Param Singh

Effect of Niacin Therapy on Cardiovascular Outcomes in Patients With Coronary Artery Disease

Background: Niacin or nicotinic acid (vitamin B3) raises the levels of high-density lipoprotein cholesterol (HDL) by about 30% to 35%. In patients with prior coronary disease, 7 trials have been published on clinical cardiovascular disease outcomes and the results, not surprisingly, are inconsistent. Hence, we performed this meta-analysis of randomized placebo-controlled trials (RCTs) to evaluate the effect of niacin on cardiovascular outcomes in patients with coronary artery disease. Methods: A systematic search using PubMed, EMBASE, and Cochrane library databases was performed. Seven studies with a total of 5137 patients met our inclusion criteria. Heterogeneity of the studies was analyzed by the Cochran Q statistics. The significance of common treatment effect was assessed by computing the combined relative risks using the Mantel-Haenszel fixed-effect model. A 2-sided alpha error of less than .05 was considered statistically significant (P < .05). Results: Compared to placebo group, niacin therapy significantly reduced coronary artery revascularization (RR [relative risk]: 0.307 with 95% CI: 0.150-0.628; P = .001), nonfatal myocardial infarction ([MI]; RR: 0.719; 95% CI: 0.603-0.856; P = .000), stroke, and TIA ([transient ischemic attack] RR: 0.759; 95%CI: 0.613-0.940; P = .012), as well as a possible but nonsignificant decrease in cardiac mortality (RR: 0.883: 95% CI: 0.773-1.008; p= 0.066). Conclusions: In a meta-analysis of seven trials of secondary prevention, niacin was associated with a significant reduction in cardiovascular events and possible small but non-significant decreases in coronary and cardiovascular mortality.

Outcomes of nonemergent percutaneous coronary intervention with and without on-site surgical backup: a meta-analysis.

Despite major advances in percutaneous coronary intervention (PCI) techniques, the current guidelines recommend against elective PCI at hospitals without on-site cardiac surgery backup. Nonetheless, an increasing number of hospitals without on-site cardiac surgery in the United States have developed programs for elective PCI. Studies evaluating outcome in this setting have yielded mixed results, leaving the question unanswered. Hence, a meta-analysis comparing outcomes of nonemergent PCI in hospitals with and without on-site surgical backup was performed. A systematic review of literature identified four studies involving 6817 patients. Three clinical end points were extracted from each study and included in-hospital death, myocardial infarction, and the need for emergency coronary artery bypass grafting. The studies were homogenous for each outcome studied. Therefore, the combined relative risks (RRs) across all the studies and the 95% confidence intervals (CIs) were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error less than 0.05 was considered to be statistically significant. Compared with facilities with on-site surgical backup, the risk of in-hospital death (RR, 2.7; CI, 0.6-12.9; P = 0.18), nonfatal myocardial infarction (RR, 1.3; CI, 0.7- 2.2; P = 0.29), and need of emergent coronary artery bypass grafting (RR, 0.46; CI, 0.06- 3.1; P = 0.43) was similar in those lacking on-site surgical backup. The present meta-analysis suggests that there is no difference in the outcome with regard to risk of nonfatal myocardial infarction, need for emergency coronary artery bypass grafting, and the risk of death in patients undergoing elective PCI in hospitals with and without on-site cardiac surgery backup.

Leptin and the clinical cardiovascular risk

Obesity is a universal health problem of increasing prevalence and represents a major public health concern. Obesity is associated with a high risk of developing cardiovascular and metabolic diseases such as hypertension, coronary atherosclerosis, myocardial hypertrophy, diabetes, dyslipidemia, and increased cardiovascular morbidity and mortality. There has been an ongoing search for mediators between obesity and cardiovascular disease. Leptin is a novel and very promising molecule of research that may link these pathologic conditions. Since its discovery in 1994, major advances have been made in the understanding of neuroendocrine mechanisms regulating appetite, metabolism, adiposity, sympathetic tone and blood pressure. In this review, we discuss the physiological and pathophysiological roles of leptin in the causation of various cardiovascular diseases.

Safety and efficacy of intracoronary adenosine administration in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials:

Background: Studies evaluating intracoronary administration of adenosine for prevention of microvascular dysfunction and ischemic-reperfusion injury in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) have yielded mixed results. Therefore, we performed a meta-analysis of these trials to evaluate the safety and efficacy of intracoronary adenosine administration in patients with AMI undergoing primary PCI. Methods: A total of seven prospective randomized controlled trials were analyzed. The endpoints extracted were post-procedure residual stent thrombosis (ST) segment elevation and ST segment resolutions (STRes), difference in peak creatine kinase (CK-MB) concentration, thrombolysis in myocardial infarction (TIMI) grade III flow (TIMI 3 flow), myocardial blush grade (MBG) 3, mean difference in post-PCI ejection fraction (EF), all-cause mortality, cardiovascular mortality, heart failure (HF) and major adverse cardiovascular event (MACE). Safety endpoints analyzed were bradycardia, second-degree atrioventricular block (AVB), ventricular tachycardia (VT), ventricular fibrillation (VF) and recurrence of chest pain (CP). The endpoints were analyzed by standard methods of meta-analysis. Results: Intracoronary adenosine therapy led to significantly more post-PCI STRes [relative risk (RR) 1.39, 95% confidence interval (CI) 1.01–1.90; p = 0.04] and reduction in residual ST segment elevation (RR 0.82, CI 0.69–0.99; p = 0.04) but did not improve TIMI 3 flow (RR 1.09, CI 0.94–1.27; p = 0.25), MBG3 (RR 1.04, CI 0.65–1.69; p = 0.88), peak CK-MB concentration (mean difference −39.43, CI −120.223 to 41.371; p = 0.339) and post-PCI EF (mean difference 1.238, CI −5.802 to 8.277; p = 0.730). There was a trend towards improvement and MACE (RR 0.64, CI 0.40–1.03; p = 0.06), incidence of HF (RR 0.47, CI 0.19–1.12; p = 0.08) and CV mortality (RR 0.15, CI 0.02–1.23; p = 0.08) that did not reach statistical significance but no difference in all-cause mortality (RR 0.77, CI 0.25–2.34; p = 0.64). Safety analysis showed no significant difference in CP events (RR 1.26, CI 0.55–2.86; p = 0.58), bradycardia (RR 2.19, CI 0.24–0.38; p = 0.49), VT (odds ratio 0.61, CI 0.08–4.90; p = 0.64) and VF (RR 0.49, CI 0.13–1.90; p = 0.30), but significantly more second-degree AVB (RR 7.88, CI 4.15–14.9; p < 0.01) in the adenosine group compared with the placebo group. Conclusion: Intracoronary adenosine administration was well tolerated and significantly improved electrocardiographic outcomes with a tendency towards improvement in MACE, HF and CV mortality that could not reach statistical significance.

Effects of Statins on Progression of Coronary Artery Disease as Measured by Intravascular Ultrasound

J Clin Hypertens (Greenwich). 2011;13:492–496.©2011 Wiley Periodicals, Inc.

Prevention of Recurrent Atrial Fibrillation With Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Systematic Review and Meta-Analysis of Randomized Trials:

Background: Controversy persists regarding the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in the prevention of recurrent atrial fibrillation (AF). We performed a meta-analysis of randomized controlled trials (RCTs), not designed a priori to test this hypothesis, to explore whether ACEs and ARBs reduce recurrent AF. Methods: We performed a systematic literature search for RCTs using ACEIs or ARBs and providing data on the outcome of recurrent AF. Statistical heterogeneity across the trials was tested using the Cochran Q statistic and I2 was computed to quantify heterogeneity. A 2-sided α error of less than .05 was considered statistically significant (P < .05). Results: The analysis was based on 8 RCTs including 2323 patients. The Mantel-Haenszel random-effect model was used to calculate relative risk (RR) for studies using ACEIs or ARBs, and for studies using ARBs. The fixed-effect model was used to calculate RR for studies using ACEIs. Meta-analysis of the studies revealed that ACEIs or ARBs significantly reduced the incidence of recurrent AF (RR, 0.611; 95% CI, 0.441-0.847; P = .003). The RR for recurrent AF was 0.643 (95% CI, 0.439-0.941; P = .023) for studies using ARBs and 0.54 (95% CI, 0.377-0.80; P = .002) for studies using ACEIs. Conclusion: In this meta-analysis of RCTs not designed a priori to test the hypothesis, ACEs and ARBs were associated with a significant reduction in recurrent AF. Large-scale randomized trials designed a priori to test the hypothesis are necessary to complete the totality of evidence.

Efficacy of Various Percutaneous Interventions for In-Stent Restenosis Comprehensive Network Meta-Analysis of Randomized Controlled Trials

Background—In-stent restenosis (ISR) remains a difficult problem in interventional cardiology. The relative efficacy and safety of available interventions is not clear. We aimed to perform a network meta-analysis using both direct evidence and indirect evidence to compare all available interventions. Methods and Results—We systematically searched electronic databases for randomized trials comparing ≥2 treatments for ISR. A network meta-analysis was performed using a Bayesian approach. Eleven treatments were compared in 31 studies with 8157 patient-years follow-up. Compared with balloon angioplasty, everolimus-eluting stent (hazard ratio [95% credibility interval], 0.13 [0.048–0.35]), paclitaxel-eluting balloon (0.32 [0.20–0.49]), paclitaxel-eluting cutting balloon (0.054 [0.0017–0.5]), paclitaxel-eluting stent (0.39 [0.24–0.62]), and sirolimus-eluting stent (0.32 [0.18–0.50]) are associated with lower target vessel revascularization. Balloon angioplasty is not different from cutting balloon (0.73 [0.31–1.5]), excimer laser (0.89 [0.29–2.7]), rotational atherectomy (0.96 [0.53–1.7]), and vascular brachytherapy (0.60 [0.35–1.0]). In drug-eluting stent ISR, balloon angioplasty was inferior to everolimus-eluting stent (0.19 [0.049–0.76]), paclitaxel-eluting balloon (0.43 [0.18–0.80]), paclitaxel-eluting stent (0.35 [0.13–0.76]), and sirolimus-eluting stent (0.36 [0.11–0.86]) for target vessel revascularization. There was no difference between treatments in probable or definitive stent thrombosis. The results of binary restenosis and target lesion revascularization were similar. Paclitaxel-eluting cutting balloon, everolimus-eluting stent, and paclitaxel-eluting balloon have the highest probability of being in the top 3 treatments based on low target lesion revascularization, but there was no statistical significant difference between them. Conclusions—Balloon angioplasty is inferior to all drug-eluting treatments for ISR, including drug-eluting stent ISR. Drug-eluting stent, particularly everolimus-eluting stent, or paclitaxel-eluting cutting balloon and paclitaxel-eluting balloon should be preferred for treating ISR.

Dronedarone for atrial fibrillation: a new therapeutic agent

Atrial fibrillation is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality. Amiodarone is currently one of the most widely used and most effective antiarrhythmic agents for atrial fibrillation. But during chronic usage amiodarone can cause some serious extra cardiac adverse effects, including effects on the thyroid. Dronedarone is a newer therapeutic agent with a structural resemblance to amiodarone, with two molecular changes, and with a better side effect profile. Dronedarone is a multichannel blocker and, like amiodarone, possesses both a rhythm and a rate control property in atrial fibrillation. The US Food and Drug Administration approved dronedarone for atrial fibrillation on July 2, 2009. In this review, we discuss the role of dronedarone in atrial fibrillation.

Safety and efficacy of triple antithrombotic therapy after percutaneous coronary intervention in patients needing long-term anticoagulation

Background: Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) is currently undefined in patients requiring long-term anticoagulation. Previous studies comparing triple therapy (TT) of warfarin, aspirin and clopidogrel with standard dual therapy (DT) of aspirin and clopidogrel have yielded conflicting results. Meta-analysis of these studies was performed to evaluate safety and efficacy of TT. Methods: A total of 1482 patients from 6 studies were analyzed using the Mantel–Haenszel random effect model to extract incidence of major bleeding. The secondary end point assessed by three of these studies was major adverse cardiac events (MACEs: cardiovascular death, myocardial infarction and thromboembolic complications). The incidence of MACEs was computed using the Mantel–Haenszel fixed effect model. Combined relative risks (RRs) across all of the studies and the 95% confidence intervals (CIs) were determined. A two-sided alpha error <0.05 was considered statistically significant. Results: Baseline characteristics were similar in both groups. Compared with patients receiving DT, the risk of major bleeding was significantly higher in the TT group (RR: 2.74, CI: 1.08–6.98; p = 0.034). However, risk of MACE was significantly lower in the TT group (RR: 0.72, CI: 0.56–0.98; p = 0.014). Conclusion: In patients requiring long-term anticoagulation after PCI, TT may be superior to DT in reducing the incidence of MACEs, however risk of major bleeding complications is increased significantly.

Safety and efficacy of transradial versus transfemoral percutaneous coronary intervention in acute myocardial infarction: a meta-analysis of randomized trials.

BackgroundThe transradial approach has gained increasing popularity for elective percutaneous coronary intervention. However, the safety and feasibility of transradial coronary intervention (TRI) in acute myocardial infarction (AMI) remains uncertain. Hence, a meta-analysis of randomized trials was performed to compare outcomes of TRI with transfemoral coronary intervention (TFI) in patients with AMI. MethodsA systematic review of the literature revealed seven randomized trials involving 1306 patients. Endpoints extracted were access site complications, major adverse cardiovascular events, major bleeding, and procedural success. Combined relative risks (RRs) across all studies and 95% confidence intervals (CIs) were computed. A two-sided &agr; error of less than 0.05 was considered to be statistically significant. ResultsBaseline characteristics were similar in both groups. Compared with patients undergoing TFI, risk of major adverse cardiovascular events (RR: 0.83, CI: 0.51–1.35; P=0.45) and major bleeding (RR: 0.51, CI: 0.20–1.26; P=0.14) was similar in patients undergoing TRI. The procedural success was similar with both approaches (RR: 0.99, CI: 0.96–1.02; P=0.59). However, incidence of access site complications was significantly lower in the TRI group (RR: 0.31, CI: 0.17–0.58; P<0.001). ConclusionThe meta-analysis suggests that TRI may be superior to TFI in reducing access site complications in patients with AMI. However, there is no difference in procedural success and major bleeding between the two groups.