Timing and Dose Matters When It Comes to Statin Therapy Before CABG Surgery

Despite the positive findings, one expert believes there is more to learn about the timing and duration of statin therapy in this group.

Timing and Dose Matters When It Comes to Statin Therapy Before CABG Surgery

Taking a statin within 1 day of coronary artery bypass graft surgery is associated with a significantly lower risk of all-cause mortality at 30 days when compared with patients who take a preoperative statin outside of the 24-hour window, new research shows.

Additionally, taking atorvastatin 20 mg or another statin equivalent in intensity is also associated with a significantly lower risk of death at 30 days when compared with less potent therapy.

“Our findings suggest that preoperative statin therapy is associated with a significant reduction of perioperative mortality after CABG operation,” according to lead investigator Michael Curtis, MD (Baylor College of Medicine, Houston, TX), and colleagues. “Moreover, we found that the timing and dose of statin are independently associated with mortality reduction.”

Islam Elgendy, MD (University of Florida, Jacksonville), who was not involved in this observational analysis but who has previously studied the effects of starting statin therapy prior to CABG, said there is now “ample data” to support the continuation of statin therapy in all patients undergoing coronary bypass surgery (unless contraindicated).

“This is contradictory to some beliefs that the discontinuation of statins is better given the potential risks of statin therapy, such as rhabdomyolysis, which could be accentuated due to the surgery,” Elgendy told TCTMD. “This study adds that the benefit is more pronounced with the higher doses of atorvastatin, which is in line with the hyperlipidemia guidelines that recommend high intensity statin therapy in these patients.”

The American College of Cardiology and American Heart Association recommend all patients undergoing CABG surgery receive statin therapy (class I, level of evidence A) unless contraindicated, and even advise patients undergoing urgent or emergency CABG be started on a high-intensity statin if they are not already taking one (class IIa, level of evidence C).

The European Society of Cardiology and European Association for Cardiothoracic Surgery also recommend preoperative statin therapy for patients undergoing CABG surgery.

Nuances of Statins Before CABG Surgery

Despite the recommendations, Curtis and colleagues point out there has been little investigation into the “nuances” of statin therapy before cardiac surgery. In their study, which was published online March 17, 2017, in the Annals of Thoracic Surgery, they retrospectively analyzed data from 3,025 isolated CABG procedures at their institution to assess the effect of timing and dose of statin therapy on perioperative outcomes.

Patients were classified into groups based on when they received preoperative statin therapy: 1,788 patients received a statin within 24 hours of surgery, 452 patients within 24-72 hours, and 781 received no statin or took it more than 72 hours prior to the procedure.

The 30-day mortality rate was 3.8% for those not taking a statin (or who took it more than 72 hours before CABG), 2.9% for those who a statin 24-72 hours before surgery, and 1.7% for those who took a statin within 24 hours of surgery (P < 0.01). In a multivariate-adjusted analysis, the administration of a statin within 24 hours of surgery was associated with a significant 62% reduction in 30-day mortality when compared with no statin therapy/beyond 72 hours. There was no mortality benefit for patients who took a statin within 24-72 hours of surgery (OR 0.63; 95% CI 0.31-1.29) when compared with the no statin/beyond 72-hour group.

Similarly, in a propensity-matched analysis of 2,070 patients, those given a statin within 24 hours of CABG surgery had a significant 48% lower risk of death at 30 days when compared with those who received a statin beyond 24 hours (or no statin).

Next, the researchers examined the effect of dose. In total, 44% of patients were taking more than atorvastatin 20 mg or equivalent, 31% were taking less than atorvastatin 20 mg or equivalent, and 25% were taking no statin. The 30-day mortality rate was 3.8% for those taking no statin, 2.1% for patients taking more than atorvastatin 20 mg, and 1.8% for those taking atorvastatin 20 mg or less.

In the multivariate-adjusted model, both doses of atorvastatin (or equivalent intensity statins) were associated with reductions in mortality compared with no statin therapy. In a propensity-matched model of 1,098 patients, those taking 20 mg or more of atorvastatin had a 68% lower risk of death at 30 days when compared with no statin therapy, but there was no mortality benefit among patients taking 20 mg atorvastatin or less.

To TCTMD, Elgendy pointed to the anti-inflammatory effects of statins, the so-called pleiotropic effects exerted by the drugs beyond LDL-cholesterol lowering. “Bypass surgery is associated with a severe inflammatory response, which is implicated in the mortality and morbidity associated with bypass surgery, and statin therapy has been demonstrated to attenuate this effect by reducing some of these inflammatory surrogates. such as C-reactive protein and thromboxane A2,” he said.

What the Study Doesn’t Show . . .

While the present study confirms the benefits of statins in patients undergoing CABG surgery, and supports the clinical guidelines, Elgendy said there is an important limitation. The study investigators did not provide any data regarding clinical outcomes among patients who were on prior statin therapy and continued with treatment right up until surgery and those patients who started statin therapy in the days before the operation (de novo initiation of statins).

Elgendy noted that the recently published Statin Therapy in Cardiac Surgery (STICS) study challenged the benefits of newly initiated rosuvastatin in patients undergoing cardiac surgery. In STICS, treatment with rosuvastatin 20 mg started 8 days before and for 5 days after surgery failed to reduce the incidence of new-onset atrial fibrillation and myocardial injury. It was also associated with an increased risk of acute kidney injury.   

“The study by Curtis et al supports the benefit of statin continuation, [but] based on the results of STICS trial, the de novo administration of rosuvastatin might not be beneficial,” said Elgendy.

The Statin Recapture Therapy Before Coronary Artery Bypass Grafting (START-CABG) is a large-scale study conducted at 8 European centers investigating the potential benefits of "reloading" patients 12 and 2 hours prior to bypass surgery with high-dose statin therapy. “This trial will further inform us about whether additional high-intensity statin reloading would be of benefit,” added Elgendy.         

Sources
  • Curtis M, Deng Y, Lee VV, et al. Effect of dose and timing of preoperative statins on mortality after coronary artery bypass surgery. Ann Thorac Surg. 2017;Epub ahead of print.

Disclosures
  • Authors report no conflicts of interest.
  • Elgendy reports no conflicts of interest.

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