Abstract
IMPORTANCE The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure control reduced cardiovascular morbidity and mortality. However, the legacy effect of intensive treatment is unknown. OBJECTIVE To evaluate the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause mortality approximately 4.5 years after the trial ended. DESIGN, SETTING, AND PARTICIPANTS In this secondary analysis of a multicenter randomized clinical trial, randomization began on November 8, 2010, the trial intervention ended on August 20, 2015, and trial close-out visits occurred through July 2016. Patients 50 years and older with hypertension and increased cardiovascular risk but without diabetes or history of stroke were included from 102 clinic sites in the US and Puerto Rico. Analyses were conducted between October 2021 and February 2022. INTERVENTIONS Randomization to systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group; n = 4678) vs less than 140 mm Hg (standard treatment group; n = 4683). MAIN OUTCOMES AND MEASURES Extended observational follow-up for mortality via the US National Death Index from 2016 through 2020. In a subset of 2944 trial participants, outpatient SBP from electronic health records during and after the trial were examined. RESULTS Among 9361 randomized participants, the mean (SD) age was 67.9 (9.4) years, and 3332 (35.6%) were women. Over a median (IQR) intervention period of 3.3 (2.9-3.9) years, intensive treatment was beneficial for both cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01). However, at the median (IQR) total follow-up of 8.8 (8.3-9.3) years, there was no longer evidence of benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23). In a subgroup of participants, the estimated mean outpatient SBP among participants randomized to intensive treatment increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years following randomization. CONCLUSIONS AND RELEVANCE The beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial. Given increasing outpatient SBP levels in participants randomized to intensive treatment following the trial, these results highlight the importance of consistent long-term management of hypertension. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01206062
Generated Summary
This is a secondary analysis of a multicenter randomized clinical trial (SPRINT) that investigated the long-term effects of intensive blood pressure control on cardiovascular and all-cause mortality. The study followed participants for approximately 4.5 years after the trial ended, with analyses conducted between October 2021 and February 2022. The primary objective was to evaluate the legacy effect of intensive treatment. Participants were randomized to either a systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group) or less than 140 mm Hg (standard treatment group). Data was collected through the US National Death Index, and an ancillary study examined outpatient SBP from electronic health records. The aim was to assess the impact of intensive blood pressure control on mortality outcomes post-intervention.
Key Findings & Statistics
- The study included 9361 randomized participants with a mean age of 67.9 (9.4) years, of whom 3332 (35.6%) were women.
- The median (IQR) intervention period was 3.3 (2.9-3.9) years.
- During the trial phase, intensive treatment was associated with a reduced risk of cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01).
- However, at a median (IQR) total follow-up of 8.8 (8.3-9.3) years, the benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23) was no longer evident.
- In a subgroup of participants, the estimated mean outpatient SBP in the intensive treatment group increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years.
- The study found that 248 and 273 CVD deaths occurred among participants randomized to intensive and standard treatment, respectively.
- The HR for CVD mortality among participants randomized to intensive vs standard treatment was 0.66 (95% CI, 0.49-0.89) during the trial phase and 1.02 (95% CI, 0.84-1.24) during the observational phase.
- The total median (IQR) follow-up time was 8.8 (8.3-9.3) years.
- A total of 818 and 826 deaths occurred among participants randomized to intensive and standard treatment, respectively.
- The HR for all-cause mortality comparing intensive with standard treatment was 0.83 (95% CI, 0.68-1.01) during the trial phase, and 1.08 (95% CI, 0.94-1.23) during the observational phase.
- During the trial phase, the incidence of CVD deaths per 1000 person-years was 12.5 in the intensive treatment group and 15.1 in the standard treatment group.
- During the observational phase, the incidence of CVD deaths per 1000 person-years was 31.9 in the intensive treatment group and 29.6 in the standard treatment group.
- In the trial phase, the incidence of all-cause deaths per 1000 person-years was 12.5 in the intensive treatment group and 15.1 in the standard treatment group.
- In the observational phase, the incidence of all-cause deaths per 1000 person-years was 31.9 in the intensive treatment group and 29.6 in the standard treatment group.
- At 5 years following randomization, the estimated mean SBP was 132.8 mm Hg (95% CI, 132.0-133.7) in the intensive treatment group and 138.8 mm Hg (95% CI, 137.9-139.6) in the standard treatment group.
- At 10 years following randomization, the estimated mean SBP was 140.4 mm Hg (95% CI, 137.8-143.0) in the intensive treatment group and 140.2 mm Hg (95% CI, 137.7-142.6) in the standard treatment group.
Other Important Findings
- The beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial.
- The study highlights the importance of consistent long-term management of hypertension.
- Subgroup analyses did not show any evidence of heterogeneity for any subgroup during either phase of the trial follow-up.
Limitations Noted in the Document
- The study’s reliance on high-quality NDI matches for mortality ascertainment has limitations, potentially leading to misclassification.
- The use of NDI diagnosis codes for defining CVD mortality is subject to misclassification.
- Information on nonfatal cardiovascular events was not available during the observational phase.
- Data on SBP control after the trial were limited to routine outpatient SBP values in a subgroup, which has poor concordance with standardized BP measurement processes.
Conclusion
The findings of this study suggest that the benefits of intensive blood pressure control on mortality do not necessarily extend beyond the period of active intervention. The diminishing effect of intensive treatment on cardiovascular and all-cause mortality highlights the need for sustained BP control. The study underscores the importance of long-term management strategies to improve BP control and reduce cardiovascular disease risk. The study points out the challenge of maintaining intensive BP control in real-world settings, even in individuals who initially achieved it during the trial. Key to these findings is the fact that SBP levels increased after the active intervention ended. This emphasizes the need for sustainable strategies and consistent management to maintain the benefits observed during the trial. Further research is needed to evaluate strategies for consistent BP control in clinical settings, including those outlined in the 2020 US Surgeon General’s call to action, to reduce the burden of CVD. The study’s results also suggest that implementing comprehensive strategies for improved BP control, similar to those in the trial setting, may be essential for achieving lasting reductions in cardiovascular mortality. The findings emphasize that maintaining long-term cardiovascular health requires continuous and consistent management of blood pressure. Given increasing SBP levels in the intensive treatment group post-trial, the results underscore the necessity of consistent long-term management of hypertension to sustain the benefits observed during the intensive treatment period.