IMPORTANCE The randomized Systolic Blood Pressure Intervention Trial (SPRINT) showed that lowering systolic blood pressure targets for adults with hypertension reduces cardiovascular morbidity and mortality in general. However, whether the overall benefit from intensive blood pressure control masks important heterogeneity in risk is unknown. OBJECTIVE To test the hypothesis that the overall benefit observed in SPRINT masked important heterogeneity in risk from intensive blood pressure control. DESIGN, SETTING, AND PARTICIPANTS In this exploratory, hypothesis-generating, ad hoc, secondary analysis of data obtained from 9361 participants in SPRINT, a random forest-based analysis was used to identify potential heterogeneous treatment effects using half of the trial data. Cox proportional hazards regression models were applied to test potential heterogeneous treatment effects on the remaining data. The original trial was conducted at 102 sites in the United States between November 2010 and March 2013. This analysis was conducted between November 2016 and August 2017. INTERVENTIONS Participants were assigned a systolic blood pressure target of less than 120 mm Hg (intervention treatment) or of less than 140 mm Hg (standard treatment). MAIN OUTCOMES AND MEASURES The primary composite cardiovascular outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS Of 9361 participants in SPRINT, 466 participants (5.0%) were current smokers with systolic blood pressure greater than 144 mm Hg at baseline, with 230 participants (49.4%) randomized to the training data set and 236 participants (50.6%) randomized to the testing data set; 286 participants (61.4%) were male, and the mean (SD) age was 60.7 (7.2) years. Combinations of 2 covariates (ie, baseline smoking status and systolic blood pressure) distinguished participants who were differentially affected by the intervention. In the testing data, Cox proportional hazards models for the primary outcome revealed a number needed to harm of 43.7 to cause 1 event across 3.3 years among participants who, at baseline, were current smokers with systolic blood pressure greater than 144 mm Hg (10.9%[12 of 110] of primary outcome events for intervention treatment vs 4.8%[6 of 126] for standard treatment; hazard ratio, 10.6; 95% CI, 1.3-86.1; P=.03). This subgroup was also associated with a higher likelihood to experience acute kidney injury under intensive blood pressure control (with a frequency of 10.0%[11 of 110] of acute kidney injury events for intervention treatment vs 3.2%[4 of 126] for standard treatment; hazard ratio, 9.4; 95% CI, 1.2-77.3; P=.04). CONCLUSIONS AND RELEVANCE In this secondary analysis of SPRINT data, current smokers with a baseline systolic blood pressure greater than 144 mm Hg had a higher rate of cardiovascular events in the intensive treatment group vs the standard treatment group. Further research is needed to evaluate the potential tradeoffs of intensive blood pressure control in hypertensive smokers.
