Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury

Summary

Rationale:

Apart from their cholesterol lowering effects, statins have cholesterol-independent pleiotropic actions, such as upregulation of 5'-ectonucleotidase and up-regulation of NO-synthase that may increase tolerance against ischemia-reperfusion injury (IR-injury). Several animal studies have shown reduction of IR-injury as a result of statin treatment in both the heart and the kidney. Recently the investigators have shown, using Annexin A5 targeting after voluntary ischemic exercise to assess IR-injury, a protective effect of a 7 day oral rosuvastatin treatment. A three day treatment with atorvastatin however failed to reduce annexin targeting.

Assessment of the flow mediated dilation of the brachial artery as measure of endothelial (dys)function, is a validated model to research effects of possible protective strategies and perform mechanistic experiments on IR-injury in humans in vivo.

The investigators hypothesize that pretreatment with statins can increase endothelial tolerance against ischemia and reperfusion injury.

Objective:

To study the protective effect of pretreatment (both 3 day and 7 day) with rosuvastatin and atorvastatin on flow mediated dilation after 15 minutes ischemia and 15 minutes reperfusion.

Study design: placebo-controlled randomised double-blind trial

Study population: Healthy volunteers, age 18-50

Intervention: Treatment with either rosuvastatin 20 mg, atorvastatin 80mg or placebo during either 3 or 7 days

Main study parameters: Difference in flow mediated dilation before and after 15 minutes ischemia.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment with rosuvastatin or atorvastatin is not expected to harm the volunteers. Most reported side effects of rosuvastatin and atorvastatin are gastro-intestinal complains and myalgia. The volunteers will not benefit directly from participating in this study.

Conditions

• Ischemia Reperfusion Injury
• Endothelial Dysfunction

Interventions

DRUG

rosuvastatin

rosuvastatin 20 mg/day for 3 days.

DRUG

atorvastatin 3 days

atorvastatin 80 mg/day for 3 days.

DRUG

placebo

placebo for 3 days.

DRUG

rosuvastatin 7 days

rosuvastatin 20 mg/day for 7 days

DRUG

atorvastatin 7 days

atorvastatin 80 mg/day for 7 days.

DRUG

placebo 7 days

placebo 7 days

Sponsors & Collaborators

• Radboud University Medical Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-09-30

Primary Completion

2010-02-28

Completion

2010-03-31

Countries

• Netherlands

Study Locations