NIHR Signal A statin drug during admission for heart surgery did not prevent an irregular heart beat

Published on 14 July 2016

The statin, rosuvastatin, taken by adults before and after heart surgery, did not prevent atrial fibrillation or heart muscle injury compared to placebo. Acute kidney injury was more common for adults who received rosuvastatin.

Atrial fibrillation (AF) is a type of irregular heart rhythm which is relatively common after heart surgery. A previous review of published research suggested that atrial fibrillation might be half as common with perioperative atorvastatin therapy, but the evidence was not reliable.

This large trial included 1,922 adults from a hospital in Hong Kong mostly awaiting coronary-artery bypass graft. Rosuvastatin 20mg daily was not shown to reduce atrial fibrillation, nor heart muscle damage. It did, as expected, reduce “bad” cholesterol and C-reactive protein, a marker of inflammation, compared to the inactive placebo.

Statins do have proven longer term benefits in reducing further damage to the coronary arteries and deaths from heart disease.

A statin drug during admission for heart surgery did not prevent an irregular heart beat

Why was this study needed?

Atrial fibrillation can occur in about 20% of people undergoing heart surgery and if not corrected is associated with poorer recovery and reduced ability to exercise.

Although a review of trials has suggested that statin therapy around the time of surgery might reduce some complications the studies were small and may have been susceptible to bias. The current trial aimed to compare use of rosuvastatin against placebo in a randomised controlled trial with a larger sample size.

What did this study do?

The STICS was a randomised controlled trial of 1,922 adults awaiting planned cardiac surgery, mostly coronary-artery bypass graft and some surgical aortic valve replacements. Adults were eligible if they had normal heart rhythms and were not taking medication for abnormal heart rhythms other than beta blockers.

Half were randomised to receive rosuvastatin 20 mg daily, and half to receive placebo daily for up to eight days before surgery (pre-operatively) and five days following surgery (post-operatively).

The researchers looked for atrial fibrillation, using continuous electrocardiographic monitoring, and for evidence of myocardial (heart muscle) injury, using standard blood tests, up to five days after surgery.

Adverse events, length of stay in hospital and intensive care and heart and liver function were also assessed.

What did it find?

  • The rate of post-operative atrial fibrillation within five days was not reduced by rosuvastatin (21.1%) compared to placebo (20.5%), (odds ratio 1.04, 95% confidence interval [CI] 0.84 to 1.30).
  • Troponin-I levels, which test for post-operative heart muscle injury, were no different in those that received rosuvastatin compared to those that received placebo (between group difference 1%, 95% CI 9 to 13).
  • Higher plasma creatinine levels indicative of abnormal kidney function were seen with rosuvastatin compared to placebo. There was also a higher rate of acute kidney injury within two days of surgery for adults who received rosuvastatin (24.7%) compared to placebo (19.3%) p=0.005.
  • There was no difference in length of hospital or intensive care stay or serious adverse events post-operatively between those that received rosuvastatin or placebo.

What does current guidance say on this issue?

European and US guidelines recommend taking perioperative statins to prevent atrial fibrillation and other in-hospital complications after cardiac surgery. However, these recommendations were based on small trials with limitations. Rosuvastatin was not specifically recommended over other statins.

NICE considers rosuvastatin 20 mg daily (the trial dose) a high intensity statin along with atorvastatin 20 to 80 mg daily and simvastatin 80 mg daily (the MHRA has a safety warning on simvastatin 80 mg due to muscle damage).

What are the implications?

For adults awaiting elective cardiac surgery, perioperative statin therapy with rosuvastatin 20 mg daily was not shown to reduce the risk of in-hospital atrial fibrillation or perioperative myocardial injury.

Acute kidney injury was more common in adults who received rosuvastatin than placebo although there was no difference in the number of other serious adverse events over the period of the study.

Citation and Funding

Zheng Z, Jayaram R, Jiang L, et al. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med. 2016;374(18):1744-53.

This project was funded by the British Heart Foundation, the European Network for Translational Research in Atrial Fibrillation of the European Commission Seventh Framework Program, the Oxford Biomedical Research Centre, and the UK Medical Research Council and by a small unrestricted grant from AstraZeneca.

Bibliography

Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58(24):e123-210.

January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-76.

NHS Choices. Atrial fibrillation. London: Department of Health; updated 2015.

NICE. Cardiovascular disease: risk assessment and reduction, including lipid modification. CG181. London: National Institute of Health and Care Excellence; 2014.

NICE. Lipid-modifying drugs. KTT3. London: National Institute for Health and Care Excellence; 2016.

The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology. Guidelines for the management of atrial fibrillation. Europace. 2010;12:1360-420.

Why was this study needed?

Atrial fibrillation can occur in about 20% of people undergoing heart surgery and if not corrected is associated with poorer recovery and reduced ability to exercise.

Although a review of trials has suggested that statin therapy around the time of surgery might reduce some complications the studies were small and may have been susceptible to bias. The current trial aimed to compare use of rosuvastatin against placebo in a randomised controlled trial with a larger sample size.

What did this study do?

The STICS was a randomised controlled trial of 1,922 adults awaiting planned cardiac surgery, mostly coronary-artery bypass graft and some surgical aortic valve replacements. Adults were eligible if they had normal heart rhythms and were not taking medication for abnormal heart rhythms other than beta blockers.

Half were randomised to receive rosuvastatin 20 mg daily, and half to receive placebo daily for up to eight days before surgery (pre-operatively) and five days following surgery (post-operatively).

The researchers looked for atrial fibrillation, using continuous electrocardiographic monitoring, and for evidence of myocardial (heart muscle) injury, using standard blood tests, up to five days after surgery.

Adverse events, length of stay in hospital and intensive care and heart and liver function were also assessed.

What did it find?

  • The rate of post-operative atrial fibrillation within five days was not reduced by rosuvastatin (21.1%) compared to placebo (20.5%), (odds ratio 1.04, 95% confidence interval [CI] 0.84 to 1.30).
  • Troponin-I levels, which test for post-operative heart muscle injury, were no different in those that received rosuvastatin compared to those that received placebo (between group difference 1%, 95% CI 9 to 13).
  • Higher plasma creatinine levels indicative of abnormal kidney function were seen with rosuvastatin compared to placebo. There was also a higher rate of acute kidney injury within two days of surgery for adults who received rosuvastatin (24.7%) compared to placebo (19.3%) p=0.005.
  • There was no difference in length of hospital or intensive care stay or serious adverse events post-operatively between those that received rosuvastatin or placebo.

What does current guidance say on this issue?

European and US guidelines recommend taking perioperative statins to prevent atrial fibrillation and other in-hospital complications after cardiac surgery. However, these recommendations were based on small trials with limitations. Rosuvastatin was not specifically recommended over other statins.

NICE considers rosuvastatin 20 mg daily (the trial dose) a high intensity statin along with atorvastatin 20 to 80 mg daily and simvastatin 80 mg daily (the MHRA has a safety warning on simvastatin 80 mg due to muscle damage).

What are the implications?

For adults awaiting elective cardiac surgery, perioperative statin therapy with rosuvastatin 20 mg daily was not shown to reduce the risk of in-hospital atrial fibrillation or perioperative myocardial injury.

Acute kidney injury was more common in adults who received rosuvastatin than placebo although there was no difference in the number of other serious adverse events over the period of the study.

Citation and Funding

Zheng Z, Jayaram R, Jiang L, et al. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med. 2016;374(18):1744-53.

This project was funded by the British Heart Foundation, the European Network for Translational Research in Atrial Fibrillation of the European Commission Seventh Framework Program, the Oxford Biomedical Research Centre, and the UK Medical Research Council and by a small unrestricted grant from AstraZeneca.

Bibliography

Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58(24):e123-210.

January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-76.

NHS Choices. Atrial fibrillation. London: Department of Health; updated 2015.

NICE. Cardiovascular disease: risk assessment and reduction, including lipid modification. CG181. London: National Institute of Health and Care Excellence; 2014.

NICE. Lipid-modifying drugs. KTT3. London: National Institute for Health and Care Excellence; 2016.

The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology. Guidelines for the management of atrial fibrillation. Europace. 2010;12:1360-420.

Perioperative Rosuvastatin in Cardiac Surgery

Published on 5 May 2016

Z Zheng, R Jayaram, L Jiang, J Emberson, Y Zhao, Q Li, J Du, S Guarguagli, M Hill, Z Chen, R Collins, and B Casadei

The New England Journal of Medicine , 2016

Background Complications after cardiac surgery are common and lead to substantial increases in morbidity and mortality. Meta-analyses of small randomized trials have suggested that perioperative statin therapy can prevent some of these complications. Methods We randomly assigned 1922 patients in sinus rhythm who were scheduled for elective cardiac surgery to receive perioperative rosuvastatin (at a dose of 20 mg daily) or placebo. The primary outcomes were postoperative atrial fibrillation within 5 days after surgery, as assessed by Holter electrocardiographic monitoring, and myocardial injury within 120 hours after surgery, as assessed by serial measurements of the cardiac troponin I concentration. Secondary outcomes included major in-hospital adverse events, duration of stay in the hospital and intensive care unit, left ventricular and renal function, and blood biomarkers. Results The concentrations of low-density lipoprotein cholesterol and C-reactive protein after surgery were lower in patients assigned to rosuvastatin than in those assigned to placebo (P<0.001). However, the rate of postoperative atrial fibrillation did not differ significantly between the rosuvastatin group and the placebo group (21.1% and 20.5%, respectively; odds ratio 1.04; 95% confidence interval [CI], 0.84 to 1.30; P=0.72), nor did the area under the troponin I–release curve (102 ng×hour per milliliter and 100 ng×hour per milliliter, respectively; between-group difference, 1%; 95% CI, −9 to 13; P=0.80). Subgroup analyses did not indicate benefit in any category of patient. Rosuvastatin therapy did not result in beneficial effects on any of the secondary outcomes but was associated with a significant absolute (±SE) excess of 5.4±1.9 percentage points in the rate of postoperative acute kidney injury (P=0.005). Conclusions In this trial, perioperative statin therapy did not prevent postoperative atrial fibrillation or perioperative myocardial damage in patients undergoing elective cardiac surgery. Acute kidney injury was more common with rosuvastatin. (Funded by the British Heart Foundation and others

Expert commentary

Severe complications following cardiac surgery are commonly attributed to inflammation. Statins have well documented anti-inflammatory effects. On the basis of evidence from several small clinical trials, existing treatment guidelines recommend that patients undergoing cardiac surgery receive statin therapy routinely.

The STICS trial evaluated the effects of preoperative administration of statins in more cardiac surgery patients than all the previous trials combined. The major finding from the trial was that statins reduced levels of inflammation, but did not reduce complication rates. In fact, statin administration increased rates of post-surgery kidney damage.

These results highlight important limitations of previous studies and suggest that current treatment guidelines should be revised. Most importantly these results challenge the prevailing wisdom that post cardiac surgery complications are caused by inflammation.

Gavin Murphy, British Heart Foundation Professor of Cardiac Surgery, University of Leicester; Honorary Consultant Cardiac Surgeon, University Hospitals of Leicester NHS Trust

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