Accumulating Evidence of Benefits From Intensive Blood Pressure Lowering
Are We There Yet?
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See related article, pp 642–653
In this issue of the journal, Verdecchia et al1 report an important analysis of the accumulation of evidence comparing more versus less intensive blood pressure (BP)–lowering strategies. Their key message is critical for guidelines and practice internationally: with the addition of SPRINT (Systolic Blood Pressure Intervention Trial),2 this set of trials now provides compelling evidence that more intensive BP-lowering reduces stroke and myocardial infarction (MI), and significant reductions are now also seen in cardiovascular death and heart failure. The authors have also assessed sequential monitoring boundaries for each outcome, making the analogy of a hypothetical Data and Safety Monitoring Board (DSMB) assessing the accumulation of evidence in the field.
Before examining the implications, it is worth reviewing the techniques and aims of the cumulative meta-analysis and trial sequential analysis methods used by Verdecchia et al.1 Cumulative meta-analysis orders trials by publication date and presents updated meta-analysis estimates with each additional trial, with the aim of establishing if and when a treatment effect reaches statistical significance. Cumulative meta-analysis has a long history of providing important insights. Most notably, a highly influential series of cumulative meta-analyses showed that traditional narrative reviews often failed to mention important advances, delayed recommending effective preventive measures, and continued to recommend some treatments long after accumulated evidence had shown them to be ineffective or harmful.3 As such the article was pivotal in the widespread adoption of systematic reviews in recent decades and indeed was one of the seminal articles in the evidence-based medicine movement. Trial sequential analyses add an important dimension and are motivated by the fact that as evidence emerges, chance extreme findings are common. It is generally not intuitive how likely, by chance alone, early data on effective treatments can appear neutral or even harmful; and …