Fenofibrate/simvastatin fixed-dose combination in the treatment of mixed dyslipidemia: safety, efficacy, and place in therapy.

Lipids disorder is the principal cause of atherosclerosis and may present with several forms, according to blood lipoprotein prevalence. One of the most common forms is combined dyslipidemia, characterized by high levels of triglycerides and low level of high-density lipoprotein. Single lipid-lowering drugs may have very selective effect on lipoproteins; hence, the need to use multiple therapy against dyslipidemia. However, the risk of toxicity is a concerning issue. In this review, the effect and safety of an approved combination therapy with simvastatin plus fenofibrate are described, with an analysis of pros and cons resulting from randomized multicenter trials, meta-analyses, animal models, and case reports as well.

Bioresorbable coronary stent for the treatment of complex coronary lesions: Data from an all-comer registry.

BACKGROUND: The study aimed to report the results from an all-comers registry of patients undergoing coronary angioplasty and treated with bioresorbable vascular scaffold (BVS). METHODS: Fifty-five consecutive patients with type B/C coronary lesions according to the AHA classification and treated with BVS were enrolled in the study. The clinical and procedural characteristics of enrolled patients were recorded. Fifty-five consecutive subjects with coronary lesions type B/C treated with everolimus eluting stent (EES) were used as control group. RESULTS: The incidence of adverse events was not statistically significant comparing subjects treated with BVS with those treated with EES. Non significant differences were also found in the follow-up considering the presence of diabetes, multivessel disease, use of more than one stent at the same time, diagnosis (STEMI vs UA/NSTEMI), use of coronary stents in overlapping. The differences were significant considering the type of lesion (Log-Rank p<0.05), stenoses treated in correspondence of a coronary bifurcation (p<0.05), the SYNTAX score (cut off 22) (p<0.001); after multivariable correction for age and gender, however, differences remained significant only for SYNTAX score. CONCLUSIONS: The use of BVS in an all-comers registry of patients undergoing coronary angioplasty on complex coronary lesions is associated with a safety profile comparable to that obtained with EES; the use of BVS in particular conditions, such as very high SYNTAX score, should be further assessed.

Pre-hospital electrocardiogram triage with telemedicine near halves time to treatment in STEMI: A meta-analysis and meta-regression analysis of non-randomized studies.

BACKGROUND: A shorter time to treatment has been shown to be associated with lower mortality rates in acute myocardial infarction (AMI). Several strategies have been adopted with the aim to reduce any delay in diagnosis of AMI: pre-hospital triage with telemedicine is one of such strategies. We therefore aimed to measure the real effect of pre-hospital triage with telemedicine in case of AMI in a meta-analysis study. METHODS: We performed a meta-analysis of non-randomized studies with the aim to quantify the exact reduction of time to treatment achieved by pre-hospital triage with telemedicine. Data were pooled and compared by relative time reduction and 95% C.I.s. A meta-regression analysis was performed in order to find possible predictors of shorter time to treatment. RESULTS: Eleven studies were selected and finally evaluated in the study. The overall relative reduction of time to treatment with pre-hospital triage and telemedicine was -38/-40% (p<0.001). Absolute time reduction was significantly correlated to time to treatment in the control groups (p<0.001), while relative time reduction was independent. A non-significant trend toward shorter relative time reductions was observed over years. CONCLUSIONS: Pre-hospital triage with telemedicine is associated with a near halved time to treatment in AMI. The benefit is larger in terms of absolute time to treatment reduction in populations with larger delays to treatment.

Direct oral anti-coagulants compared with vitamin-K inhibitors and low-molecular-weight-heparin for the prevention of venous thromboembolism in patients with cancer: A meta-analysis study.

BACKGROUND: Prior meta-analysis studies showed that direct oral anticoagulants (DOAs) are as effective and safe as warfarin for the prevention of recurrences in patients with venous thrombo-embolism(VTE) and cancer. However, randomized studies also showed that low-molecular-weight-heparin (LMWH) performs better than warfarin in subjects with cancer. We therefore aimed to assess whether, even after pooling data with warfarin and LMWH, the use of DOAs remains safe and effective. METHODS: We performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer. Data on recurrent VTE and major and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs. RESULTS: Nine studies were included in the meta-analysis, seven in comparison with VKI, 2 with LMWH, accounting for a total of 1952 patients. VTE recurred in 5.4% and in 5.9% of patients with cancer treated with DOAs and conventional treatment, respectively (OR 0.79; 95% CI, 0.53-1.17; I2 0%). Bleeding occurred in 10.8% and 11% of patients receiving DOAs and conventional treatment, respectively (OR 0.96; 95% CI, 0.71-1.30; I2, 44%). Higher bleeding rates were found when DOAs are compared with LMWH (OR 2.72, 95% CI, 1.05-7.01). CONCLUSIONS: DOAs seem to be as effective and safe as conventional treatment for the prevention of VTE in patients with cancer in comparison with VKI. Higher bleeding rates were found when DOAs are compared with LMWH.

Therapy of stress (takotsubo) cardiomyopathy: present shortcomings and future perspectives.

Several therapeutic options are available for the treatment of the acute phase of stress cardiomyopathy, pharmacological (ß-blockers, diuretics, anticoagulants, antiarrhythmics, noncatecholamine inotropics [levosimendan]), and nonpharmacological (intra-aortic balloon pumping, extracorporeal membrane oxygenation), according to the wide possible clinical presentation and course of the disease. However, there is a gap in evidence, and very few data come from randomized and adequately powered studies. Some evidence supports the use of ß-blockers, in particular with a short half-life, in the case of left ventricular outflow tract obstruction, and angiotensin-converting enzyme inhibitors in secondary prevention. Future perspectives include the study of genetic basis of stress cardiomyopathy, role of miRNA and neurovegetative modulation. Randomized studies, however, are surely warranted.

Catecholaminergic polymorphic ventricular tachycardia associated with sinus node dysfunction and junctional rhythm: Case report and literature review.

We report the case of a 38-year-old woman with history of syncope and polymorphic ventricular tachycardia; tachycardia was inducible at exercise stress test, not at electrophysiologic study. Phases of QT prolongation were found at ambulatory electrocardiogram monitoring. The woman came to our attention for periodic control of implantable loop recorder. Rest electrocardiogram at admission unexpectedly showed sinus bradycardia, junctional rhythm, and ventricular premature beats. Furthermore, loop recorder control revealed a short run of bidirectional tachycardia, not associated with syncope. Final diagnosis was catecholaminergic polymorphic ventricular tachycardia, and the patient was implanted with an ICD. We therefore report an unusual case of bidirectional ventricular tachycardia associated with sinus node dysfunction and junctional escape rhythm. We hypothesize that a diffuse dysfunction of cardiac conduction system, presumably based on diffuse disorder of calcium handling, may be responsible for both sinus node failure and ventricular tachycardia.

Drug treatment rates with beta-blockers and ACE-inhibitors/angiotensin receptor blockers and recurrences in takotsubo cardiomyopathy: A meta-regression analysis.

BACKGROUND: In a recent paper Singh et al. analyzed the effect of drug treatment on recurrence of takotsubo cardiomyopathy (TTC) in a comprehensive meta-analysis. The study found that recurrence rates were independent of clinic utilization of BB prescription, but inversely correlated with ACEi/ARB prescription: authors therefore conclude that ACEi/ARB rather than BB may reduce risk of recurrence. METHODS: We aimed to re-analyze data reported in the study, now weighted for populations' size, in a meta-regression analysis. RESULTS: After multiple meta-regression analysis, we found a significant regression between rates of prescription of ACEi and rates of recurrence of TTC; regression was not statistically significant for BBs. CONCLUSIONS: On the bases of our re-analysis, we confirm that rates of recurrence of TTC are lower in populations of patients with higher rates of treatment with ACEi/ARB. That could not necessarily imply that ACEi may prevent recurrence of TTC, but barely that, for example, rates of recurrence are lower in cohorts more compliant with therapy or more prescribed with ACEi because more carefully followed. Randomized prospective studies are surely warranted.

Inferior ST-Elevation Acute Myocardial Infarction or an Inferior-Lead Brugada-like Electrocardiogram Pattern Associated With the Use of Pregabalin and Quetiapine?

The Brugada electrocardiogram pattern is characterized by coved-type ST-elevation (>2 mm) in the right precordial leads. We report the case of a 62-year-old man, with bipolar disorder, admitted to the emergency department because of dyspnea and chest discomfort. The patient was on treatment with pregabalin and quetiapine. Unexpectedly, electrocardiogram at admission showed diffuse ST-elevation, more evident in inferior leads, where a Brugada-like pattern was present. The patient underwent coronary angiography with a diagnosis of suspected acute coronary syndrome. Coronary angiography, however, showed mild coronary artery disease not requiring coronary angioplasty. Echocardiography did not reveal left ventricular dysfunction or pericardial effusion. Troponin levels remained normal over serial controls. Eventually, chest radiography showed lung opacities and consolidation suggestive for pneumonia. To the best of our knowledge, this is one of the first cases showing a transient Brugada-like electrocardiogram pattern in inferior leads, probably amplified by the administration of pregabalin and quetiapine.

Bioresorbable vascular scaffolds: design, clinical trials, and current applications.

In recent years, bioresorbable vascular scaffolds (BVS) have been introduced into clinical practice. The main advantage of BVS is that they overcome the problem of the foreign body in the treated artery. BVS, once placed into narrowed coronary vessels, behave like a conventional drug-eluting stent, but a device that disappears over time can preserve the anatomy and physiology of the treated vessel. The progression of stenosis after stenting has been attributed, at least in part, to inflammation around metallic struts, that, however, disappears gradually when using BVS. BVS have proven to be effective and safe as drug-eluting stents; in fact, the rate of adverse cardiovascular events and scaffold thrombosis in patients is low. The aim of this review article is to provide a comprehensive and updated description of the status of the art on BVS, highlighting the current evidence and future perspectives of this technology.

Early inflammatory cytokine response: a direct comparison between spontaneous coronary plaque destabilization vs angioplasty induced.

AIM: To compare inflammatory response accompanying acute coronary syndrome (ACS) with that following coronary plaque rupture caused by coronary angioplasty (PCI). METHODS: Twenty-seven consecutive subjects with either ACS or treated with PCI in the subacute phase of ACS underwent serial evaluation of circulating interleukin (IL)-2, IL-8, IL-10, interferon (IFN)-γ and tumor-necrosis-factor (TNF)-α levels. Blood samples were drawn immediately before angioplasty (T0) in the PCI group or at admission in the ACS group, 12 h (T1) and 24 h later (T2). RESULTS: Differences between cytokine levels were substantially not statistically significant when comparing PCI, non-ST-elevation-ACS, and ST-elevation-ACS groups, especially 24 h after plaque rupture (T2, Type-II error 85-94%). CONCLUSIONS: Inflammatory activation during the first 24 h of ACS or after PCI is comparable, regardless of myocardial damage in terms of troponin levels. Coronary plaque rupture may be presumed as being the main responsible for increased circulating cytokine levels in this early phase.

Coronary artery ectasia is related to coronary slow flow and inflammatory activation.

AIM: To evaluate possible links between coronary flow anomalies, inflammatory activation and coronary artery ectasia (CAE). METHODS: Fourteen consecutive patients with CAE diagnosed at coronary angiography were enrolled in the study and compared with 17 patients with coronary atherosclerosis without CAE and 15 controls with normal coronary angiography. All patients underwent blood assay with evaluation of circulating levels of interleukin (IL)-1b, IL-2, IL-8, IL-10 and tumor-necrosis-factor(TNF)-α. The number of coronary segments showing CAE at coronary angiography, the Markis class, and coronary flow assessed with TIMI frame count (TFC) were also assessed. RESULTS: Subjects with CAE showed higher levels of IL-1b, TNF-α, and IL-10 (p<0.05). The number of coronary segments showing CAE was related to TFC both in left anterior descending (LAD) coronary artery (p<0.01) and in right coronary artery (RCA) (p<0.001), and to circulating levels of IL-1b and IL-10 (p<0.01). TFC on LAD (p<0.05) and on RCA (p<0.001), circulating IL-1b levels (p<0.01), IL-8 (p<0.05), and IL-10 (p<0.01) were proportionally increased comparing controls, subjects with coronary atherosclerosis without CAE, and with decreasing Markis class. In subjects with CAE involving LAD, TFC on LAD was related to IL-8 and TNF-α levels (p<0.05); subjects with IL-1b levels above median showed higher TFC values on LAD (p<0.01), CONCLUSIONS: In subjects with CAE, the extension of disease is related to the impairment of coronary circulation and to inflammatory activation. The inflammatory response is also related to an impaired coronary circulation.

Recurrent angina after coronary angioplasty: mechanisms, diagnostic and therapeutic options.

Recurrent angina in patients who underwent percutaneous coronary intervention is defined as recurrence of chest pain or chest discomfort. Careful assessment is recommended to differentiate between non-cardiac and cardiac causes. In the case of the latter, recurrent angina occurrence can be related to structural ('stretch pain', in-stent restenosis, in-stent thrombosis, incomplete revascularization, progression of coronary atherosclerosis) or functional (coronary micro-vascular dysfunction, epicardial coronary spasm) causes. Even though a complete diagnostic algorithm has not been validated, ECG exercise testing, stress imaging and invasive assessment of coronary blood flow and coronary vaso-motion (i.e. coronary flow reserve, provocation testing for coronary spasm) may be required. When repeated coronary revascularization is not indicated, therapeutic approaches should aim at targeting the underlying mechanism for the patient's symptoms using a variety of drugs currently available such as beta-blockers, calcium-channel blockers, ivabradine or ranolazine.

Direct renin inhibition: update on clinical investigations with aliskiren.

The renin­angiotensin­aldosterone system (RAAS) plays a pivotal role in regulating blood pressure, volume, and electrolytes. The final product of RAAS cascade is angiotensin II, which exerts diverse biological activities via binding to one of three known receptor types, with different binding consequences. Despite the success with conventional strategies to limit angiotensin II production and action, these agents promote a reflex rise in plasma renin activity, which is thought to be associated with an increased incidence of cardiovascular events. Several renin inhibitors have been synthesized in order to counteract deleterious consequences of renin activity and RAAS activation; aliskiren is the first of these new non-peptide direct renin inhibitors to be approved for the treatment of hypertension. The paper reviews pharmacokinetics of aliskiren and its role in hypertension, with particular regard to those studies that compared clinical efficacy of aliskiren in comparison and in addition to other antihypertensive drug strategies.