1.
Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgery.
Zhao, N, Xu, J, Singh, B, Yu, X, Wu, T, Huang, Y
The Cochrane database of systematic reviews. 2016;(8):CD010726
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Abstract
BACKGROUND Cardiac complications are not uncommon in patients undergoing non-cardiac surgery, especially in patients with coronary artery disease (CAD) or at high risk of CAD. Perioperative cardiac complications can lead to mortality and morbidity, as well as higher costs for patient care. Nitrates, which are among the most commonly used cardiovascular drugs, perform the function of decreasing cardiac preload while improving cardiac blood perfusion. Sometimes, nitrates are administered to patients undergoing non-cardiac surgery to reduce the incidence of cardiac complications, especially for patients with CAD. However, their effects on patients' relevant outcomes remain controversial. OBJECTIVES • To assess effects of nitrates as compared with other interventions or placebo in reducing cardiac risk (such as death caused by cardiac factors, angina pectoris, acute myocardial infarction, acute heart failure and cardiac arrhythmia) in patients undergoing non-cardiac surgery.• To identify the influence of different routes and dosages of nitrates on patient outcomes. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Chinese BioMedical Database until June 2014. We also searched relevant conference abstracts of important anaesthesiology or cardiology scientific meetings, the database of ongoing trials and Google Scholar.We reran the search in January 2016. We added three potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into our formal review findings for the review update. SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing nitrates versus no treatment, placebo or other pharmacological interventions in participants (15 years of age and older) undergoing non-cardiac surgery under any type of anaesthesia. DATA COLLECTION AND ANALYSIS We used standard methodological procedures as expected by Cochrane. Two review authors selected trials, extracted data from included studies and assessed risk of bias. We resolved differences by discussion and, when necessary, sought help and suggestions from a third review author. We used a random-effects model for data analysis. MAIN RESULTS We included 27 randomized controlled trials (RCTs) (8244 participants analysed). Investigators reported 12 different comparisons of three different nitrates (nitroglycerin, isosorbide dinitrate and nicorandil) versus no treatment, placebo or other pharmacological interventions. All participants were older than 15 years of age. More than half of the trials used general anaesthesia. Surgical procedures in most trials were at low to moderate risk for perioperative cardiac complications. Only two comparisons including three studies reported the primary outcome - all-cause mortality up to 30 days post operation. Researchers reported other morbidity outcomes and adverse events in a variable and heterogeneous way, resulting in limited available data for inclusion in the meta-analysis. We determined that the overall methodological quality of included studies was fair to low, in accordance with risk of bias in most domains.In summary, we found no difference in the primary outcome - all-cause mortality up to 30 days post operation - when nitroglycerin was compared with no treatment (one study, 60 participants, 0/30 vs 1/30; (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to 7.87, very low-quality evidence based on GRADE criteria) or with placebo (two studies, 89 participants, 1/45 vs 0/44; RR 2.81, 95% CI 0.12 to 63.83, very low-quality evidence). Regarding our secondary outcomes, we noted no statistically significant differences in angina pectoris, acute myocardial infarction, acute heart failure, cardiac arrhythmia or cardiac arrest in any comparisons. In comparisons versus nitroglycerin, although more events of cardiac ischaemia were observed in participants receiving no treatment or placebo, we found no statistically significant differences in any comparisons, except the comparison of nicorandil versus placebo. One study revealed a potential dose-dependent protective effect of nicorandil for cardiac ischaemia.Adverse events were reported in a heterogeneous way among the comparisons. In general, more participants treated with nitrates had hypotension, tachycardia and headache, but investigators reported no statistically significant differences between groups in any comparisons. AUTHORS' CONCLUSIONS This systematic review suggests that nitroglycerin or isosorbide dinitrate is not associated with improvement in mortality and cardiac complications among patients undergoing non-cardiac surgery. Limited evidence suggests that nicorandil may reduce the risk of cardiac ischaemia in participants undergoing non-cardiac surgery. Additional studies are needed to consolidate the evidence.However, the data included in many of the analyses in this review are sparse - that is, adequate data are few - resulting in very low power to detect differences between nitrates and comparators. Thus, a more objective conclusion would state that available evidence is insufficient to show whether nitrates are associated with improvement in mortality and cardiac complications among patients undergoing non-cardiac surgery.Over the past decade, no high-quality studies have focused on association of cardiac mortality and morbidity with use of nitrates during non-cardiac surgery. This review underlines the need for well-designed trials in this field.
2.
Is tongxinluo more effective than isosorbide dinitrate in treating angina pectoris? A systematic review and meta-analysis of randomized controlled trials.
Jia, Y, Bao, F, Huang, F, Leung, SW
Journal of alternative and complementary medicine (New York, N.Y.). 2011;(12):1109-17
Abstract
BACKGROUND Tongxinluo (TXL), consisting of 12 Chinese Materia Medica items catalogued in the Chinese Pharmacopoeia, is commercially available in China, South Korea, and Russia. Hundreds of randomized clinical trials (RCTs) on TXL in treating cardiovascular diseases were conducted and published in China. This study provides a comprehensive Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review with sensitivity and subgroup analyses to evaluate the evidence about whether TXL is more effective than isosorbide dinitrate (ISDN) in treating ischemic heart disease, particularly angina pectoris. METHODS RCTs published between 1996 and 2010 on TXL versus ISDN in treating angina pectoris for at least 4 weeks were retrieved from eight bibliographical databases (e.g., MEDLINE,(®) PubMed, Chinese National Knowledge Infrastructure, Cochrane Library, and WanFang Data). The quality of RCTs was assessed with the Jadad scale. Meta-analysis was performed to estimate the overall effects based on symptomatic and electrocardiographic (ECG) improvements. Subgroup analysis, sensitivity analysis, and meta-regression were conducted on the study characteristics of RCTs. RESULTS Twenty (20) RCTs with a total of 1936 participants were included after eligibility assessment. The Jadad score of all included studies was 2. The means of summary odds ratios (ORs) for comparing TXL and nitrates were 3.30 (95% confidence interval [CI] 2.37-4.58) by symptoms (n=20) and 2.38 (95% CI 1.846-3.09) by ECG (n=18). There was a significant correlation of ORs between symptoms and ECG (ρ=0.77 and p=0.00026). Subgroup analysis, sensitivity analysis, and meta-regression found no significant difference in overall effects among all study characteristics except the years of publication (p=0.0409). CONCLUSIONS The meta-analysis of 20 eligible RCTs demonstrates moderate evidence that TXL is more effective than ISDN for treating angina pectoris. This result warrants further RCTs of multicenters/countries, larger sample sizes, and higher quality.
3.
From hypertension to heart failure: role of nitric oxide-mediated endothelial dysfunction and emerging insights from myocardial contrast echocardiography.
Lapu-Bula, R, Ofili, E
The American journal of cardiology. 2007;(6B):7D-14D
Abstract
There is growing evidence that nitric oxide (NO)-mediated endothelial dysfunction occurs in hypertension and may represent the earliest stage of target organ damage, which ultimately leads to hypertensive heart disease and heart failure (HF). An understanding of how impaired myocardial microvascular function and flow reserve relate to early remodeling during the transition to HF in patients with hypertension may lead to new therapeutic insights. The hypertrophied heart, which is a feature of the adverse structural remodeling in hypertensive heart disease, may be accompanied by impaired coronary flow reserve (CFR). Reduced CFR could potentially cause subendocardial ischemia during conditions of high metabolic demand, such as uncontrolled hypertension and tachycardia. Such vulnerability of the subendocardium to abnormal perfusion or ischemia may accelerate the progression from compensated hypertrophy to HF. In this review, we discuss preliminary evidence that altered NO balance may contribute to cardiac hypertrophy-mediated myocardial ischemia. We also describe early results with myocardial contrast echocardiography in the postulated transition from compensated hypertrophy to cardiac failure. These data support further evaluation of NO mediators as potential targets for novel therapies in hypertensive heart disease.
4.
Responses to cardiovascular drugs during alcohol withdrawal.
Kähkönen, S
Alcohol and alcoholism (Oxford, Oxfordshire). 2006;(1):11-3
Abstract
AIM: To present findings on the kinetics and dynamics of cardiovascular drugs during alcohol withdrawal (AW), compared with that observed in remission. METHOD Studies were reviewed and summarized. RESULTS A single-dose study in alcoholic patients with propranolol, a beta-adrenergic antagonist, showed that the negative inotropic effect was decreased and the bradycardiac effect increased during AW as compared with during early remission. The hypotensive effect of isosorbid dinitrate, commonly used as a vasodilatator, was weaker at the onset of AW, being associated with the decreased bioavailability of the drug. Verapamil, which is a L-type Ca2+ channel antagonist, produced a bradycardiac effect at the onset of AW, but no effect was observed in early remission. The effect was probably due to changes in L-type Ca2+ channels because no differences in verapamil concentrations between AW and early remission were observed. CONCLUSION Taken together, AW modifies the dynamics and kinetics of cardiac drugs, which may have an impact on the treatment of alcoholic patients with cardiac diseases.