Author + information
Scirica BM, Morrow DA, Cannon CP, Ray KK, Sabatine MS, Jarolim P, Shui A, McCabe CH, Braunwald E, for the PROVE IT–TIMI 22 Investigators. Intensive Statin Therapy and the Risk of Hospitalization for Heart Failure After an Acute Coronary Syndrome in the PROVE IT–TIMI 22 Study. J Am Coll Cardiol 2006;47:2326–31.
Explanation of Correction
During subsequent analyses of the PROVE IT–TIMI 22 study database, we discovered an error in the original coding that incorrectly counted the primary endpoint of interest for this manuscript—the first occurrence of hospitalization for heart failure.
As a result, the original coding did not account for all episodes of hospitalization for heart failure present in the database. In addition, the coding did not appropriately identify the timing of first occurrence of hospitalization for heart failure in all subjects. This issue led to an underestimate in all groups irrespective of statin or BNP status.
Using the correct coding, we have repeated all analyses presented in this manuscript. We provide a corrected version of the Results section for the Abstract and Body Text as well as updated figures to reflect these changes.
Even though the correct coding numerically changes most of the results in the manuscript, there were no qualitative differences based on the updated results. All the analyses examining the relationships between atorvastatin, BNP, and hospitalization for heart failure reported in the original are consistent with the updated coding. Therefore, our discussion and conclusions remain valid and have not been amended.
Treatment with atorvastatin 80 mg significantly reduced the rate of hospitalization for HF (2.3% vs. 3.9%, hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.45 to 0.91, p = 0.012) independently of a recurrent myocardial infarction or prior history of HF. The risk of HF increased steadily with increasing quartiles of BNP (HR: 2.45, 95% CI: 1.33 to 4.52, p = 0.004) for the highest quartile compared with the lowest). Among patients with elevated levels of BNP (>80 pg/ml), treatment with atorvastatin significantly reduced the risk of HF compared with pravastatin (HR: 0.50, 95% CI: 0.27 to 0.93, p = 0.028). A meta-analysis of four trials that included 27,546 patients demonstrates a 27% reduction in the odds of hospitalization for HF with intensive statin therapy.
Benefit of Intensive Statin Therapy of HF
This analysis included all 4,162 patients enrolled in the PROVE IT–TIMI 22 study. As previously described, patients were enrolled a median of seven days after onset of their index event, and there were no differences between treatment groups in terms of age, gender, index diagnosis, or rates of prior myocardial infarction, revascularization, diabetes, or hypertension (1). There were also no differences in the rate of prior HF between treatment arms (3.2% for atorvastatin vs. 3.5% for pravastatin, p = NS), the rate of ST-segment elevation myocardial infarction (35.6% vs. 33.4%, p = NS), or the rate of PCI for the index event (68.7% vs. 69.1%, p = NS).
Treatment with atorvastatin 80 mg was associated with a significant 36% reduction in the rate of hospitalization for HF (2.3% vs. 3.9% [HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012]) (Fig. 1). This reduction in the risk of HF was not attenuated when controlling for recurrent myocardial infarction (HR: 0.68, 95% CI: 0.48 to 0.96, p = 0.030) or a history of prior HF (HR: 0.63, 95% CI: 0.44 to 0.90, p = 0.011). The benefit of atorvastatin 80 mg was similar after excluding all patients (n = 40) who developed HF after having suffered a recurrent myocardial infarction or recurrent ischemia requiring hospitalization or revascularization (HR: 0.54, 95% CI: 0.35 to 0.84, p = 0.006). The benefit of intensive statin therapy was also similar when the first 30 days after randomization were included in the analysis (HR: 0.68, 95% CI: 0.49 to 0.93, p = 0.016).
BNP and the Risk of HF
Compared with those without subsequent hospitalization for HF, patients who developed HF had higher baseline levels of BNP (median 55 vs. 31 pg/ml, p < 0.001) and were more likely to have a concentration of BNP >80 pg/ml (39.0% vs. 18.2%, p < 0.001). The concentration of BNP showed a significant graded relationship with the risk of HF, with a significantly higher risk of HF among patients in the highest (BNP >65 pg/ml) compared with the lowest quartile (BNP <15 pg/ml, adjusted HR: 2.45, 95% CI: 1.33 to 4.52, p = 0.004).
Intensive Statin Therapy and BNP
There was no difference in baseline levels of BNP between treatment arms (31 vs. 32 ng/l, p = NS). When examined by elevated (>80 pg/ml) or normal (>80 pg/ml) baseline levels of BNP and treatment arm, patients with elevated baseline levels (>80 pg/ml) of BNP randomized to pravastatin had the highest rate of hospitalization for HF (8.6%) followed by patients with an elevated BNP randomized to atorvastatin (4.1%), patients with normal BNP randomized to pravastatin (2.8%), and then patients normal baseline levels of BNP randomized to atorvastatin were at 1.8% (Fig. 2).
Assignment to atorvastatin significantly reduced the risk of the development of HF among patients with elevated levels of BNP (HR: 0.50, 95% CI: 0.27 to 0.93, p = 0.028). Although patients with such elevated levels of BNP had a greater absolute reduction in the risk of HF (4.5%) with intensive statin therapy than patients with low BNP (1.0%, HR: 0.72, 95% CI: 0.45 to 1.14, p = 0.16), formal statistical testing for an interaction of BNP with the effect of treatment was not significant (p interaction = 0.36).
Meta-Analysis of Intensive Statin Therapy Trials
A meta-analysis of the four published large, randomized trials that compared intensive statin therapy with moderate statin therapy and that reported the rates of congestive HF demonstrates a highly significant 27% reduction in the odds of hospitalization for HF in (n = 27,546, OR: 0.73, 95% CI: 0.64 to 0.84, p < 0.001) (chi-square for heterogeneity = 1.22 [degrees of freedom = 3], p = 0.747) (Fig. 3).
- American College of Cardiology Foundation