A workgroup of 10 stakeholders identified the following seven research areas as the highest priority for future research for the comparative effectiveness of ACEIs, ARBs, or DRIs in patients with hypertension.

  1. What is the comparative effectiveness of these medications on cardiovascular and cerebrovascular events measured over several years?
    1. Recommended study design: if able to combine with chronic conditions other than hypertension, then a systematic review with broader inclusion criteria could provide additional information not included in the CER, which was restricted to patients with hypertension. If not, then large long-term clinical trial or observational study would be preferable
  2. What is the impact of comorbidities (such as ischemic heart disease, CHF, diabetes, peripheral arterial disease, or chronic kidney disease) on ACEI/ARB/DRI effectiveness or harms in patients with hypertension?
    1. Recommended study design: if patient-level data are available from relevant trials, then a patient-level meta-analysis may be the most efficient approach.
  3. What is the impact of demographic differences (such as age, race, or sex) on the effectiveness or harms of ACEI/ARB/DRIs in patients with hypertension?
    1. Recommended study design: if patient-level data are available from relevant trials, then a patient-level meta-analysis is most appropriate.
  4. Do the results differ in practical clinical trials or other or other external validity-oriented studies that compare these medications in practice settings that better represent real-world practice?
    1. Recommended study designs: either a large clinical trial with broader inclusion criteria to maximize generalizability, or an observational study of patients in typical community practice.
  5. What is the impact of ACEI/ARB/DRI on incidence of new cardiovascular or metabolic diagnoses such as diabetes, atrial fibrillation, or CHF with or without preserved LV function?
    1. Recommended study design: if patients can be combined across clinical conditions (i.e., not exclusively hypertension), then a systematic review of existing studies is most appropriate.
  6. What is the impact of ACEI/ARB/DRI on patient health status including quality of life and functional capacity?
    1. Recommended study design: randomized controlled trials (RCTs) with the inclusion of validated quality of life measures as an outcome.
  7. Are there important differences in medication adherence and persistence with drug therapy across the different classes of drug?
    1. Recommended study design: new observational studies with a focus on the longitudinal measurement of adherence and persistence.