The Association of Intensive Blood Pressure Treatment and Non-Fatal Cardiovascular or Serious Adverse Events in Older Adults with Mortality: Mediation Analysis in SPRINT

Background and Aims Randomized clinical trials of hypertension treatment intensity evaluate effects on incident major adverse cardiovascular events (MACE) and serious adverse events (SAE). Occurrences after a non-fatal index event have not been rigorously evaluated. The current aim was to evaluate the association of intensive ( Methods Logistic regression and causal mediation modeling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). Results The direct effect of intensive treatment was a lowering of ACM [OR 0.75, 0.60-0.94]. The MACE-mediated effect substantially attenuated [OR 0.96, 0.92-0.99] ACM; while the SAE-mediated effect was associated with increased [OR 1.03, 1.01-1.05] ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted the SAE incidence was 3.9-fold higher than MACE incidence (13.7% vs 3.5%), and there was a total of 365 (3.9%) ACM with non-CVM 2.6-fold higher than CVM [2.81% (263/9,361) vs 1.09% (102/9,361)]. The SAE to MACE and non-CVM to CVM preponderance was across all age-groups with the ≥ 80-year age group having the highest differences. Conclusion The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when MACE-mediated and possibly harmful when SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.