Clinical trial NCT01543555: Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose
Official title: Multicenter Randomized Controlled Trial of Loading Dose Statins for the Prevention of Cardiovascular Complications in High-Risk Non-Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Infarction
Peripheral Vascular Disease
Aortic Aneurism
Keywords: myocardial infarction
statin
perioperative care
peripheral vascular diseases
anesthesiology
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
First posted: 2012-03-05
Enrollment: 648
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite outcome
timeFrame: 30 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: 30 days
measure: Myocardial injury after noncardiac surgery (MINS)
timeFrame: 30 days
measure: Stroke
timeFrame: 30 days
measure: Myocardial infarction
timeFrame: 30 days
measure: Cardiovascular death
timeFrame: 30 days
measure: Pulmonary embolism
timeFrame: 30 days
measure: Deep venous thrombosis
timeFrame: 30 days
measure: Clinically relevant atrial fibrillation
timeFrame: 30 days
measure: Rhabdomyolysis
timeFrame: 30 days
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital do Coração
state: SP
Study officials:
affiliation: Hospital do Coração
name: Otávio Berwanger, MD, PhD
role: STUDY_CHAIR
affiliation: Brazilian Clinical Research Institute
name: Renato D Lopes, MD Phd
role: STUDY_CHAIR
References:
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citation: Schouten O, Boersma E, Hoeks SE, Benner R, van Urk H, van Sambeek MR, Verhagen HJ, Khan NA, Dunkelgrun M, Bax JJ, Poldermans D; Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med. 2009 Sep 3;361(10):980-9. doi: 10.1056/NEJMoa0808207.
citation: Patti G, Cannon CP, Murphy SA, Mega S, Pasceri V, Briguori C, Colombo A, Yun KH, Jeong MH, Kim JS, Choi D, Bozbas H, Kinoshita M, Fukuda K, Jia XW, Hara H, Cay S, Di Sciascio G. Clinical benefit of statin pretreatment in patients undergoing percutaneous coronary intervention: a collaborative patient-level meta-analysis of 13 randomized studies. Circulation. 2011 Apr 19;123(15):1622-32. doi: 10.1161/CIRCULATIONAHA.110.002451. Epub 2011 Apr 4.