Refractory High Blood Pressure

Refractory hypertension

Refractory hypertension (or intractable hypertension) means that after the application of sufficient and reasonable combination of three antihypertensive drugs (including Diuretic), the blood pressure is still above the target level, or at least four antihypertensive drugs are required to make the blood pressure reach the standard. After the treatment of antihypertensive drugs, the blood pressure of general hypertensive patients can be controlled at a satisfactory level, and 15%~20% of hypertensive patients are intractable hypertension.

The European guidelines speculate that in the population using two antihypertensive drugs, 15% to 30% of patients have blood pressure levels<140/90 mm Hg; However, others require multiple antihypertensive drugs with different mechanisms of action to achieve blood pressure standards. For hypertensive patients who are difficult to treat, it is necessary to identify refractory hypertension and identify white coat hypertension and hypertensive patients with poor adherence to antihypertensive drugs.

Hanus et al. investigated 7306 male and 5069 female hypertensive patients, and the results showed that women with refractory hypertension were older than men. In a multivariate regression model, pulse pressure widening, metabolic syndrome, cardiovascular disease, and glomerular filtration rate<60 ml/(rain · 1.73 m2) were associated with the onset of refractory hypertension.

In the ROVIGO study, 580 hypertensive patients aged>65 years were selected. The results showed that the incidence rate of refractory hypertension was 5.7%, 8.3% for men and 3.0% for women. Chronic. Kidney disease (OR=3.89) and Hyperuricemia (OR-3.11) can predict the occurrence of refractory hypertension. Schiefer et al. explored the impact of postural dependent renal perfusion disorder on the pathogenesis in patients with refractory hypertension. The results show that position dependent renal perfusion should be considered in refractory hypertension, and although renal morphology and imaging are normal, renal function has changed.

Martin Lorenzo et al. observed the metabolic changes in the urine of patients with refractory hypertension, and assessed the potential ability of metabolites to predict the treatment response of patients to Spironolactone. The results showed that hypertension can lead to sustained activation of the citric acid cycle and dysregulation of reactive oxygen species homeostasis, manifested as changes in a series of metabolic product levels. These metabolites can help predict the response of patients to Spironolactone treatment, and optimize the control rate when Spironolactone is used to treat patients with refractory hypertension.

In January 2016, the French Society of Hypertension released the "Expert Consensus on the Management of Refractory Hypertension", which defined refractory hypertension: despite treatment (including lifestyle and diet intervention, and the current use of the best dosage of triple antihypertensive drugs, including Thiazide, for at least 4 weeks), blood pressure has not been controlled, that is, blood pressure in the consulting room ≥ 140/90 mmHg (for people younger than 80 years) or systolic pressure ≥ 150 mm Hg (for people older than 80 years), And it is determined through extracurricular blood pressure measurement (home blood pressure) or dynamic blood pressure monitoring. It is recommended to use questionnaires, urine drug analysis, and/or counting pills to evaluate patient compliance. Patient information, treatment education, and home self-monitoring of blood pressure may help improve blood pressure control. The factors that may affect treatment resistance (excessive intake of salt, alcohol, depression, Drug interaction) and the drugs and substances that cause blood pressure rise should be screened.

Compliance with medication for hypertension is crucial for the effectiveness of antihypertensive treatment, but it is often overlooked in hypertension management. Because the current methods for evaluating drug compliance are unreliable and their clinical application is limited. Existing evidence suggests that a significant proportion of patients with refractory hypertension have poor drug adherence, and poor adherence to antihypertensive drugs can offset the benefits that antihypertensive drugs bring to patients with refractory hypertension. In addition, poor drug adherence in patients with refractory hypertension is also a serious health and economic issue (number of visits, diagnostic procedures, prescription drugs).

Poor drug adherence can increase the incidence of comorbidities and mortality in patients with refractory hypertension. Poor compliance can occur in some patients and is related to some treatments; There are various direct and indirect methods for evaluating drug compliance, among which therapeutic drug monitoring and monitoring of drug concentration in body fluids (including urine, blood, etc.) are effective methods for evaluating drug compliance. By reducing the number of visits and determining that invasive examinations are not required, therapeutic drug monitoring has reduced health costs. Therapeutic drug monitoring is a new and important method for identifying refractory hypertension.

PATHWAY 2 study analyzed 314 patients with refractory hypertension (systolic blood pressure of non diabetes patients>140 mm Hg, systolic blood pressure of diabetes patients>135 mm Hg). On the basis of basic antihypertensive treatment, they received Spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin (4-8 rag) or placebo in sequence. The results showed that compared with the placebo group, the family measured systolic blood pressure of patients in the Spironolactone group further decreased by 8.70 mm Hg; Compared with the bisoprolol/doxazosin group, the Spironolactone group further reduced the home measured systolic blood pressure by 4.26 mm Hg.

It is the first time to confirm the Absolute advantage of Spironolactone (25-50 mg/d) over other drugs in the treatment of refractory hypertension. The control rate for refractory hypertension is almost 60%, significantly higher than other groups. A study analyzed the drug treatment of refractory hypertension in the United States. The study selected 261652 hypertensive patients aged 18-65 who used four antihypertensive drugs, including 41652 patients with refractory hypertension. The analysis results show that the use of Thiazide increased by 2.6% and the use of Spironolactone only increased by 2.9% in the treatment of refractory hypertension drugs in the United States from 2008 to 2014. The results of this study suggest that although there is a lot of clinical evidence, the use rate of Spironolactone and Thiazide is still low.

The sYMPATHY trial was conducted from May 2013 to January 2026 in patients with refractory hypertension. After taking three or more antihypertensive drugs, the average daytime systolic blood pressure was 135 mm Hg. Subjects received catheter based renal Sympathetic nervous system denervation plus conventional treatment or simple conventional treatment. The primary endpoint was diurnal systolic blood pressure after 6 months, while the secondary endpoint included changes in diagnostic room systolic blood pressure. The results showed that renal Sympathetic nervous system denervation reduced the systolic blood pressure of the subjects, but the effect was not obvious, because 80% of the subjects had poor or incomplete compliance with the treatment.