Immunosuppression With Prednisone for Restenosis Prevention
Immunosuppression With Prednisone for Restenosis Prevention
The detailed information regarding the baseline characteristics of patients enrolled in the study have been published previously and shown briefly in Table 1. As expected from its randomized nature, there were no differences among groups. As per protocol, 125 patients were actually treated with BMS, 127 with DES, and 122 with prednisone after BMS. At 1 year patients treated with BMS had a significantly worse event-free survival (80.8%) compared with those treated with the addition of oral prednisone (88%, HR: 0.505; 95% CI: 0.26–0.98, P = 0.04) or with DES (88.8%, HR: 0.388; 95% CI: 0.19–0.76, P = 0.006).
The median follow-up duration of the observation was 1447 days (IQ range 1210–1641) and was similar for the three groups, BMS: 1461 (1219–1644), prednisone: 1449 (1205–1664), and DES: 1420 (1213–1617).
Of the 375 patients enrolled, 4-year follow-up was available for 365 (123 patients with BMS: 98.4%, 121 patients treated with prednisone: 96.8%, and 121 patients with DES: 96.8%). Seven patients died before scheduled long-term follow-up visit; one patient in the DES group and one in the prednisone group could not be contacted (lost at follow-up) at 4 years; finally, one patient in the prednisone group refused to give consent for further contacts after 1 year. These three lost patients were considered as censored for the analyses at the moment of the latest clinical contact.
Patients receiving BMS alone when compared with those treated with prednisone or DES had a significantly lower event-free survival at 4 years. In fact, according to the intention to treat analysis it was 75.3% compared with 84.1% in the prednisone group (HR: 0.447; 95% CI: 0.29–0.80, P = 0.007) and 80.6% in the DES group (HR: 0.519; 95% CI: 0.29–0.93, P = 0.03) (Figure 1). The per-protocol analysis further reinforced this difference: prednisone, HR: 0.423; 95% CI: 0.24–0.74, P = 0.003 and DES, HR: 0.521; 95% CI: 0.28–0.99, P = 0.05. When major bleedings were included into the composite clinical endpoint, the net clinical outcome did not change, since only three cases of major bleeding (one per each treatment group) occurred between 1 and 4 years. Use of dual anti-platelet therapy at 1 year was more frequent in DES patients and the dual regimen was prolonged for another year in 28 BMS and 25 prednisone patients (Table 2). At 4 years, it was still used in 29 DES patients (23.2%), compared with 6 (4.8%) and 4 (3.2%) patients in the BMS and the prednisone groups, respectively, being this the only significant difference related to the medical treatment among groups at 4 years.
(Enlarge Image)
Figure 1.
Cumulative event-free survival (Kaplan–Meier analysis) of death, myocardial infarction, and ischaemia-driven target vessel revascularization at complete follow-up in the three study groups. Prednisone and drug-eluting stents groups show significantly higher event-free survival compared with bare metal stents patients.
Differences in terms of MACE and its landmark analysis (30 days, 1 year, between 1 and 4 years, and up to 4 years) are shown in Table 2 and Table 3. Mortality at 4 years was similar among the three groups and all cases were attributed a possible cardiovascular nature.
Spontaneous MI related to the target vessel within 1 year occurred in two patients of the BMS group (due to subacute stent thrombosis in one case, and due to occlusive restenosis in the second). At long term, three DES patients had spontaneous MI due to very late (definite) stent thrombosis. A possible stent thrombosis was adjudicated as a cause of sudden death in one DES patient (Table 3). All these events occurred under single anti-platelet regimen and had no correlation with recent therapeutic changes.
The need for TVR at long-term remained higher in the BMS group (23.2%), compared with prednisone (13.6%), or to DES (15.2%), although these differences did not attain statistical significance. Non-TVR rates in the prednisone group were 4.8%, compared with 7.2% in the BMS and 12% in the DES group, and the need for new revascularizations in other than the index sites (i.e. non-TLR plus non-TVR) was 9.6% in the prednisone group, compared with BMS (16.8%) or DES (20.8%).
The occurrence of newly diagnosed diabetes, peptic ulcer, refractory hypertension, auto-immune disease or cancer in the three groups was clinically irrelevant and homogeneously distributed.
At univariate analysis generic variables associated with the occurrence of MACE were baseline levels of creatinine (HR: 2.89, 95% CI: 0.96–8.69, P = 0.05), smoking habit (HR: 1.67, 95% CI: 1.05–2.66, P = 0.03), the presence of triple-vessel disease (HR: 1.53, 95% CI: 1.13–2.08, P = 0.005), the length (HR: 1.05, 95% CI: 1.00–1.01, P = 0.02), and the diameter of the stents (HR: 0.42, 95% CI: 0.25–0.67, P = 0.001). In the multivariate model, all the same variables, except the baseline creatinine levels, emerged as independent predictors on MACE. Treatment with prednisone significantly reduced the HR for the occurrence of MACE compared with BMS (HR = 0.447, 95% CI: 0.29–0.80, P = 0.007). The treatment with DES compared with BMS yielded an HR of 0.519 with a 95% CI: 0.29–0.97 and P = 0.05.
Results
The detailed information regarding the baseline characteristics of patients enrolled in the study have been published previously and shown briefly in Table 1. As expected from its randomized nature, there were no differences among groups. As per protocol, 125 patients were actually treated with BMS, 127 with DES, and 122 with prednisone after BMS. At 1 year patients treated with BMS had a significantly worse event-free survival (80.8%) compared with those treated with the addition of oral prednisone (88%, HR: 0.505; 95% CI: 0.26–0.98, P = 0.04) or with DES (88.8%, HR: 0.388; 95% CI: 0.19–0.76, P = 0.006).
The median follow-up duration of the observation was 1447 days (IQ range 1210–1641) and was similar for the three groups, BMS: 1461 (1219–1644), prednisone: 1449 (1205–1664), and DES: 1420 (1213–1617).
Of the 375 patients enrolled, 4-year follow-up was available for 365 (123 patients with BMS: 98.4%, 121 patients treated with prednisone: 96.8%, and 121 patients with DES: 96.8%). Seven patients died before scheduled long-term follow-up visit; one patient in the DES group and one in the prednisone group could not be contacted (lost at follow-up) at 4 years; finally, one patient in the prednisone group refused to give consent for further contacts after 1 year. These three lost patients were considered as censored for the analyses at the moment of the latest clinical contact.
Patients receiving BMS alone when compared with those treated with prednisone or DES had a significantly lower event-free survival at 4 years. In fact, according to the intention to treat analysis it was 75.3% compared with 84.1% in the prednisone group (HR: 0.447; 95% CI: 0.29–0.80, P = 0.007) and 80.6% in the DES group (HR: 0.519; 95% CI: 0.29–0.93, P = 0.03) (Figure 1). The per-protocol analysis further reinforced this difference: prednisone, HR: 0.423; 95% CI: 0.24–0.74, P = 0.003 and DES, HR: 0.521; 95% CI: 0.28–0.99, P = 0.05. When major bleedings were included into the composite clinical endpoint, the net clinical outcome did not change, since only three cases of major bleeding (one per each treatment group) occurred between 1 and 4 years. Use of dual anti-platelet therapy at 1 year was more frequent in DES patients and the dual regimen was prolonged for another year in 28 BMS and 25 prednisone patients (Table 2). At 4 years, it was still used in 29 DES patients (23.2%), compared with 6 (4.8%) and 4 (3.2%) patients in the BMS and the prednisone groups, respectively, being this the only significant difference related to the medical treatment among groups at 4 years.
(Enlarge Image)
Figure 1.
Cumulative event-free survival (Kaplan–Meier analysis) of death, myocardial infarction, and ischaemia-driven target vessel revascularization at complete follow-up in the three study groups. Prednisone and drug-eluting stents groups show significantly higher event-free survival compared with bare metal stents patients.
Differences in terms of MACE and its landmark analysis (30 days, 1 year, between 1 and 4 years, and up to 4 years) are shown in Table 2 and Table 3. Mortality at 4 years was similar among the three groups and all cases were attributed a possible cardiovascular nature.
Spontaneous MI related to the target vessel within 1 year occurred in two patients of the BMS group (due to subacute stent thrombosis in one case, and due to occlusive restenosis in the second). At long term, three DES patients had spontaneous MI due to very late (definite) stent thrombosis. A possible stent thrombosis was adjudicated as a cause of sudden death in one DES patient (Table 3). All these events occurred under single anti-platelet regimen and had no correlation with recent therapeutic changes.
The need for TVR at long-term remained higher in the BMS group (23.2%), compared with prednisone (13.6%), or to DES (15.2%), although these differences did not attain statistical significance. Non-TVR rates in the prednisone group were 4.8%, compared with 7.2% in the BMS and 12% in the DES group, and the need for new revascularizations in other than the index sites (i.e. non-TLR plus non-TVR) was 9.6% in the prednisone group, compared with BMS (16.8%) or DES (20.8%).
The occurrence of newly diagnosed diabetes, peptic ulcer, refractory hypertension, auto-immune disease or cancer in the three groups was clinically irrelevant and homogeneously distributed.
At univariate analysis generic variables associated with the occurrence of MACE were baseline levels of creatinine (HR: 2.89, 95% CI: 0.96–8.69, P = 0.05), smoking habit (HR: 1.67, 95% CI: 1.05–2.66, P = 0.03), the presence of triple-vessel disease (HR: 1.53, 95% CI: 1.13–2.08, P = 0.005), the length (HR: 1.05, 95% CI: 1.00–1.01, P = 0.02), and the diameter of the stents (HR: 0.42, 95% CI: 0.25–0.67, P = 0.001). In the multivariate model, all the same variables, except the baseline creatinine levels, emerged as independent predictors on MACE. Treatment with prednisone significantly reduced the HR for the occurrence of MACE compared with BMS (HR = 0.447, 95% CI: 0.29–0.80, P = 0.007). The treatment with DES compared with BMS yielded an HR of 0.519 with a 95% CI: 0.29–0.97 and P = 0.05.
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