Abstract
Despite the availability of anti-hypertensive medications with increasing efficacy up to 50% of hypertensive patients have blood pressure levels (BP) not at the goals set by international societies. Some of these patients are either not optimally treated or are non-adherent to the prescribed drugs. However, a proportion, despite adequate treatment, have resistant hypertension (RH), which represents an important problem in that it is associated to an excess risk of cardiovascular events. Notwithstanding a complex pathogenesis, an abundance of data suggests a key contribution for the mineralocorticoid receptor (MR) in RH, thus fostering a potential role for its antagonists in RH. Based on these premises randomized clinical trials aimed at testing the efficacy of MR antagonists (MRAs) in RH patients have been completed. Overall, they demonstrated the efficacy of MRAs in reducing BP and surrogate markers of target organ damage, such as microalbuminuria, either compared to placebo or to other drugs. In summary, owing to the key role of the MR in the pathogenesis of RH and on the proven efficacy of MRAs we advocate their inclusion as an essential component of therapy in patients with presumed RH. Conversely, we propose that RH should be diagnosed only in patients whose BP values show to be resistant to an up-titrated dose of these drugs.
Highlights
Reviewed by: Piyali Chatterjee, Baylor Scott and White Health, USA Cristiana Catena, University of Udine, Italy Jane A
RESISTANT HYPERTENSION: WANDERING DEFINITIONS ARE NOT HELPFUL The development of novel anti-hypertensive medications with increasing efficacy and decreasing adverse effects might generate the deceitful impression that decreasing patients’ blood pressure (BP) at the goals set by international societies is no longer an issue
The American Heart Association (AHA) definition is even less restrictive in that it defines as resistant hypertension (RH) patients those on more than three medications, even though their blood pressure levels (BP) is at target [13]
Summary
Systolic and diastolic blood pressure values above 140 and 90 mmHg, respectively Therapeutic strategy including lifestyle measures Drug therapy including a diuretic and two other antihypertensive drugs belonging to different classes at adequate doses. Messerli et al proposed an even more restrictive definition: a systolic BP of 160 mmHg or higher despite treatment with a full dose of a renin–angiotensin–aldosterone system (RAAS) blocker (either an ACE-I, an ARB, or a renin inhibitor), a CCB (either dihydropyridine or non-dihydropyridine), a diuretic (preferentially chlorthalidone), and, if tolerated, a mineralocorticoid receptor (MR) antagonist (MRA) (spironolactone or eplerenone) [23] Such more strict criteria to define RH could be useful but carry some limitations: patients not having BP at goal despite being treated with more than three drugs, but with intolerance or contraindication to a class of drugs, such as, for example, a RAAS blocker in subjects with bilateral renal artery stenosis, or a CCB in those with low ejection fraction heart failure, would not meet the definition for RH. While studies comparing resistant and non-resistant hypertensives consistently showed a higher risk in former, up to 50% (hazard ratio 1.47, 95% confidence interval 1.33–1.62) of cardiovascular events and renal events [5, 32, 38], the estimates of this excess risk are imprecisely
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