 (0.46-0.86) p=0.003)
- Stroke: Rates of stroke were comparable between groups (hazard ratio, 0.89; 95% CI, 0.64 to 1.23; P=0.48).
- Post-Intervention Outcomes: The primary outcome continued to be lower in the intensive-treatment group (hazard ratio, 0.87; 95% CI, 0.59 to 1.27; P=0.46).
- Mortality: Overall, all-cause mortality was lower in the intensive-treatment group (hazard ratio, 0.75; 95% CI, 0.61 to 0.92; P=0.006).
- Hypotension: Hypotension, syncope, and electrolyte abnormalities were significantly more frequent in the intensive-treatment group. (1.71 (1.24-2.38) p=0.001)
- Syncope: Syncope was significantly more frequent in the intensive-treatment group. (1.33 (0.98-1.81) p=0.07)
- Electrolyte abnormalities: Electrolyte abnormalities were significantly more frequent in the intensive-treatment group.(1.33 (1.03-1.72) p=0.03)
- Acute Kidney Injury: Acute kidney injury or acute renal failure occurred more often in the intensive-treatment group (1.69 (1.34-2.13) p<0.0001)
- Renal Outcomes: Among participants without chronic kidney disease at baseline, the 30% or greater decline in eGFR was significantly more common in the intensive-treatment group (hazard ratio, 3.67; 95% CI, 2.62 to 5.26; P<0.001).
Other Important Findings
- Subgroup Analysis: The benefits of intensive treatment were generally consistent across subgroups, including those with or without previous cardiovascular disease, and across different age and racial groups.
- Medication Changes: In the post-intervention period, changes in blood pressure medication use differed between groups, which may have influenced the observed heart failure events.
- Post-Intervention Outcomes and intervention period: When intervention and post-intervention data were combined, the primary outcome and death rates remained significantly lower in the intensive-treatment group (hazard ratio for the primary outcome, 0.76; 95% CI, 0.65 to 0.88; P<0.001; hazard ratio for death, 0.79; 95% CI, 0.66 to 0.94; P=0.009).
Limitations Noted in the Document
- Observational Follow-up: The post-intervention data were observational, which may be subject to biases.
- Medication Adherence and Changes: The study did not strictly control medication adherence or changes in treatment during the post-intervention period.
- Heart Failure Events in post-Intervention: The event rate for acute decompensated heart failure was significantly higher in the intensive-treatment group than in the standard-treatment group during the post-intervention period, which may be related to the less intensive treatment.
- Kidney-Related Adverse Events: The intensive treatment group had a higher incidence of acute kidney injury or acute renal failure.
- Generalizability: While the study included a large and diverse population, results may not be generalizable to all populations.
Conclusion
The SPRINT trial’s final report strongly supports the benefits of intensive blood pressure control in reducing cardiovascular events and mortality among high-risk patients. The study found that targeting a systolic blood pressure of less than 120 mm Hg, compared to less than 140 mm Hg, resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality. These benefits were observed both during the trial intervention and in the post-intervention follow-up period. A key finding was the significantly lower incidence of myocardial infarction, heart failure, and death from cardiovascular causes in the intensive-treatment group. The results confirm that for people at increased cardiovascular risk, aiming for a lower systolic blood pressure target is beneficial. Although the intensive-treatment group experienced a higher frequency of certain adverse events such as hypotension, electrolyte abnormalities, and acute kidney injury or acute renal failure, these events were carefully monitored. The authors note that the study outcomes may be driven by differences in diuretic treatment and that the findings support lower systolic blood pressure targets for high-risk individuals. The results from this study provide robust evidence for the effectiveness of aggressive blood pressure management in preventing cardiovascular disease and improving overall survival in high-risk patients. The analysis also acknowledges that potential explanations include a lower intensity of blood pressure treatment in the intensive-treatment group and random variation due to fewer cases having occurred during the postintervention period.