Cardiovascular Drugs

Correction to: Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry The first author’s name which previously read.

Prasugrel and Ticagrelor: the Romulus and Remus of Antiplatelet Therapy?

The Efficacy and Safety of Aerosolized Iloprost in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis Abstract Background This systematic review and meta-analysis was conducted to investigate the efficacy and safety of the chronic administration of aerosolized iloprost for pulmonary arterial hypertension (PAH). Methods All the relevant studies were obtained from three databases, namely, PubMed, Web of Science and the Cochrane Library, from the inception of each database to June 1, 2018. In our study, chronic treatment was defined as a period lasting at least 3 months. The rate of each event was analyzed by SPSS as a percentage with 95% confidence intervals (CIs). For the meta-analysis, a randomized effect model or a fixed effect model was applied according to the results of the heterogeneity test. Results Ten studies were included in this study, with a total of 370 patients treated with inhaled iloprost, including 214 in five randomized controlled trials and 156 in five prospective clinical trials. Among the patients who received inhaled iloprost, there was a significant improvement in the 6-min walk distance (6MWD) in the short-medium and prolonged treatment groups. Notably, the functionality improved by at least 1 class in 48.7% of the treated patients. In all the pooled studies, the estimated 3-month, 6-month, 1-year and 2-year event-free survival rates were 96.6%, 92.3%, 62.6% and 39.6%, respectively. In addition, there were eight adverse drug responses. Conclusion In this systematic review and meta-analysis, inhaled iloprost has been shown to be a safe and well-tolerated agent for PAH in the first 3 months after diagnosis. If used for a prolonged period, aerosol iloprost monotherapy could contribute to an unsatisfactory improvement in vascular remodeling and even a decreased event-free survival rate.

Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry Abstract Background Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI). Objective Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population. Methods RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9 months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10 mg once daily or acetylsalicylic acid plus ticagrelor 90 mg twice daily. Mean duration of DAPT was 12.04 ± 3.4 months with prasugrel and 11.90 ± 4.1 months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS]. Results In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12 months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p = 0.001]; MACE: 5% vs. 8.1% [p =  0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3–5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12 months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT. Conclusions Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12 months. The nonrandomized design of the present research means further studies are required to support these findings.

Clinical Performance of Apixaban vs. Vitamin K Antagonists in Patients with Atrial Fibrillation Undergoing Direct Electrical Current Cardioversion: A Prospective Propensity Score-Matched Cohort Study Abstract Introduction Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. Objectives This study compared the long-term efficacy and safety of apixaban with that of uninterrupted vitamin K antagonist (VKA) therapy in patients with AF scheduled for transesophageal echocardiogram (TEE)-guided direct current cardioversion (DCC) from June 2014 to September 2016. Methods We enrolled consecutive patients with persistent nonvalvular AF scheduled to undergo DCC. Patients received apixaban 5 mg or 2.5 mg twice daily (bid) or VKA at therapeutic doses for at least 3 weeks before and 4 weeks after DCC. All patients underwent anamnestic, clinical, electrocardiographic, and echocardiographic evaluation at each follow-up visit and were followed-up for 12 months. The primary efficacy endpoint was the composite of stroke/transient ischemic attack and systemic embolism. The primary safety endpoint was major bleeding. Results After propensity score matching, comparative treatment groups comprised 182 (75.8%) patients receiving apixaban 5 mg bid and 182 receiving VKA. A low incidence of atrial thrombus (0.5%) at TEE was found in both groups. The acute cardioversion success rate was 86.1% in the apixaban group (156/181) and 83.9% in the VKA group (152/181). During the follow-up period, a similarly low incidence of thromboembolic events (1.1%) was reported in both groups; the bleeding safety profile tended to favor apixaban over VKA (1.1 vs. 1.6%; p = 0.3). Conclusions Newly initiated anticoagulation with apixaban in patients with nonvalvular AF scheduled for TEE-guided DCC seems to be as effective and safe as uninterrupted VKA therapy during 12 months of follow-up.

Rivaroxaban With or Without Aspirin for the Secondary Prevention of Cardiovascular Disease: Clinical Implications of the COMPASS Trial Abstract The COMPASS trial compared the impact of the selective direct factor Xa inhibitor, rivaroxaban, as monotherapy or in combination with aspirin on major adverse cardiovascular events (MACE) in patients with stable atherosclerotic disease. Patients treated with rivaroxaban 2.5 mg twice daily in combination with aspirin experienced fewer cardiovascular events but more bleeding complications than those who received aspirin monotherapy. In contrast, a higher dose of rivaroxaban (5 mg twice daily) and aspirin produced no clinical benefit and continued to be associated with greater bleeding rates than aspirin. Examining this study in the context of other trials of anticoagulant therapy in atherosclerotic vascular disease, this review attempts to place the role of very low-dose rivaroxaban in clinical context and highlights areas for future research.

Pharmacotherapy of Obesity: Limits and Perspectives Abstract Obesity is a severe worldwide epidemic. Obesity comorbidities, such as type 2 diabetes mellitus, hypertension, and atherosclerosis, are costly for patients and governments. The treatment of obesity involves several facets, including lifestyle changes, bariatric surgery, and pharmacotherapy. As changes in lifestyle require considerable patient commitment that is sometimes unachievable, and surgery is expensive and invasive, pharmacotherapy is the primary option for most patients. This review describes the pharmacotherapy currently available in the USA, Europe, and Brazil, focusing on its limitations. We then analyze the results from clinical trials of new drug candidates. Most drugs cause weight loss of < 4 kg compared with controls, and severe adverse effects have caused a number of drugs to be withdrawn from the market in several countries. Drugs under development have not shown more significant weight loss or reduced adverse effects. We conclude that a significant portion of obese patients have few treatment options because of the adverse effects and minimal weight loss associated with current pharmacotherapy. However, drugs currently under development appear unable to change this scenario in the near future. Thus, it is essential that new compounds are developed and new molecular targets studied so obesity can be efficiently treated in all patients in the future.

Effects of Rosuvastatin and Aspirin on Retinal Vascular Structures in Hypercholesterolemic Patients with Low-to-Moderate Risk of Coronary Artery Disease Abstract Introduction Atherosclerosis erodes large elastic arteries and damages peripheral small vessels. Evaluating retinal vessel caliber enables exploration of the effect of improving microcirculation with statins. Objective We investigated whether rosuvastatin therapy improves retinal vasculature in hypercholesterolemic patients with a low-to-moderate risk of coronary artery disease (CAD). Methods This was a prospective, open-label, randomized study in which 127 patients were enrolled and randomized (ratio 1:1) into rosuvastatin and control groups. Results Rosuvastatin increased retinal arteriolar calibers by 3.560 µm at 12 months, decreased retinal venular calibers by 3.110 µm at 6 months and by 5.860 µm at 12 months, and increased the artery–vein ratio (AVR) by 2.68% at 6 months and by 5.90% at 12 months. Meanwhile, in the control group, retinal arteriolar calibers decreased by 1.110 µm at 12 months, retinal venular calibers increased by 1.020 µm at 6 months and by 1.04 µm at 12 months, and AVR decreased by 1.12% at 6 months and by 1.73% at 12 months. All the above parameters were statistically significant between groups, but there was no significant change in retinal arteriolar calibers at 6 months. The increased AVR correlated significantly with decreased C-reactive protein (CRP) at 6 months and decreased low-density lipoprotein and CRP at 12 months. Discussion For patients with a low-to-moderate risk of CAD, we found a significant effect of rosuvastatin on retinal microvasculature, including AVR increase, venular constriction, and arteriolar dilation after 6–12 months of treatment. Clinical Trial registration Chinese Clinical Trial Registry identifier number ChiCTR-IOR-15006664.

Clinical Outcomes at 2 Years Between Beta-Blockade with ACE Inhibitors or ARBs in Patients with AMI Who Underwent Successful PCI with DES: A Retrospective Analysis of 23,978 Patients in the Korea AMI Registry Abstract Introduction Data concerning the clinical impact of combination therapy with β-blockers (BBs) + angiotensin-converting enzyme inhibitors (ACEIs) compared with BBs + angiotensin-receptor blockers (ARBs) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) are limited. Objective We compared the clinical outcomes at 2 years between these two combination therapies. Methods We enrolled 23,978 patients with AMI who underwent successful PCI with DES between January 2005 and June 2015 from the Korea AMI Registry (KAMIR) and divided them into the two groups: BB + ACEI (n = 17,310) and BB + ARB (n = 6668). The primary endpoint was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR. The secondary endpoints were the cumulative incidences of individual components of MACE and target vessel failure (TVF), a composite of death related to the target vessel, re-MI, or clinically driven TVR. Results The relative risk of MACE was higher in the BB + ARB group than in the BB + ACEI group after propensity score-matched (PSM) analysis (hazard ratio [HR] 1.204; 95% confidence interval [CI] 1.057–1.370; p = 0.005). The relative risks of all-cause death (HR 1.435 [95% CI 1.117–1.845]; p = 0.005), cardiac death (HR 1.733 [95% CI 1.253–2.396]; p = 0.001), TVR (HR 1.437 [95% CI 1.157–1.784]; p = 0.001), and TVF (HR 1.231 [95% CI 1.065–1.424]; p = 0.005) were also higher in the BB + ARB group after PSM. Conclusions The BB + ACEI group demonstrated reduced cumulative incidences of MACE, all-cause death, cardiac death, TVR, and TVF compared with the BB + ARB group in patients with AMI who underwent successful PCI with DES during a 2-year follow-up period.

Anticoagulation in Venous Thromboembolism Prophylaxis in Medically Ill Patients: Potential Impact of NOACs Abstract While substantial evidence supports the use of standard-duration injectable anticoagulants for venous thromboembolism (VTE) prophylaxis, consensus is mixed about which agents may be preferred in acutely ill patients with ongoing need of VTE prophylaxis past the first 10-day duration of hospital stay and post-discharge. Non-vitamin K antagonist oral anticoagulants (NOACs) provide Factor Xa inhibition to prevent the thrombin generation essential in thromboembolism development, but evidence for the efficacy and safety of most NOACs is conflicting regarding extended-duration prophylaxis. Enoxaparin, a preferred injectable anticoagulant in standard-duration VTE prophylaxis, has shown an increased risk of major bleeding events when used in extended-duration prophylaxis, which outweighs its benefit. Rivaroxaban has demonstrated efficacy in extended-duration prophylaxis, but both rivaroxaban and apixaban have shown increased risks of major bleeding. Betrixaban remains the only NOAC approved in the USA for extended-duration VTE prophylaxis, and it demonstrates efficacy, with fewer adverse effects than other NOACs. This review evaluates the appropriateness of different NOAC agents compared with current therapies for the extended-duration VTE prophylaxis setting in medically ill populations.