Optimal Medical Treatment of Difficult-to-treat Hypertension

Inclusion Criteria:

• documented history of HT
• HT treated for at least six months,
• office BP ≥ 130 and / or ≥80 mm Hg (average seated BP at Visit 1)
• use of 3 or more antihypertensive drugs, including an ACEi/ARB and athiazide/thiazide-like diuretic or loop diuretic (single drugs or double SPCs)
• stable antihypertensive treatment regimen - no changes in antihypertensive treatmentstrategy at least for 4 weeks
• able and willing to comply with all study procedures and able to attend one of thestudy centers

Exclusion Criteria:

• inability to give informed consent
• SBP ≥180 mm Hg and/or DBP ≥110 mm Hg and/or DBP <60 mm Hg
• BMI ≥40 kg/m2
• eGFR of <45 mL/min/1.73 m2
• potassium serum concentration > 4.8 mmol/L or < 3.5 mmol/L
• persistent hyponatremia or history of hyponatremia related to TD/TLD treatment (sodiumconcentration <135 mmol/L)
• secondary hypertension (not including sleep apnea)
• chronic oral glucocorticoid therapy
• myocardial infarction or cerebrovascular event (e.g. stroke, transient ischemic event,cerebrovascular accident) in the year prior to study inclusion
• heart failure requiring treatment with diuretic or aldosterone antagonists
• cardiomyopathy exluding LVH related to HT
• severe valvular disease
• ascending aortic aneurysm ≥5 cm
• prescribed to any standard antihypertensive of cardiovascular medication (e.g. betablockers) for other chronic conditions (e.g. chronic coronary syndromes, arytmia) suchthat discontinuation might pose serious risk to health
• primary pulmonary hypertension
• decompensated hyperthyroidism or hypothyroidism
• severe liver dysfunction (alanine aminotransferase and/or asparagine aminotransferaseactivity ≥3 times the upper limit of normal value),
• documented contraindication or allergy to studied drugs
• limited life expectancy of < 1 year at the discretion of the Investigator
• any known, unresolved history of drug use or alcohol dependency, lacks the ability tocomprehend or follow instructions, or for any reason in the opinion of theinvestigator, would be unlikely or unable to comply with study protocol requirements
• all women of child bearing potential; women of child bearing potential can be includedin the study ONLY after providing documentation of effective contraception (intrauterine device);
• concurrent enrollment in any other investigational drug or device trial
• anticipated change of medical status during the trial (e.g., surgical interventionrequiring >2 weeks convalescence)
• current therapy for cancer