Simvastatin and Diastolic Dysfunction

Effect of the Addition of Simvastatin to Enalapril in Hypertensive Individuals With Average Cholesterol Levels and Diastolic Dysfunction

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Diastolic Dysfunction
• Intervention / Treatment: Drug: Placebo; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • DF
    • Brasilia, DF, Brazil, 70000.000
      • Instituto de Cardiologia do Distrito Federal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 1 pill once a day
Experimental: Simvastatin; Simvastatin 80 mg/day	Drug: Simvastatin; 80 mg once a day; Other Names: Zocor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in E/A ratio and e' wave velocity	20 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in left atrium volume.	20 weeks
Changes in left ventricular mass.	20 weeks
Changes in e´/a´ waves ratio.	20 weeks
Changes in mitral deceleration time.	20 weeks
Changes in the ratio of mitral inflow velocity to annular relaxation velocity.	20 weeks
Changes in mitral annulus systolic velocity	20 weeks
Diastolic function reserve index measured at peak stress with dobutamine	20 weeks

Collaborators and Investigators

• Sponsor: Brasilia Heart Study Group
• Collaborators: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Fundação de Amparo a Pesquisa do Distrito Federal
• Investigators: Principal Investigator: Adenalva LS Beck, MD, InCor Heart Institute; Study Chair: Andrei C Sposito, MD, PhD, University of Brasilia Medical School, Brasilia, Brazil; Principal Investigator: Maria E Otto, MD, PhD, Instituto de Cardiologia do Distrito Federal, Brasilia, Brazil

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: February 2, 2010
• First Submitted That Met QC Criteria: February 2, 2010
• First Posted (Estimate): February 3, 2010

Study Record Updates

• Last Update Posted (Estimate): February 3, 2010
• Last Update Submitted That Met QC Criteria: February 2, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: hypertension; Statins; Echocardiography; ACE inhibitor; Diastolic dysfunction
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: Statin_DD