Heart failure events in a clinical trial of arterial hypertension. The acquittal of the SPRINT trial

Abstract

Abstract Introduction The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized trial showing that intensive lowering of systolic blood pressure (BP), as compared to standard treatment (i.e. <120 vs <140 mm Hg) was associated with a reduced risk (HR 0.75 [95% CI 0.64–0.79], p<0.001) for the primary composite outcome (CE), defined as myocardial infarction, an acute coronary syndrome other than myocardial infarction, stroke, acute exacerbation of heart failure and cardiovascular death. primary outcome event in subjects at high cardiovascular risk. However, the primary endpoint events in the intensive treatment arm were only 76 fewer than in the standard treatment arm (243 vs 319 events), and he reduction in heart failure events was responsible for half of the effect (62 vs 100 events, i.e. 38 events fewer). Thus, several experts in hypertension argued that these results were mainly driven by a reduction of heart failure events, and questioned the main conclusion of the study. Aim To assess the effect of SPRINT intervention on a redefined CE: the primary SPRINT endpoint with HF events excluded. Material and methods We used limited SPRINT data, available from the NHLBI Biologic Specimen and Data Repository to assess the impact of BP intervention in SPRINT on a redefined CE excluding HF events. The Chi-square test, Cox proportional model and survival analysis were applied. Results Among 9361 SPRINT participants (mean age 67.9±9.5 years, 35.6% female, 20% with previous cardiovascular disease), there was 461 CE events. There were fewer CE events in the intensive treatment arm than in the standard treatment arm (204 [4.4%] vs 257 [5.5%], p=0.0117, respectively). Intensive systolic BP lowering was associated with lower risk for CE than standard treatment (HR 0.79 [95% CI 0.66–0.95], p=0.0115). Kaplan-Meier curves show that intensive treatment was associated with better outcome (Figure 1). Analyses in subgroups (age >75 vs <75 years, female vs male, black vs non-black, prior cardiovascular disease vs no cardiovascular disease, prior chronic kidney disease vs no chronic kidney disease) showed no difference in benefit of intensive treatment (p for interaction >0.05 in all subgroup). Conclusion The reduction in cardiovascular events by intensive BP lowering in SPRINT was not explained by a difference in heart failure events. This supports the concept that more intensive BP reduction may provide benefit in reducing cardiovascular event risk. Figure 1. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None