Methodological Aspects of Meta-Analyses Assessing the Effect of Blood Pressure–Lowering Treatment on Clinical Outcomes

Systematic reviews and meta-analyses are often considered the highest level of evidence, with high impact on clinical practice guidelines. The methodological literature on systematic reviews and meta-analyses is extensive and covers most aspects relevant to the design and interpretation of meta-analysis findings in general. Analyzing the effect of blood pressure-lowering on clinical outcomes poses several challenges over and above what is covered in the general literature, including how to combine placebo-controlled trials, target-trials, and comparative studies depending on the research question, how to handle the potential interaction between baseline blood pressure level, common comorbidities, and the estimated treatment effect, and how to consider different magnitudes of blood pressure reduction across trials. This review aims to address the most important methodological considerations, to guide the general reader of systematic reviews and meta-analyses within our field, and to help inform the design of future studies. Furthermore, we highlight issues where published meta-analyses have applied different analytical strategies and discuss pros and cons with different strategies.