72
more commonly of black ethnicity (43% vs 31%), higher body mass index (31 vs
30), more frequent ECG criteria for left ventricular hypertrophy (21% vs 15%), and
lower eGFR (72.5 vs 75.4 mL/min/1.73 m^2 ). The multivariable-adjusted hazard
ratios comparing participants with versus without aTRH were reported for several
outcomes: Coronary heart disease (1.4; 95% CI, 1.2–1.8), stroke (1.6; 95% CI, 1.2–
2.1), all-cause mortality (1.3; 95% CI, 1.1–1.5), heart failure (1.9; 95% CI, 1.5–2.3),
and end-stage renal disease (2.0; 95% CI, 1.1–3.4). These results demonstrate that
aTRH increases the risk for cardiovascular disease and end-stage renal disease.
Studies are needed to identify approaches to prevent aTRH and reduce risk for
adverse outcomes among individuals with aTRH.
Conclusions
Among patients newly starting treatment for hypertension, 1 in 50 will go on to
develop resistant hypertension within 1.5 years. In addition, one in six patients tak-
ing three hypertension medications will continue to meet criteria for resistant
hypertension over follow-up. Observational studies of RH have reported higher
rates of vascular disease and end-organ damage at baseline. Those with RH have a
greater risk for cardiovascular events, renal events, and mortality under follow-up
even when restricted to those with no prior events at baseline. The prevalence of
RH has a stepwise increase with declining stages of CKD and is typically two to
three times greater than a matched non-CKD group. Study comparisons are ham-
pered by variation in the definitions of RH used in the studies and the extent to
which pseudoresistance has been excluded. For example, many studies use the
term RH without reporting whether there was optimal dosing, exclusion of nonad-
herence or use of diuretics. The preferred use of the term apparent resistance to
emphasize that pseudoresistance has not been excluded has been inconsistent.
Normotension, responder hypertension, nonresistant hypertension, and controlled
RH have all been used to describe the same groups. Despite the presence of CKD
being the greatest risk factor for developing RH, there is a particular lack of robust
evidence to guide the clinical care of patients with RH in the setting of CKD. It is
disappointing that both past and recent well-designed trials of hypertension and
RH have routinely excluded those with CKD, despite this group having the greatest
potential benefit. For example, the recently reported Prevention And Treatment of
resistant Hypertension With Algorithm based therapY (PATHWAY-2) trial is the
first randomized controlled trial to directly compare spironolactone with other
active BP-lowering treatments (alpha-blockers and beta-blockers) in 335 patients
with well-characterized RH [ 28 ]. The trial showed that RH could be controlled in
the majority of patients and that spironolactone was a superior fourth line treat-
ment to other drug classes in terms of home BP reduction. These early results
are important as they suggest that in some participants, true RH is driven by sub-
clinical hyperaldosteronism or fluid retention despite optimal dosing of
A. Odudu et al.