Statin Therapy In Atrial Refractoriness and Reperfusion Injury
Condition: Disorder; Heart, Functional, Postoperative, Cardiac Surgery; Cardiac Insufficiency Following Cardiac Surgery; Atrial Fibrillation; Ischaemia-reperfusion Injury
MeSH terms: Atrial Fibrillation; Reperfusion Injury; Heart Failure; Ischemia
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients with coronary artery disease are often prescribed drugs called statins because
      research has shown that, by lowering cholesterol, they reduce the risk of having a heart
      attack or other complications in the long-term. Experimental studies have suggested that
      statins may also have rapid anti-inflammatory, anti-oxidant and anti arrhythmic actions;
      however, whether these effects are of any benefit to patients remains to be proven. The
      purpose of STARR trial (Statin Therapy in Atrial Refractoriness and Reperfusion injury) is to
      evaluate whether a short course of a commonly used statin (atorvastatin, 80 mg once a day)
      decreases inflammation and stabilises electrical properties of the upper chamber of the heart
      in the post operative period of patients undergoing cardiac surgery on the heart-lung machine
      either for valve replacement and/or coronary artery bypass grafting. It will also examine
      whether this treatment can protect the heart from sustaining tissue damage when blood supply
      is restored after a period of ischaemia during the course of the surgery.In addition it will
      also explore the impact of this intervention on biology of the vessels used for bypass
      surgery and the fat tissue in the vicinity of the heart & blood vessels.
    

Detailed description: 
      Evidence that pre- or perioperative statin treatment may reduce the occurrence of
      post-operative atrial fibrillation and improve clinical outcome in patients undergoing
      coronary artery bypass graft (CABG) or major vascular surgery has been largely generated by
      observational studies. In a recent meta-analysis of 6 randomized trials (of which only 2 had
      postoperative atrial fibrillation (AF) as a predefined outcome) evaluating the use of
      perioperative statin treatment in patients undergoing cardiac surgery (n=651 patients in
      total - study size between 40 and 200 patients), statin use was found to reduce the patients'
      relative risk of developing postoperative AF by 43% (RR 0.57, 95%CI 0.45,0.72) and their
      absolute risk by 14% (95% CI 8%,20%). Although these findings would be consistent with a
      rapid and, possibly, lipid-independent antiarrhythmic effect of statins, they have important
      limitations (e.g., single-centre, small size, lack of continuous ECG monitoring, mostly
      "ancillary" findings") and less bearing on current clinical practice, as they mostly included
      statin-naïve patients. For these reasons, the recent guidelines for the management of AF have
      not given a strong recommendation for the use of statins in the prevention of postoperative
      AF. Thus, whether intensive statin treatment in the perioperative period can confer cardio
      protection by reduction of atrial oxidative stress & improvement in atrial electrical
      remodelling remains to be demonstrated.As endothelial function is a strong determinant of
      clinical outcomes, improvement of vascular redox state & increase in nitric oxide
      bioavailability of arterial & venous grafts of patients undergoing cardiac surgery may
      improve post operative outcomes.However it is still unclear whether higher doses of
      atorvastatin could confer additional beneficial effects on human vessels. Adipose tissue (AT)
      by releasing vasoactive molecules & adipokines can affect myocardial and vascular biology.
      Recent evidence suggests that statins may favourably alter AT biosynthetic activity and
      increase the AT release of adiponectin (An adipokine that has been shown to have
      anti-inflammatory and anti-atherogenic effects) in turn improving the vascular & myocardial
      redox state. However there are only limited data on the effects of statins on human adipose
      tissue biology and most findings to date are based on cell lines and/or relevant mouse
      models.
    

Intervention name(s): Atorvastatin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Atorvastatin (80 mg od) started not earlier than 6 days before surgery and continued until the 5th post-operative day included;; Placebo started not earlier than 6 days before surgery and continued until the 5th post-operative day included;
Other intervention name(s): Lipitor; Sugar pill manufactured to mimic Atorvastatin 40mg tablet.
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Bypass Surgery, Coronary Artery; Atrial fibrillation; Ischaemia-reperfusion injury; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Statins, HMG-CoA