Nijmegen Antihypertensive Management Improvement Study
Condition: Primary Hypertension
MeSH terms: Hypertension; Essential Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      High blood pressure is an important risk factor for diseases of heart and blood vessels like
      myocardial infarction and stroke. Many patients are not treated to target blood pressures,
      even though good blood pressure lowering drugs are available. Not all blood pressure drugs
      are equally effective in individual patients.

      We hypothesize that individual patient characteristics can predict the best response on
      different blood pressure lowering drugs. In this study we will investigate whether a set of
      patient characteristics (anthropometric and laboratory) obtained before treatment may predict
      the blood pressure lowering response to representatives of two groups of drugs: those that
      inhibit renin-angiotensin system activity and those that decrease blood volume.
    

Detailed description: 
      Population-wide elimination of hypertension would reduce the incidence of all stroke, MI and
      heart failure with 30 to 50% and contribute to a reduction of between 25 to 50% of the total
      mortality related to these cardiovascular conditions. However, despite increasing numbers of
      antihypertensive medication prescriptions, hypertension control rates are still insufficient.

      The current study will focus on improving the success rate of the initial treatment of
      hypertension. The individual response to antihypertensive drugs varies between individuals:
      many patients responding well to one drug respond poorly to another. We hypothesize this
      difference in response to depend on the presence of certain characteristics of patients, like
      waist circumference, age and gender.

      The major objective of our study will be to identify patient characteristics that predict the
      efficacy of different classes of antihypertensive drugs. Despite pleas in international
      publications to tailor antihypertensive treatment on individual basis, until now patient
      characteristics are not taken into account in the medical treatment of hypertension. We will
      address our study objective by the use of a PRospective, Open label (medication not blind),
      Blinded End-point crossover design (PROBE) in which 100 general practice based, newly
      diagnosed hypertensive patients, aged 18 - 65 years will be included to be treated with a
      diuretic and an angiotensin receptor blocker (ARB). Each patient will be treated with
      standard doses of both medications consecutively. Treatment duration for each medication will
      be four weeks, with a four weeks washout period in between. The choice for a diuretic versus
      an ARB is based on the substantial difference in working mechanism representing the two major
      determinants of blood pressure: effect on intravascular volume (diuretic) or vascular tone
      (ARB). Blood pressures will be assessed with both 24 hour-monitoring and practice based
      standardized measurements.

      Twenty-three different patient characteristics will be studied and were selected based on
      review of literature and pathophysiologic theory. These characteristics will be (1) simple
      anthropometric measures like body mass index and fat distribution, (2) demographic
      characteristics, such as gender or ethnicity or (3) disease characteristics such as baseline
      diastolic and systolic blood pressure, co-morbidity and blood plasma levels of easily
      measured bioactive compounds, like renin and B-type natriuretic peptide.

      The primary outcome measure will be the difference in blood pressure response between both
      study drugs; secondary outcome measures will be the difference in the number of patients
      achieving target blood pressure and the number of adverse drug events.

      We expect to find three to six significant patient characteristics that predict response to
      antihypertensive medication in terms of blood pressure reduction.

      If our study indeed identifies relevant patient characteristics GPs will be able to initiate
      antihypertensive medical treatment more efficiently. We expect this will result in increased
      initial therapeutic success and reduction of the number of antihypertensive drugs needed. As
      a consequence we expect compliance and hypertension control rates to increase. These
      expectations will need to be confirmed in a general practice-based follow-up study on
      implementation in daily practice of the use of patient characteristics with compliance and
      hypertension control rates as outcome measures.
    

Intervention name(s): hydrochlorothiazide; valsartan, 80 mg once-a-day
Intervention type(s): Drug; Drug
Intervention description(s): 12.5 mg once-a-day; 80 mg once-a-day
Intervention MeSH terms: Valsartan; Hydrochlorothiazide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: hypertension; diuretic; angiotensin receptor blockers; prediction