Clinical trial NCT01061450: Simvastatin and Diastolic Dysfunction
Official title: Effect of the Addition of Simvastatin to Enalapril in Hypertensive Individuals With Average Cholesterol Levels and Diastolic Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diastolic Dysfunction
Hypertension
Keywords: Diastolic dysfunction
hypertension
Statins
ACE inhibitor
Echocardiography
Lead sponsor: Brasilia Heart Study Group
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo a Pesquisa do Distrito Federal
name: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
First posted: 2010-02-03
Enrollment: 55
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Diastolic dysfunction (DD) is an increasingly frequent condition in hypertensive individuals whose treatment remains unclear. Its presence is related to higher morbidity and mortality independent of blood pressure levels. The aim of this study is to investigate the additive effect of simvastatin on enalapril on DD in hypertensive patients with average cholesterol levels.

For this aim, hypertensive patients with DD and LDL-cholesterol \<160 mg/dL will undergo a run-in phase to achieve a systolic blood pressure (SBP) \<135 mmHg and diastolic blood pressure (DBP) \<85 mmHg with enalapril. Hydrochlorothiazide could be added when need to achieve SBP or DBP control. Four weeks after reaching the optimum anti-hypertensive regimen patients will be randomized to receive 80 mg simvastatin or placebo for a period of 20 weeks. Echocardiograms will be performed before and after treatment with measurement of left atrial volume, conventional and tissue Doppler velocities in early diastole and late diastole. The evaluation of these will allow to identify changes of DD severity after treatment.


Eligibility criteria: Inclusion Criteria:

* men or postmenopausal women aged between 40 and 65 years old
* normal fasting blood glucose (\<100 mg/dL) and glucose tolerance test (\<140 mg/dL)
* waist circumference \< 102 cm (men) or \< 88cm (women)
* triglycerides \<150 mg/dL, LDL cholesterol ≤ 160 mg/dl
* creatinine \<1.2 mg/dL, sinus rhythm
* the presence of grade 1 or 2 of DD with an ejection fraction of left ventricle \> 55%
* absence of myocardial ischemia during dobutamine stress echocardiography

Exclusion Criteria:

* thyroid dysfunction
* acute or chronic liver disease
* regular use of 3 or more antihypertensive drugs
* secondary hypertension
* symptoms or history of atherosclerotic disease
* valvular dysfunction
* LVH 14 and use of statins in the last 6 months

Primary outcomes:
measure: Changes in E/A ratio and e' wave velocity
timeFrame: 20 weeks
Secondary outcomes:
measure: Changes in left atrium volume.
timeFrame: 20 weeks
measure: Changes in left ventricular mass.
timeFrame: 20 weeks
measure: Changes in e´/a´ waves ratio.
timeFrame: 20 weeks
measure: Changes in mitral deceleration time.
timeFrame: 20 weeks
measure: Changes in the ratio of mitral inflow velocity to annular relaxation velocity.
timeFrame: 20 weeks
measure: Changes in mitral annulus systolic velocity
timeFrame: 20 weeks
measure: Diastolic function reserve index measured at peak stress with dobutamine
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Brasilia
country: Brazil
facility: Instituto de Cardiologia do Distrito Federal
state: DF
Study officials:
affiliation: InCor Heart Institute
name: Adenalva LS Beck, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Brasilia Medical School, Brasilia, Brazil
name: Andrei C Sposito, MD, PhD
role: STUDY_CHAIR
affiliation: Instituto de Cardiologia do Distrito Federal, Brasilia, Brazil
name: Maria E Otto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beck AL, Otto ME, D'Avila LB, Netto FM, Armendaris MK, Sposito AC. Diastolic function parameters are improved by the addition of simvastatin to enalapril-based treatment in hypertensive individuals. Atherosclerosis. 2012 Jun;222(2):444-8. doi: 10.1016/j.atherosclerosis.2012.03.030. Epub 2012 Apr 3.