Simvastatin and Diastolic Dysfunction

• ClinicalTrials.gov Identifier: NCT01061450
• Recruitment Status: Completed
• First Posted: February 3, 2010
• Last Update Posted: February 3, 2010
• Sponsor: Brasilia Heart Study Group
• Collaborators: Fundação de Amparo a Pesquisa do Distrito Federal; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
• Information provided by: Brasilia Heart Study Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Diastolic Dysfunction; Hypertension	Drug: Simvastatin; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of the Addition of Simvastatin to Enalapril in Hypertensive Individuals With Average Cholesterol Levels and Diastolic Dysfunction
• Study Start Date: November 2006
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: August 2009

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo	Drug: Placebo; 1 pill once a day
Experimental: Simvastatin; Simvastatin 80 mg/day	Drug: Simvastatin; 80 mg once a day; Other Name: Zocor

Outcome Measures

Primary Outcome Measures :

1. Changes in E/A ratio and e' wave velocity [ Time Frame: 20 weeks ]

Secondary Outcome Measures :

1. Changes in left atrium volume. [ Time Frame: 20 weeks ]
2. Changes in left ventricular mass. [ Time Frame: 20 weeks ]
3. Changes in e´/a´ waves ratio. [ Time Frame: 20 weeks ]
4. Changes in mitral deceleration time. [ Time Frame: 20 weeks ]
5. Changes in the ratio of mitral inflow velocity to annular relaxation velocity. [ Time Frame: 20 weeks ]
6. Changes in mitral annulus systolic velocity [ Time Frame: 20 weeks ]
7. Diastolic function reserve index measured at peak stress with dobutamine [ Time Frame: 20 weeks ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

Brazil

Instituto de Cardiologia do Distrito Federal

Brasilia, DF, Brazil, 70000.000

Sponsors and Collaborators

Brasilia Heart Study Group

Fundação de Amparo a Pesquisa do Distrito Federal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Andrei C Sposito, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
• ClinicalTrials.gov Identifier: NCT01061450
• Other Study ID Numbers: Statin_DD
• First Posted: February 3, 2010
• Last Update Posted: February 3, 2010
• Last Verified: February 2010

Keywords provided by Brasilia Heart Study Group:

Diastolic dysfunction; hypertension; Statins; ACE inhibitor; Echocardiography

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Simvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors