HMG-CoA reductase inhibitors ('statins') represent the most effective and widely prescribed drugs currently available for the reduction of low-density lipoprotein cholesterol, a critical therapeutic ...target for primary and secondary prevention of cardiovascular atherosclerotic disease. In the face of the established lipid lowering and the emerging pleiotropic properties of statins, the patient population suitable for long-term statin treatment is expected to further expand. An overall positive safety and tolerability profile of statins has been established, although adverse events have been reported. Skeletal muscle-related events are the most common adverse events of statin treatment. Statin-induced myopathy can (rarely) manifest with severe and potentially fatal cases of rhabdomyolysis, thus rendering the identification of the underlying predisposing factors critical. The purpose of this review is to summarize the factors that increase the risk of statin-related myopathy. Data from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects were reviewed. Briefly, the epidemiology, clinical spectrum and molecular mechanisms of statin-associated myopathy are discussed. We further analyse in detail the risk factors that precipitate or increase the likelihood of statin-related myopathy. Individual demographic features, genetic factors and co-morbidities that may account for the significant interindividual variability in the myopathic risk are presented. Physicochemical properties of statins have been implicated in the differential risk of currently marketed statins. Pharmacokinetic interactions with concomitant medications that interfere with statin metabolism and alter their systemic bioavailability are reviewed. Of particular clinical interest in cases of resistant dyslipidaemia is the interaction of statins with other classes of lipid-lowering agents; current data on the relative safety of available combinations are summarized. Finally, we provide an update of current guidelines for the prevention and management of statin myopathy. The identification of patients with an increased proclivity to statin-induced myopathy could allow more cost-effective approaches of monitoring and screening, facilitate targeted prevention of potential complications, and further improve the already overwhelmingly positive benefit-risk ratio of statins.
Clinical trials with PCSK9 inhibitors have shown a robust decrease in plasma LDL levels and a significant reduction in the incidence of cardiovascular atherosclerotic events. However, the role of ...PCSK9 in atherosclerosis is not well investigated and it remains unclear whether PCSK9 inhibition has direct, LDL-independent, anti-atherosclerotic effects. This review outlines the molecular pathways and targets of PCSK9 in atherosclerosis and summarizes the experimental and clinical data supporting the anti-atherosclerotic (pleiotropic) actions of PCSK9 inhibitors.
PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g., endothelial cell, smooth muscle cell, and macrophage) and is detected inside human atherosclerotic plaque. Preclinical studies have shown that inhibition of PCSK9 can attenuate atherogenesis and plaque inflammation. Besides increasing plasma LDL, PCSK9 appears to promote the initiation and progression of atherosclerosis. Inhibition of PCSK9 may confer atheroprotection that extends beyond its lipid-lowering effects.
In patients with stable coronary artery disease, percutaneous coronary intervention is associated with improved outcomes if the lesion is deemed significant by invasive functional assessment using ...fractional flow reserve. Recent studies have shown that a revascularization strategy using instantaneous wave-free ratio is noninferior to fractional flow reserve in patients with intermediate-grade stenoses. The decision to perform coronary artery bypass grafting surgery is usually based on anatomic assessment of stenosis severity by coronary angiography. The data on the role of invasive functional assessment in guiding surgical revascularization are limited. In this review, we discuss the diagnostic and prognostic significance of invasive functional assessment in patients considered for coronary artery bypass grafting. In addition, we critically discuss ongoing and future clinical trials on the role of invasive functional assessment in surgical revascularization.
Abstract Background Geometrically-correct 3D OCT is a new imaging modality with the potential to investigate the association of local hemodynamic microenvironment with OCT-derived high-risk features. ...We aimed to describe the methodology of 3D OCT and investigate the accuracy, inter- and intra-observer agreement of 3D OCT in reconstructing coronary arteries and calculating ESS, using 3D IVUS and 3D QCA as references. Methods-Results 35 coronary artery segments derived from 30 patients were reconstructed in 3D space using 3D OCT. 3D OCT was validated against 3D IVUS and 3D QCA. The agreement in artery reconstruction among 3D OCT, 3D IVUS and 3D QCA was assessed in 3-mm-long subsegments using lumen morphometry and ESS parameters. The inter- and intra-observer agreement of 3D OCT, 3D IVUS and 3D QCA were assessed in a representative sample of 61 subsegments (n = 5 arteries). The data processing times for each reconstruction methodology were also calculated. There was a very high agreement between 3D OCT vs. 3D IVUS and 3D OCT vs. 3D QCA in terms of total reconstructed artery length and volume, as well as in terms of segmental morphometric and ESS metrics with mean differences close to zero and narrow limits of agreement (Bland–Altman analysis). 3D OCT exhibited excellent inter- and intra-observer agreement. The analysis time with 3D OCT was significantly lower compared to 3D IVUS. Conclusions Geometrically-correct 3D OCT is a feasible, accurate and reproducible 3D reconstruction technique that can perform reliable ESS calculations in coronary arteries.
Although stenting of non-branched arterial segments has acceptable clinical outcomes, in-stent restenosis (ISR) and stent thrombosis remain clinically significant issues for vascular bifurcations ...(15-28% restenosis). Local fluid and solid stresses appear to play an important role in restenosis and thrombosis. The combined role of wall shear stress (WSS) and circumferential wall stresses (CWS) is unclear in the case of stenting at vascular bifurcations. Using numerical simulations, we computed the fluid shear, solid stresses and the stress ratio at the the bifurcation region. Stenting of main vessel increased the maximum CWS in the the side branch (SB), resulting in a nearly two-fold increase of stress ratio in the SB compared to the MB (5.1 × 10
vs. 9.2 × 10
). The existence of plaque decreased WSS and increased CWS near the carina, increasing the stress ratio at the SB. The changes of stress ratio were highly consistent with clinical data on bifurcation stenting. Fluid dynamics and solids mechanics should be considered in planning of stenting for a specific bifurcation, as their combined biomechanical effect may play an important role in stent restenosis and thrombosis.
Whether prolonged dual antiplatelet therapy (DAPT) is more protective in patients with CKD and drug-eluting stents compared with shorter DAPT is uncertain. The purpose of this meta-analysis was to ...examine whether shorter DAPT in patients with drug-eluting stents and CKD is associated with lower mortality or major adverse cardiovascular event rates compared with longer DAPT.
A Medline literature research was conducted to identify randomized trials in patients with drug-eluting stents comparing different DAPT duration strategies. Inclusion of patients with CKD was also required. The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or stent thrombosis (definite or probable). Major bleeding was the secondary outcome. The risk ratio (RR) was estimated using a random-effects model.
Five randomized trials were included (1902 patients with CKD). Short DAPT (≤6 months) was associated with a similar incidence of the primary outcome, compared with 12-month DAPT among patients with CKD (48 versus 50 events; RR, 0.93; 95% confidence interval 95% CI, 0.64 to 1.36;
=0.72). Twelve-month DAPT was also associated with a similar incidence of the primary outcome compared with extended DAPT (≥30 months) in the CKD subgroup (35 versus 35 events; RR, 1.04; 95% CI, 0.67 to 1.62;
=0.87). Numerically lower major bleeding event rates were detected with shorter versus 12-month DAPT (9 versus 13 events; RR, 0.69; 95% CI, 0.30 to 1.60;
=0.39) and 12-month versus extended DAPT (9 versus 12 events; RR, 0.83; 95% CI, 0.35 to 1.93;
=0.66) in patients with CKD.
Short DAPT does not appear to be inferior to longer DAPT in patients with CKD and drug-eluting stents. Because of imprecision in estimates (few events and wide confidence intervals), no definite conclusions can be drawn with respect to stent thrombosis.
Introduction: Acute right ventricular myocardial infarction (RVMI) is observed in 30-50% of patients presenting with inferior wall myocardial infarction (MI) and, occasionally, with anterior wall MI. ...The clinical consequences vary from no hemodynamic compromise to severe hypotension and cardiogenic shock depending on the extent of RV ischemia.
Areas covered: The pathophysiological mechanisms, diagnostic steps, and novel therapeutic approaches of acute RVMI are described.
Expert commentary: Diagnosis of acute RVMI is based on physical examination, cardiac biomarkers, electrocardiography, and coronary angiography, whereas noninvasive imaging modalities (echocardiography, cardiac magnetic resonance imaging) play a complementary role. Early revascularization, percutaneous or pharmacological, represents key step in the management of RMVI. Maintenance of reasonable heart rate and atrioventricular synchrony is essential to sustain adequate cardiac output in these patients. When conventional treatment is not successful, mechanical circulatory support, including right ventricle assist devices, percutaneous cardiopulmonary support, and intra-aortic balloon pump, might be considered. The prognosis associated with RVMI is worse in the short term, compared to non-RVMI, but those patients who survive hospitalization have a relatively good long-term prognosis.
PDF
