Box 22.1Unresolved Issues in the Management of Hypertension Requiring Further Evidence from Randomized Controlled Trials

  1. Do the use of home, ambulatory, and office blood pressure (BP) monitoring and BP variability add incremental value to routine clinic BP monitoring for optimizing hypertension management? If so, what levels of each of these measures should be used as thresholds and targets?
  2. At what BP levels (BP thresholds) should antihypertensive agents be initiated (if at all) for various subgroups of patients, including young persons (younger than age 40 years), elderly persons (older than age 65 years), persons with white-coat hypertension (high only in medical settings), and persons at relatively low CV risk? The latter subgroup has recently been investigated in the HOPE-3 trial (Lonn and others 2016).
  3. How far should BP be lowered (targets) in the general management of hypertension and in specific subgroups? The SPRINT trial (Wright and others 2015) has addressed this question in high-risk hypertensive patients, but the measurement techniques used in the trial make direct translation of results into clinical practice difficult. Meanwhile, meta-analyses of this question have generated conflicting results (Brunström and Carlberg 2016; Ettehad and others 2016; Xie and others 2016).
  4. What are the best two-, three-, and four-drug combinations for optimizing BP management for particular ethnic groups? The PATHWAY-2 study (Williams and others 2015) has provided robust evidence that spironolactone is the best fourth-line agent for resistant hypertension (after a renin-angiotensin-system blocker, a calcium channel blocker, and a diuretic have been shown to be inadequate). No data are available to support the best combinations of antihypertensives in each of the major ethnic groups.
  5. Beyond the use of spironolactone as a fourth-line agent—for which an alpha blocker and a beta blocker are recommended add-on drugs (NICE 2011)—various devices and interventions, including renal denervation, are undergoing investigation, but no such interventions are currently established.
  6. How is BP best measured for patients with atrial fibrillation?
  7. How is CV risk best assessed for patients with elevated BP?
  8. Can target organ damage be used reliably as a surrogate outcome in trials of hypertension management?
  9. Is it possible or reasonable to evaluate lifestyle interventions to lower BP and thereby reduce major adverse CV events in randomized controlled trials?

Based on a summary of recent U.K. and European guidelines (Mancia and others 2013; NICE 2011).

From: Chapter 22, Management of Hypertension and Dyslipidemia for Primary Prevention of Cardiovascular Disease

Cover of Cardiovascular, Respiratory, and Related Disorders
Cardiovascular, Respiratory, and Related Disorders. 3rd edition.
Prabhakaran D, Anand S, Gaziano TA, et al., editors.
© 2017 International Bank for Reconstruction and Development / The World Bank.

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