After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low-dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard-dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3-year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy-proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor-specific HLA-antibodies remained similar in both groups. Low-dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.
Patients’ prognostication around cardiac surgery is key to better assess risk–benefit balance. Preoperative brain natriuretic peptide (BNP) biomarker has been associated with mortality after cardiac surgery, but its added value with EuroScore 2 remains to be confirmed. In a prospective registry cohort of 4,980 patients undergoing cardiac surgery, the prognostic performance of EuroScore 2 and preoperative BNP was assessed regarding postoperative in-hospital mortality. Discrimination feature was evaluated using receiver-operator-characteristics analysis with area under curve (AUROC). Calibration feature was assessed using Hosmer–Lemeshow test. Multivariable analysis was performed to assess the association between covariates and in-hospital mortality. In-hospital mortality was 3.7%. The AUROC of EuroScore 2 was 0.82 (95% confidence interval (95%CI) 0.79–0.85, p < 0.0001). The AUROC of BNP was 0.66 (95%CI 0.62–0.70, p < 0.0001). The combined model with an AUROC of 0.67 (95%CI 0.63–0.71, p = 0.0001) did not yield better AUROC than EuroScore 2 alone (p < 0.0001 in disfavor of the combined model), nor BNP alone (p = 0.79). In multivariable analysis, EuroScore 2 remained independently associated with mortality (adj.OR of 1.12 (1.10–1.14), p < 0.0001), but BNP was not. Preoperative BNP was not an independent risk factor of postoperative mortality and did not add prognostic information, as compared to EuroScore 2 alone.Clinical trial registry Registry for the Improvement of Postoperative OutcomeS in Cardiac and Thoracic surgEry (RIPOSTE) database (NCT03209674).
Background Inhibition of the interleukin-1β (IL-1β) innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high sensitivity C-reactive protein (hs-CRP). However, the prognosis value of IL-1β level in acute myocardial infarction patients has never been evaluated. We aim to assess the association between IL-1β level with all-cause mortality in patients with acute ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death. Methods IL-1β concentration was measured among 1398 STEMI patients enrolled in a prospective cohort study. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90-days and one-year using a multivariate-cox proportional regression analysis. Major cardiovascular events (MACE) were also analyzed. Results In a STEMI population, IL-1β concentration measured at admission was independently associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR], 1.43 per 1SD increase; 95% CI, 1.12 to 1.83; p<0.005). The relation was nonlinear, and we identified a threshold of IL-1β >10 pg/mL that was markedly associated with higher mortality rates at 90 days (adjHR: 2.80; 95% CI: 1.63–4.80, p=0.0002) and one-year (adjHR: 1.75; 95% CI: 1.09–2.78, p=0.019), regardless of the hs-CRP concentration. The relationship was even stronger when considering cardiovascular mortality and MACE at 90 days (adjHR: 2.31; 95% CI: 1.30–4.10, p=0.004 and 2.17; 95% CI: 1.24–3.80, p=0.006) and at one year (adjHR: 2.26; 95% CI: 1.31–3.87, p=0.03 and 2.25; 95% CI: 1.33–3.79, p=0.004). Conclusion IL-1β measured at admission in acute MI patients is associated with the risk of mortality and recurrent major cardiovascular events, regardless of the CRP level. A threshold of 10 pg/mL identifies patients at higher risk of events. Survival Funding Acknowledgement Type of funding source: None
Background Some data suggest that low levels of low-density lipoprotein cholesterol (LDL-C) are associated with risk of cataracts. Proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors reduce LDL-C below levels achieved with statins alone. We determined whether the incidence of cataracts was influenced by treatment with the PCSK9 inhibitor alirocumab versus placebo, and whether that incidence was affected by achieved LDL-C levels. Methods The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome receiving high-intensity or maximum-tolerated statin. Incident cataracts were pre-specified events of interest. In multivariable analysis using propensity score-matching on characteristics including cataract risk factors, incident cataracts were compared in the alirocumab and placebo groups according to LDL-C levels achieved with alirocumab. Results Over median follow-up of 2.8 years (interquartile range 2.3 − 3.4), the incidence of cataracts was similar with alirocumab (127/9462 [1.3%]) versus placebo (134/9462 [1.4%]); hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74 − 1.20). In patients treated with alirocumab with ≥ 2 LDL-C values < 25 mg/dL (0.65 mmol/L), the incidence of cataracts was 71/4305 (1.6%), versus 60/4305 (1.4%) in propensity score-matched patients from the placebo group (HR 1.10, CI 95% 0.78 − 1.55). In patients treated with alirocumab with ≥ 2 LDL-C values < 15 mg/dL (0.39 mmol/L), the incidence of cataracts was 13/782 (1.7%), versus 36/2346 (1.5%) in matched patients from the placebo group (HR 1.03, CI 95% 0.54 − 1.94). Conclusion Treatment with alirocumab versus placebo, added to statin, did not influence the incidence of cataracts, even when achieved LDL-C levels on alirocumab were very low. Longer follow-up studies might be necessary to exclude the long-term effects on the incidence or progression of cataracts. Trial registration ClinicalTrials.gov Identifier: NCT01663402.
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