We performed a study-level meta-analysis to provide more robust evidence on safety of very low LDL-cholesterol (LDL-C) levels. Concerns on the safety of LDL-C values achieved with potent lipid-lowering therapies have been raised. We searched randomized trials reporting clinical outcomes with intensive lipid-lowering treatments leading to very low (<40 mg/dL) LDL-C levels vs a control group with higher LDL-C levels. Only studies with follow-up duration ≥ 3 months were considered. Primary endpoint was the incidence of various safety measures. A total of 10 randomized trials were overall included, with 38 427 patients being in the very low LDL-C group vs 70 668 in the control group. Median follow-up duration was 28.8 months. The incidence of all safety outcomes was similar in the two groups: cardiovascular death: OR 1.13, 95% CI 0.87–1.45; P = 0.36; any adverse events: OR 1.00, 0.90–1.11, P = 0.94; adverse events leading to drug discontinuation: OR 1.00, 0.87–1.15, P = 0.99; cancer: OR 1.02, 0.95–1.10, P = 0.57; haemorrhagic stroke OR 0.89, 0.66–1.20, P = 0.44; new-onset diabetes: OR 1.16, 0.91–1.47, P = 0.23; neurocognitive disorders: OR 0.97, 0.91–1.04, P = 0.41; haepatobiliary disorders: OR 0.99, 0.83–1.18, P = 0.93; muscle disorders: OR 0.94, 0.77–1.13, P = 0.49; cataract: OR 1.28, 0.78–2.10, P = 0.34. The rates of major adverse cardiovascular events were significantly lower in the very low LDL-C group: OR 0.82, 0.72–0.94, P = 0.005. This meta-analysis indicates that very low LDL-C levels on intensive lipid-lowering treatments are not associated with any adverse event and maintain a persistent reduction of cardiovascular events.

Despite encouraging short-term and mid-term results, transcatheter aortic valve implantation (TAVI) interventions are still burdened from high rates of adverse events, stressing the need for accurate predictive risk instruments. We compared available surgical risk scores to describe unfavorable outcomes after TAVI. The Age, Creatinine, and Ejection fraction (ACEF) score, the logistic Euroscore, and the Society of Thoracic Surgeons Mortality score (STS) were appraised for their independent power of prediction and for their accuracy (C-index) to predict 30-day and medium-term mortality, according to the Valve Academic Research Consortium. Nine hundred and sixty-two patients were included. All the scores demonstrated a moderate positive correlation. The closest correlation was observed between the STS score and Euroscore. After logistic regression analysis, STS score and Logistic Euroscore provided independent prediction for short-term all-cause mortality [P = 0.02, odds ratio (OR) 1.1; 95% confidence interval (CI) 1.06–1.31 and P = 0.027, OR 1.03; 95% CI 1.01–1.405]. For in-hospital complications, only STS score performed significantly (P = 0.005, OR 1.05; 95% CI 1.01–1.06). ACEF, Euroscore, and STS score showed low accuracy for 30-day all-cause mortality (area under the curve 0.6, 0.44–0.75; vs. 0.53, 0.42–0.61; vs. 0.62, 0.52–0.71, respectively), whereas STS score performed better for in-hospital complications (0.59, 0.55–0.64). Moreover, after Cox-multivariate adjustments, only ACEF score was near to significance to predict all-cause mortality at mid-term (OR 1.7; 0.8–2.9; P = 0.058), showing the highest accuracy (0.63, 0.55–0.71). In TAVI patients, ACEF score, STS score and Logistic Euroscore provided only a moderate correlation and a low accuracy both for 30-day and medium-term outcomes. Dedicated scores are needed to properly tailor time and kind of approach.