Resistant Hypertension in Chronic Kidney Disease

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renin-angiotensin blockade, calcium channel blocker, and a thiazide or loop
diuretic. Clinical event outcome data are anticipated. However, the study excluded
those with CKD (eGFR <30/mL/min/1.73  m^2 ) perhaps due to the greater risk of
treatment-related adverse events. We have summarized unmet needs in outcomes
research in resistant hypertension in Table 5.4. Future trials in RH should address
these major unmet needs by including those with CKD, indeed the greater event
rates, and greater prevalence of RH would be expected to reduce the numbers of
participants and time needed to demonstrate clinical effectiveness in this challeng-
ing population. Widening the clinical outcomes to incorporate patient- experience
measures are also essential to understand and improve drug adherence. In 2008, the
American Heart Association Scientific Statement on resistant hypertension made a
powerful call to action noting that “the degree to which cardiovascular risk is
reduced with treatment of resistant hypertension is unknown” [ 5 ]. It is chastening
to acknowledge that several years later the question remains largely unanswered.
There is an urgent need for clinical trials using pragmatic designs that go beyond
traditional measured clinical outcomes to capture the totality of the patient

Table 5.4 Unmet needs for research in resistant hypertension with and without CKD

Improve epidemiology data by phenotyping of resistant hypertension at all stages of CKD with

greater use of ambulatory or home BP monitoring and assessment of drug adherence

Large-scale randomized outcome trials in resistant hypertension across all stages of CKD to

determine:

1. Optimum blood pressure targets

2. Preferred fourth line drug combinations through networked trials such as those pursued by the

British Hypertension Society PATHWAY project

3. The efficacy of procedures and device-based therapies.
   More epidemiology reporting the psychosocial and socioeconomic effect of resistant
   hypertension in CKD
   Integrating patient-important outcomes and patient-reported experience measures to traditional
   clinical outcomes in observational and intervention studies. Clinicians and researchers must
   acknowledge that a key factor in drug nonadherence is reduced quality of life from taking
   multiple drugs that is a competing risk to the quality of life impact of cardiovascular and renal
   events. Patients and clinicians make these tradeoffs when choosing to stop a drug or limit a dose.
   Integrating these wider measures and measures of treatment harms into informed patient
   decision aids are an essential step toward reducing apparent treatment resistance
   Work with hypertension research community to prevent exclusion of patients with CKD from
   general hypertension trials and use prespecified analyses with adequate power to describe
   treatment effects in CKD and resistant hypertension subgroups. Recent trials such as the
   Systolic Blood Pressure Intervention Trial (SPRINT, 28% eGFR 20–59 mL/min/m^2 ) are a
   positive step
   Clinical trials of hypertension in renal transplant recipients regardless of renal function and
   patients on dialysis or with eGFR <30 mL/min/m^2. They remain routinely excluded from all
   general hypertension trials as well as CKD-specific trials
   Perform pragmatic randomized registry-based clinical trials with approved drugs using
   innovative and flexible designs to permit low running costs. These would answer important
   clinical questions that are not of commercial interest at a cost that is affordable to public
   funders.

5 Resistant Hypertension and Outcomes in Patients with and Without Chronic Kidney...