Statin Reloading Improves Clinical Outcomes in Stable PCI Patients

PARIS, France—A loading dose of rosuvastatin or atorvastatin prior to percutaneous coronary intervention (PCI) in stable patients who are already on chronic statin therapy improves clinical outcomes out to 12 months, according to results from the ROMA II trial presented Thursday, May 17, at EuroPCR 2012.

At last year’s EuroPCR meeting, Gennaro Sardella, MD, of “Sapienza” University of Rome (Rome, Italy), presented results of the ROMA (ROsuvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of MyocArdial periprocedural necrosis) trial. The findings showed that a 40-mg loading dose of rosuvastatin (Crestor, Astra Zeneca) was an independent predictor of reduced MACCE (cardiac death, MI, or stroke) at 12 months in statin-naive patients.

For the ROMA II Reload trial, Dr. Sardella and colleagues randomized 350 patients undergoing elective PCI to a loading dose of 40-mg rosuvastatin or 80-mg atorvastatin (Lipitor, Pfizor) within 24 hours prior to the procedure. A control group of 100 registry patients received standard therapy (aspirin and clopidogrel the day before PCI). All patients had already been receiving statin therapy.

Baseline clinical and angiographic characteristics were similar among the 3 groups. All patients presented with stable angina.

Reload Reduces Pair of Primary Endpoints

Both rosuvastatin and atorvastatin showed similar results for the co-primary endpoint of myonecrosis (CK-MB > 3 times ULN) at 12 hours post-procedure (7.1% vs. 6.1%; P = 0.643). This was also true at 24 hours (8.9% vs. 8.3%; P = 0.834). Importantly, both statin groups lowered the endpoint compared with the control group, which had 25% of patients exhibiting myonecrosis at 12 hours and 29.2% at 24 hours (P = 0.0001 vs. atorvastatin at both time points; P = 0.003 at 12 hours and P = 0.001 at 24 hours vs. rosuvastatin).

These results were maintained when evaluating troponin T levels greater than 0.1 ng/mL ULN. The exception was that atorvastatin showed a strong trend for lowering this endpoint compared with rosuvastatin at 24 hours post procedure (27.6% vs. 37.9%; P = 0.06).

At 30 days, the other co-primary endpoint of cumulative MACCE was equivalent between the rosuvastatin and atorvastatin groups, both showing improved outcomes compared with controls. This was sustained at 6 and 12 months (tables 1 and 2).

Table 1. ROMA II Reload: 6-Month MACCE

 

Rosuvastatin
(n = 175)

Atorvastatin
(n = 175)

Controls
(n = 100)

P Valuea

MACCE

18%

16%

36%

0.0001

Cardiac Death

0

0

1%

0.185

Periprocedural MI

16%

14%

29%

0.0001

Spontaneous MI

1%

0

2%

0.06

TVR

1%

2%

2%

0.567

Stroke

0

0

3%

0.03

Rehospitalization

2%

1%

6%

0.021

a P values for either statin group compared with controls.

 

Table 1. ROMA II Reload: 12-Month MACCE

 

Rosuvastatin
(n = 175)

Atorvastatin
(n = 175)

Controls
(n = 100)

P Valuea

MACCE

20%

21%

41%

0.0001

Cardiac Death

1%

2%

2%

0.562

Periprocedural MI

16%

14%

29%

0.0001

Spontaneous MI

2%

0

3%

0.06

TVR

1%

5%

5%

0.09

Stroke

0

0

3%

0.03

Rehospitalization

3%

6%

11%

0.011

a P values for either statin group compared with controls.

On 12-month landmark analysis, treatment with either statin showed improved survival vs. controls (P = 0.038), and on multivariable analysis, reloading with atorvastatin or rosuvastatin independently predicted reduced MACCE (HR 0.18; 95% CI 0.081-0.401; P = 0.0001).

“The efficacy of statin pretreatment seems to improve the procedural and long-term clinical outcome in stable PCI patients [on chronic statin therapy],” Dr. Sardella concluded, adding that while the drugs showed similar effects on procedural and mid- to long-term outcomes, “both statins confirmed their beneficial effects compared with the absence of statin pretreatment.”

Both audience and panel members sought to understand how statin reloading could lead to such improvements. “The mechanism of action of statins, as you know, is pleiotropic . . . and anti-inflammatory effects on plaque,” Dr. Sardella explained, noting that the only baseline difference that might have come into play was a slightly higher angiographic risk among those receiving statin reloading compared with controls.

“It’s the anti-inflammatory effects,” Dr. Sardella reiterated. “Maybe these anti-inflammatory effects can control periprocedural myonecrosis.” Regardless of the mechanism of action, given the findings from the previous ROMA trial and several other studies, “we are not surprised by these results,” he said.

Where’s the Magic?

Panel member Spencer B. King III, MD, of Saint Joseph's Heart and Vascular Institute (Atlanta, GA), wondered when controls had their last dose of chronic statin therapy and how high their doses were, especially since 63% of the control group were already on rosuvastatin or atorvastatin. “Is there something magic about having a high level at the time of the procedure? Does that explain some of this difference?” he asked.

Dr. Sardella did not report the mean control doses or ranges, though he indicated that chronic therapy dosing was much lower than the reloading doses.

Panel member Stefan James, MD, PhD, of Uppsala University Hospital (Uppsala, Sweden), pointed out that in one sense, the trial was negative, since the hypothesis was to show a difference in outcomes between rosuvastatin and atorvastatin, and the 2 proved equivalent.

Dr. Sardella assured that the similar outcomes with both lipid-lowering drugs does not take away from the finding that “both statins were superior to no statin reloading.”

Study Details

Patients receiving rosuvastatin (60.8%) and atorvastatin (59.3%) showed a trend for more type B2/C lesions than controls (51%; P = 0.091 vs. both statin groups). Patients in the 2 reloading groups also showed a trend for a longer mean stent length than controls (26.5 mm with rosuvastatin, 27.5 mm with atorvastatin vs. 20.8 mm with controls; P = 0.079).

 

Source:

Sardella G. Comparison of high reloading ROsuvastatin and atorvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of MyocArdial periprocedural necrosis: ROMA II Reload. Presented at: EuroPCR; May 17, 2012; Paris, France. 

Disclosures:

  • Dr. Sardella reported no relevant conflicts of interest.

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