Improving Outcomes in Cardiovascular Diseases: A Review on Vorapaxar.

Antiplatelet agents are the standard of practice in the management of atherosclerosis and acute coronary syndrome. In contrast to the available antiplatelet agents, vorapaxar represents a novel mechanism of action. It is an antagonist of the platelet protease-activated receptor-1 and inhibits thrombin-induced and thrombin receptor agonist peptide-induced platelet aggregation. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) trial led to the approval of vorapaxar by the Food and Drug Administration and European Medicines Agency for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral arterial disease. TRA 2°P-TIMI 50 trial showed that the use of vorapaxar (2.5 mg once/daily) in addition to standard dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor was effective in the secondary prevention of recurrent thrombotic events among patients with previous atherothrombosis, particularly in patients with prior MI; at the expense of an increase in major bleeding. Another recently published Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y12 Receptor Inhibitors Prasugrel and Ticagrelor (VORA-PRATIC) study showed that among post-MI patients treated with potent P2Y12 inhibitors (prasugrel or ticagrelor), vorapaxar reduced platelet-driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin. The current review summarizes an up-to-date literature on pharmacokinetics, pharmacodynamics, and clinical efficacy of vorapaxar and proposes future directions of research.

Pacing therapies for sleep apnea and cardiovascular outcomes: A systematic review.

PURPOSE: Phrenic and hypoglossal nerve pacing therapies have shown benefit in sleep apnea. We sought to analyze the role of pacing therapies in sleep apnea and their impact on heart failure. METHODS: A comprehensive literature search in PubMed and Google Scholar from inception to August 5, 2019, was performed. A meta-analysis was performed using fixed effects model to calculate mean difference (MD) with 95% confidence interval (CI). RESULTS: Six studies were eligible and included 626 patients, of whom 334 were in the control arm and 393 were in the experimental arm. Phrenic nerve pacing (MD - 23.20 events/h, 95% CI - 27.96 to - 18.44, p < 0.00001) and hypoglossal nerve pacing (MD - 20.24 events/h, 95% CI - 23.22 to - 17.27, p < 0.00001) were associated with improvements in apnea-hypopnea index (AHI). Phrenic nerve pacing was associated with a trend towards improvements in left ventricular ejection fraction (MD 3.95%, 95% CI - 0.04 to 7.94, p = 0.05). Hypoglossal and phrenic nerve pacing were associated with improvements in the quality of life as assessed by improvements in Epworth sleepiness scale (MD 3.71 points, 95% CI 2.89 to 4.54, p < 0.00001). CONCLUSIONS: Our analysis suggests that phrenic and hypoglossal nerve pacing improves AHI and quality of life with a trend towards improvement in left ventricular ejection fraction, especially in central sleep apnea. Complications were high but future refinement in technology will likely improve clinical outcomes and minimize complications.

Role of cardiac sympathetic denervation in ventricular tachycardia: A meta-analysis.

BACKGROUND: Cardiac sympathetic denervation (CSD) is being used in the management of refractory ventricular tachycardia (VT) and electrical storm. However, data on the role of CSD in the management of ventricular arrhythmia is limited. METHODS: We performed a meta-analysis of retrospective studies to calculate the pooled rate of freedom from VT and the standard mean difference of ICD shocks before and after CSD. RESULTS: 14 nonrandomized studies with a total of 311 patients with refractory VT or electrical storm were included. At a mean follow up of 15 ± 10.7 months, the pooled rate of freedom from VT (VT nonrecurrence rate) after CSD in all causes of arrhythmia was 60% (range 48.8% to 70%, I2   = 43%). When analysis was restricted to only arrhythmias caused by conditions other than catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome (LQTS), the pooled VT non-recurrence rate was 50% (range 41% to 58%, I2   = 5%). After CSD, mean total number of ICD shocks per person diminished by 3.01 (95% CI 1.09-4.94, P = .002, I2  = 96%) in overall analysis and by 0.97(95% CI 0.41-1.5, P = .001, I2  = 45%) when CPVT and LQTS were excluded. CONCLUSION: In patients with refractory VT or electrical storm, CSD is associated with pooled VT nonrecurrence rate of 60% at a mean follow-up of 15 ± 10.7 months. CSD was also associated with significantly lower mean number ICD shocks per person. Further studies are needed to validate this finding in a prospective setting.

Baseline thrombocytopenia in women with coronary heart disease increases incident acute coronary syndrome: insights from national inpatient database.

There are paucity of data on gender-based differences in the effect of thrombocytopenia and coronary heart disease (CHD) towards development of acute coronary syndrome (ACS). We used National Inpatient Sample (NIS) database of the United States to assess the gender-based differences in the association of thrombocytopenia with CHD and the impact of thrombocytopenia on mortality, length of stay and hospitalization costs on ACS subgroup of CHD. Our analysis found that thrombocytopenia was associated with increased odds of CHD on univariate (odds ratio [OR] 1.31 (95% CI 1.30-1.32) p < 0.001) and multivariate (OR 1.36 (95% CI 1.34-1.38) p < 0.001) analyses. Thrombocytopenic CHD patients had increased odds of developing ACS only in women (OR 1.15, 95% CI 1.12-1.17, p < 0.001). Thrombocytopenia was found to be associated with poor short-term outcome in ACS subgroup of CHD with higher in-hospital mortality (OR 1.64, CI 1.58 to 1.71, p < 0.001), length of stay (3.4 days, CI 3.30-3.52, p < 0.001), and cost of hospitalization ($55,652, CI 53,717-57,587, p < 0.001). Thrombocytopenic women with ACS have greater odds of mortality compared to men. Our study suggests that thrombocytopenia among women with CHD is associated with increased odds of developing ACS. Women with ACS have greater mortality compared to men. Thrombocytopenic ACS patients have worse in-hospital outcome compared to patients with normal platelet count. We demonstrated association only and is not possible to establish causality with our study.

Ischemic and bleeding outcomes of triple therapy in patients on chronic anticoagulation undergoing percutaneous coronary intervention: A meta-analysis of randomized trials.

BACKGROUND: Triple therapy (TT) that includes oral anticoagulation and dual antiplatelet therapy is recommended in patients who are on chronic anticoagulation and undergo percutaneous coronary intervention (PCI). The randomized clinical trials (RCTs) comparing the effectiveness and safety of TT compared to double therapy (DT), which consists of an oral anticoagulation and one of the P2Y12 inhibitors, have shown increased risk of bleeding; however, none of the individual studies were powered to show a difference in ischemic outcomes. To compare the clinical outcomes of TT and DT, we performed this meta-analysis of RCTs. METHODS: Electronic search of PubMed, EMBASE and Cochrane CENTRAL databases was performed for RCTs comparing TT and DT in patients who were on oral anticoagulation (Vitamin K antagonist or non-vitamin K antagonist oral anticoagulant) who underwent PCI. All-cause and cardiovascular mortality, myocardial infarction (MI), stroke, stent thrombosis (ST) and TIMI major and minor bleeding were the major outcomes. RESULTS: An analysis of 5 trials including 10,592 total patients showed that TT, compared to DT, resulted in non-significant difference in risk of all-cause [odds ratio (OR); 1.14;95% confidence interval (CI):(0.80-1.63); P = 0.46) and cardiovascular mortality [1.43(0.58-3.36); P = 0.44], MI [0.88 (0.64-1.21); P = 0.42], stroke [1.10(0.75-1.62); P = 0.63] and ST [0.82(0.46-1.45); P = 0.49]. TT, compared to DT resulted in higher risk of TIMI major bleeding [1.61(1.09-2.37); P = 0.02], TIMI minor bleeding [1.85(1.23-2.79); P = 0.003] and TIMI major and minor bleeding [1.81 (1.38-2.38); P < 0.0001; I2 = 52%]. CONCLUSION: Compared to DT, the patients receiving TT are at a higher risk of major and minor bleeding with no survival benefit or impact on thrombotic outcomes.

An update on the epidemiology, length of stay, and cost of Kawasaki disease hospitalisation in the United States.

BACKGROUND: Kawasaki disease is an acute vasculitis of childhood and is the leading cause of acquired heart disease in the developed countries. METHODS: Data from hospital discharge records were obtained from the National Kids Inpatient Database for years 2009 and 2012. Hospitalisations by months, hospital regions, timing of admission, insurance types, and ethnicity were analysed. Length of stay and total charges were also analysed. RESULTS: There were 10,486 cases of Kawasaki disease from 12,678,005 children hospitalisation. Kawasaki disease was more common between 0 and 5 years old, in male, and in Asian. The January-March quarter had the highest rate compared to the lowest in the July-September quarter (OR=1.62, p < 0.001). Admissions on the weekend had longer length of stay [4.1 days (95 % CI: 3.97-4.31)] as compared to admissions on a weekday [3.72 days (95 % CI: 3.64-3.80), p < 0.001]. Blacks had the longest length of stay and whites had the shortest [4.33 days (95 % CI: 4.12-4.54 days) versus 3.60 days (95 % CI: 3.48-3.72 days), p < 0.001]. Coronary artery aneurysm was identified in 2.7 % of all patients with Kawasaki disease. Children with coronary artery aneurysm were hospitalised longer and had higher hospital charge. Age, admission during weekend, and the presence of coronary artery aneurysm had significant effect on the length of stay. CONCLUSIONS: This report provides the most updated epidemiological information on Kawasaki disease hospitalisation. Age, admissions during weekend, and the presence of coronary artery aneurysm are significant contributors to the length of stay.

Meta-Analysis Comparing Outcomes of Smokers Versus Nonsmokers With Acute Coronary Syndrome Underwent Percutaneous Coronary Intervention.

Several studies have found improved mortality in smokers after acute coronary syndrome (ACS) especially in the thrombolytic era. We aimed to assess the association of smoking status with mortality and cardiovascular outcomes in patients with ACS treated with percutaneous coronary intervention (PCI). We searched PubMed, EMBASE, CINAHL, and Cochrane CENTRAL for randomized controlled trials since inception through February 15, 2018 and used random effects model for analysis. The outcomes analyzed were all-cause mortality, major adverse cardiac events (MACE), myocardial infarction, and target vessel revascularization at 1 month and 1 year. We included 17 randomized and nonrandomized studies with a total of 55,491 patients with 21,989 smokers' and 33,502 nonsmokers. In ACS patients treated with PCI, smokers were found to have lower mortality than nonsmokers at 30-day ([2.3% vs 3.3%; Odds ratio; 0.54; 95% confidence interval: 0.39 to 0.76; p <0.001, I2 = 74%] and 1-year [2.3% vs 3.6%; Odds ratio 0.54 (0.3 to 0.7); p <0.001, I2 = 77%]. Meta-regression showed lower mortality in smokers was associated with younger age, man gender, and lower prevalence of diabetes mellitus. No significant differences were observed in myocardial infarction, MACE, and target-vessel revascularization between smokers and nonsmokers. In conclusion, smoking is associated with lower mortality but not MACE in ACS patients treated with PCI at 1-month and 1-year. This association with mortality was strongly associated with younger age, man gender, prevalence of diabetes mellitus, and extent of coronary artery disease.

Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure: A Systematic Review and Meta-analysis.

Importance: Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. Objectives: To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. Data Sources: PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. Study Selection: Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. Main Outcomes and Measures: The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. Results: In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, -0.43 to 3.24; P = .13). Conclusions and Relevance: Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.

Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Long-term aspirin use in cardiovascular disease prevention may result in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long-term aspirin users in the randomized controlled trials, there are safety concerns about the long-term use of PPI. STUDY QUESTION: What is the safety and efficacy of PPI in patients using aspirin in long term for prevention of cardiovascular diseases and stroke? METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, ProQuest, and relevant references from inception through February 2015, and used random-effects model for meta-analysis. RESULTS: A total of 10 publications from 9 studies (n = 6382) were included in the meta-analysis. Compared with control, PPI reduced the risks of peptic ulcers [risk ratio (RR): 0.19; 95% confidence interval: 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P < 0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22 (0.10-0.51); P = 0.0004], and erosive esophagitis [0.14 (0.07-0.28); P < 0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P = 0.01], heartburn [1.24 (1.18-1.31); P < 0.00001], and regurgitation [1.26 (1.13-1.40); P < 0.0001], but did not increase the risks of all-cause mortality [1.72 (0.61-4.87); P = 0.31], cardiovascular mortality [1.80 (0.59-5.44); P = 0.30], nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P = 0.22], ischemic stroke/transient ischemic attack [1.09 (0.34-3.53); P = 0.89] and other adverse events. CONCLUSIONS: The PPI seems to be effective in preventing peptic ulcers and erosive esophagitis and in resolution of dyspeptic symptoms without increasing adverse events, cardiac risks or mortality in long-term aspirin users.

Percutaneous coronary intervention vs coronary artery bypass grafting for left main coronary artery disease? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: It is not clear whether percutaneous coronary intervention (PCI) is as effective and safe as coronary artery bypass grafting (CABG) for left main coronary artery disease. We aimed to perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) that compared PCI and CABG in left main coronary disease. METHODS: We searched PubMed, EMBASE, Cochrane, Scopus and relevant references for RCTs (inception through, November 20, 2016 without language restrictions) and performed meta-analysis using random-effects model. All-cause mortality, myocardial infarction, revascularization rate, stroke, and major adverse cardiac and cerebrovascular events (MACCE) were the measured outcomes. RESULTS: Six RCTs with a total population of 4700 were analyzed. There was no difference in all-cause mortality at 30-day, one-year, and five-year (1.8% vs 1.1%; OR 0.60; 95% CI: 0.26-1.39; P=.23; I2 =9%) follow-up between PCI and CABG. CABG group had less myocardial infarction (MI) at five-year follow-up than PCI (5% vs 2.5%; OR 2.04; CI: 1.30-3.19; P=.002; I2 =1%). Revascularization rate favored CABG in one-year (8.6% vs 4.5%; OR 2; CI: 1.46-2.73; P<.0001; I2 =45%) and five-year (15.9% vs 9.9%; OR 1.73; CI: 1.36-2.20; P<.0001; I2 =0%) follow-up. Although stroke rate was lower in PCI group at 1 year, there was no difference in longer follow-up. MACCE at 5 years favored CABG (24% vs 18%; OR 1.45; CI: 1.19-1.76; P=.0001; I2 =0%). On subgroup analysis, MACCE were not different between two groups in low-to-intermediate SYNTAX group while it was higher for PCI group with high SYNTAX group. CONCLUSION: Percutaneous coronary intervention could be as safe and effective as CABG in a select group of left main coronary artery disease patients.

Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin.

BACKGROUND: Warfarin is a widely prescribed anticoagulant, and its effect depends on various patient factors including genotypes. Randomized controlled trials (RCTs) comparing genotype-guided dosing (GD) of warfarin with standard dosing have shown mixed efficacy and safety outcomes. We performed a meta-analysis of all published RCTs comparing GD vs standard dosing in adult patients with various indications of warfarin use. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and relevant references for English language RCTs (inception through March 2014). We performed the meta-analysis using a random effects model. RESULTS: Ten RCTs with a total of 2,505 patients were included in the meta-analysis. GD compared with standard dosing resulted in a similar % time in therapeutic range (TTR) at ≤ 1 month follow-up (39.7% vs 40.2%; mean difference [MD], -0.52 [95% CI, -3.15 to 2.10]; P = .70) and higher % TTR (59.4% vs 53%; MD, 6.35 [95% CI, 1.76-10.95]; P = .007) at > 1 month follow-up, a trend toward lower risk of major bleeding (risk ratio, 0.46 [95% CI, 0.19-0.1.11]; P = .08) at ≤ 1 month follow-up and lower risks of major bleeding (0.34 [95% CI, 0.16-0.74], P = .006) at > 1-month follow-up, and shorter time to maintenance dose (TMD) (24.6 days vs 34.1 days; MD, -9.54 days [95% CI, -18.10 to -0.98]; P = .03) at follow-up but had no effects on international normalized ratio [INR] > 4.0, nonmajor bleeding, thrombotic outcomes, or overall mortality. CONCLUSIONS: In the first month of genotype-guided warfarin therapy, compared with standard dosing, there were no improvements in % TTR, INR > 4.0, major or minor bleeding, thromboembolism, or all-cause mortality. There was a shorter TMD, and, after 1 month, improved % TTR and major bleeding incidence, making this a cost-effective strategy in patients requiring longer anticoagulation therapy.