Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD)

Hospital do Coracao

Status and phase: Completed; Phase 3

Conditions: Aortic Aneurism; Peripheral Vascular Disease; Myocardial Infarction

Treatments: Drug: Placebo; Drug: Atorvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT01543555

02/15/2012

Details and patient eligibility

About

Patients submitted to noncardiac surgeries are at increased risk of serious cardiovascular complications. Statins have shown to lower cholesterol levels and reduce cardiovascular events in other scenarios. The objective of this study is to explore the effects of atorvastatin, as compared with placebo, on the 30-day risk of a composite of death, nonfatal Myocardial Injury after Noncardiac Surgery (MINS), or stroke among patients who undergo noncardiac surgery.

Full description

Cardiovascular complications, such as myocardial infarction (MI) and stroke are common in the perioperative period of noncardiac surgeries. To the moment there are no safe and effective interventions to reduce vascular events in this scenario. Data from observational studies and small-sized randomized controlled trials (RCTs) have shown promising results in terms of risk reduction. In addition, experimental data have indicated that statins have acute anti-inflammatory properties, which promote the stabilization of atherosclerotic lesions and, therefore, might reduce the risk of MI, even in the short term. This study was designed to explore the effects of atorvastatin, as compared with placebo, on the 30-day risk of a composite of death, nonfatal Myocardial Injury after Noncardiac Surgery (MINS), or stroke among patients who undergo noncardiac surgery.

The study was conducted in accordance with the prespecified protocol and reached successful enrollment rates when, by the end of 2014 the steering committee was invited to join an international initiative and participate in a much larger clinical trial to investigate this relevant question. Due to this outstanding possibility, the steering committee decided to redesign the study which is now formatted as an exploratory trial. As described, the study was completed with the inclusion of 648 participants in June, 2015.

Enrollment: 648 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients older than 40 years-old undergoing non-cardiac surgery with an expected hospital stay of at least 24hs and that fulfills any one of the following criteria:

A) Established vascular disease:

i) Major vascular surgery ii) All types of surgery in patients with overt atherosclerosis (any significant or symptomatic coronary, cerebral or peripheral artery disease)

B) Without established vascular disease:

At least 3 risk factors for cardiovascular complications:

1. Major surgery;
2. Emergency surgery;
3. Previous history of heart failure;
4. diabetes;
5. Arterial hypertension;
6. Smoking habit along the last two years;
7. chronic kidney disease (creatinine greater than 2mg/dl);
8. Patients older than 70 years.

Exclusion criteria

• Previous intolerance to statins
• Current rhabdomyolysis
• Current use of statins
• Severe Liver Failure (CHILD-PUGH SCORE C)
• Breast-feeding or pregnancy
• Low-risk surgeries

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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648 participants in 2 patient groups, including a placebo group

Atorvastatin active

Experimental group

Description:

Atorvastatin 80mg anytime within 18 hours before surgery. A postoperative 40mg atorvastatin dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg atorvastatin daily for the next seven days.

Treatment:

Drug: Atorvastatin

Placebo

Placebo Comparator group

Description:

Matching placebo 80mg anytime within 18 hours before surgery. A postoperative 40mg placebo dose administered at least 12 hours after the 80mg loading dose. Subsequently, 40mg placebo daily for the next seven days.

Treatment:

Drug: Placebo