The research of clinical effectiveness assessment is to explore the causal relationship between treatment and outcome.Accordingly, based on the effectiveness of tan-yu treatment, the research takes the Resistant Hypertension (RH) as example to study the causal inference methods under real world.

Background: Syndrome differentiation is one of the substantial characteristics in Traditional Chinese Medicine (TCM) but is still lack of scientific evidence.The inference methods of causal relationship between treatment and clinial effect under real-word study may help.

Objectives: This study aims to assess the efficacy of Phlegm and Stasis Syndrome differentiation method in treating resistant hypertension and explore causal inference in the real-world study.

Research design and methods: It is a multi-center,prospective,two-arm,cohort study including 200 patients with resistant hypertension (doctors' diagnosis based on the American Heart Association criteria 2008).Essential hypertension subjects,aged 18-70 years,blood pressure >140/90mmHg even used to be on 3 or more medications for a month and diagnosed as Phlegm and Stasis Syndrome will be included.Thiazide diuretics and/or two more antihypertensive agents for 8 weeks, Chinese herbs (for synchronic treating phlegm and blood stasis) and nonpharmacological recommendations were initiated in the observational group and the control group received the same interventions without Chinese herbs.

Outcome measures: The primary outcomes will be Systolic (SBP) and Diastolic (DBP) blood pressure reductions and changes in symptoms and signs.Cardiac event and death incident will be the secondary outcomes.Possible side effects and adverse reactions arising from the treatment like diarrhea will be recorded.

Discussion: This is a rigorous methodology pilot study and 200 patients are enough to calculate sample size in later formal trial.

Inclusion Criteria:

• Essential hypertension subjects, aged 18-70 years, blood pressure > 140/90 mm Hg even used to be on 3 or more medications for a month and diagnosed as Phlegm and Stasis Syndrome will be included.

Exclusion Criteria:

• Patients will be excluded for the following conditions: with secondary resistant hypertension because of other disease like renal disease or pheochromocytoma; included in other clinical trial in one month; pregnant or breast-feed or preparing for pregnancy female; combined with disease like stroke, coronary atherosclerotic heart disease, diabetes, chronic renal failure or mental disease.