These data collectively suggest that inten- sive BP lowering increased the risk of AKI in people with moderate CKD and advanced age, but the episodes were rather infrequent, affecting less than 4% of SPRINT participants and tended to be mild and reversible (Supplementary Polypharmacy. Most participants in SPRINTwere taking 1 or 2 BP-lowering therapies before randomization. The bene ts of intensive SBP lowering are unclear among patients who require 4 or more BP-lowering medications to achieve SBP <120 mm Hg. In a post hoc analysis of the SPRINT database, the number of additional BP-lowering medications was an independent pre- dictor of poorer survival.152 However, the requirement for multiple medications to achieve SBP <120 mm Hg may re ect the patient s underlying characteristics and does not imply that intensive SBP lowering is not bene cial. Indeed, in another study using the SPRINT database and more advanced statistical tech- niques that account for confounding by indication, the addition of a new antihypertensive drug class led to signi cant reductions in SBP and major CV event rates but no difference in serious adverse events. These incremental effects appeared to be consistent regardless of the level of baseline drug use.153 Hence, at present, there is no clear evidence that people who require multiple medications to achieve an SBP of <120 mm Hg would have an unfavorable risk bene t ratio. Nonetheless, poly- pharmacy also adds to treatment burden and is often associated with reduced adherence, which may be attenuated by the use of single-pill combinations. Quality of evidence. The evidence on the effects of intensive BP lowering, namely the <120 mm Hg SBP target, on critical clinical outcomes such as CV events and all-cause mortality is considered to be moderate due to study limitations, while the effect on kidney failure is weak. 