Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence.

PURPOSE: We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS). METHODS: This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type. RESULTS: A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41-0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46-0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67-1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48-0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34-0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome. CONCLUSION: A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.

Role of Matrix Gla Protein in the Complex Network of Coronary Artery Disease: A Comprehensive Review.

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather than passively, as previously regarded. Matrix Gla protein (MGP), a vitamin K-dependent protein, emerged as an important inhibitor of both intimal and medial vascular calcification. The functionality of MGP hinges on two post-translational modifications: phosphorylation and carboxylation. Depending on the above-noted modifications, various species of MGP may exist in circulation, each with their respective level of functionality. Emerging data suggest that dysfunctional species of MGP, markedly, dephosphorylated-uncarboxylated MGP, might find its application as biomarkers of microvascular health, and assist in clinical decision making with regard to initiation of vitamin K supplementation. Hence, in this review we summarized the current knowledge with respect to the role of MGP in the complex network of vascular calcification with concurrent inferences to CAD. In addition, we discussed the effects of warfarin use on MGP functionality, with concomitant implications to coronary plaque stability.

Transient neurological symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics in adult surgical patients: a network meta-analysis.

BACKGROUND: Spinal anaesthesia has been implicated as one of the possible causes of neurological complications following surgical procedures. This painful condition, occurring during the immediate postoperative period, is termed transient neurological symptoms (TNS) and is typically observed after the use of spinal lidocaine. Alternatives to lidocaine that can provide high-quality anaesthesia without TNS development are needed. This review was originally published in 2005, and last updated in 2009. OBJECTIVES: To determine the frequency of TNS after spinal anaesthesia with lidocaine and compare it with other types of local anaesthetics by performing a meta-analysis for all pair-wise comparisons, and conducting network meta-analysis (NMA) to rank interventions. SEARCH METHODS: We searched CENTRAL, MEDLINE, Elsevier Embase, and LILACS on 25 November 2018. We searched clinical trial registries and handsearched the reference lists of trials and review articles. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing the frequency of TNS after spinal anaesthesia with lidocaine to other local anaesthetics. Studies had to have two or more arms that used distinct local anaesthetics (irrespective of the concentration and baricity of the solution) for spinal anaesthesia in preparation for surgery. We included adults who received spinal anaesthesia and considered all pregnant participants as a subgroup. The follow-up period for TNS was at least 24 hours. DATA COLLECTION AND ANALYSIS: Four review authors independently assessed studies for inclusion. Three review authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. We performed meta-analysis for all pair-wise comparisons of local anaesthetics, as well as NMA. We used an inverse variance weighting for summary statistics and a random-effects model as we expected methodological and clinical heterogeneity across the included studies resulting in varying effect sizes between studies of pair-wise comparisons. The NMA used all included studies based on a graph theoretical approach within a frequentist framework. Finally, we ranked the competing treatments by P scores. MAIN RESULTS: The analysis included 24 trials reporting on 2226 participants of whom 239 developed TNS. Two studies are awaiting classification and one is ongoing. Included studies mostly had unclear to high risk of bias. The NMA included 24 studies and eight different local anaesthetics; the number of pair-wise comparisons was 32 and the number of different pair-wise comparisons was 11. This analysis showed that, compared to lidocaine, the risk ratio (RR) of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine with RRs in the range of 0.10 to 0.23 while 2-chloroprocaine and mepivacaine did not differ in terms of RR of TNS development compared to lidocaine. Pair-wise meta-analysis showed that compared with lidocaine, most local anaesthetics were associated with a reduced risk of TNS development (except 2-chloroprocaine and mepivacaine) (bupivacaine: RR 0.16, 95% confidence interval (CI) 0.09 to 0.28; 12 studies; moderate-quality evidence; 2-chloroprocaine: RR 0.09, 95% CI 0.01 to 1.51; 2 studies; low-quality evidence; levobupivacaine: RR 0.13, 95% CI 0.02 to 0.69; 2 studies; low-quality evidence; mepivacaine: RR 1.01, 95% CI 0.18 to 5.82; 4 studies; very low-quality evidence; prilocaine: RR 0.18, 95% CI 0.07 to 0.49; 4 studies; moderate-quality evidence; procaine: RR 0.14, 95% CI 0.04 to 0.52; 2 studies; moderate-quality evidence; ropivacaine: RR 0.10, 95% CI 0.01 to 0.78; 2 studies; low-quality evidence). We were unable to perform any of our planned subgroup analyses due to the low number of TNS events. AUTHORS' CONCLUSIONS: Results from both NMA and pair-wise meta-analysis indicate that the risk of developing TNS after spinal anaesthesia is lower when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine are used compared to lidocaine. The use of 2-chloroprocaine and mepivacaine had a similar risk to lidocaine in terms of TNS development after spinal anaesthesia. Patients should be informed of TNS as a possible adverse effect of local anaesthesia with lidocaine and the choice of anaesthetic agent should be based on the specific clinical context and parameters such as the expected duration of the procedure and the quality of anaesthesia. Due to the very low- to moderate-quality evidence (GRADE), future research efforts in this field are required to assess alternatives to lidocaine that would be able to provide high-quality anaesthesia without TNS development. The two studies awaiting classification and one ongoing study may alter the conclusions of the review once assessed.