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1.
The Effectiveness of Trimetazidine Treatment in Patients with Stable Angina Pectoris of Various Durations: Results from the CHOICE-2 Study.
Glezer, M, ,
Advances in therapy. 2018;(7):1103-1113
Abstract
INTRODUCTION Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease. METHODS CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina. RESULTS A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration. CONCLUSION TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life. FUNDING Servier. TRIAL REGISTRATION ISRCTN identifier ISRCTN65209863. Plain language summary available for this article.
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Route of Feeding as a Proxy for Dysphagia After Stroke and the Effect of Transdermal Glyceryl Trinitrate: Data from the Efficacy of Nitric Oxide in Stroke Randomised Controlled Trial.
Woodhouse, LJ, Scutt, P, Hamdy, S, Smithard, DG, Cohen, DL, Roffe, C, Bereczki, D, Berge, E, Bladin, CF, Caso, V, et al
Translational stroke research. 2018;(2):120-129
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Abstract
Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured at day 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ≤6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke. Clinical Trial Registration Clinical Trial Registration-URL: http://www.controlled-trials.com . Unique identifier: ISRCTN99414122.
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Acute Decompensated Heart Failure.
Hammond, DA, Smith, MN, Lee, KC, Honein, D, Quidley, AM
Journal of intensive care medicine. 2018;(8):456-466
Abstract
Heart failure (HF) is a societal burden due to its high prevalence, frequent admissions for acute decompensated heart failure (ADHF), and the economic impact of direct and indirect costs associated with HF and ADHF. Common etiologies of ADHF include medication and diet noncompliance, arrhythmias, deterioration in renal function, poorly controlled hypertension, myocardial infarction, and infections. Appropriate medical management of ADHF in patients is guided by the identification of signs and symptoms of fluid overload or low cardiac output and utilization of evidence-based practices. In patients with fluid overload, various strategies for diuresis or ultrafiltration may be considered. Depending on hemodynamics and patient characteristics, vasodilator, inotropic, or vasopressor therapies may be of benefit. Upon ADHF resolution, patients should be medically optimized, have lifestyle modifications discussed and implemented, and medication concierge service considered. After discharge, a multidisciplinary HF team should follow up with the patient to ensure a safe transition of care. This review article evaluates the management options and considerations when treating a patient with ADHF.
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[Effectiveness of trimetazidine prolong in stable coronary artery disease. Multicenter, prospective, observational study, ONECAPS study].
Tomcsányi, J, Szakács, L
Orvosi hetilap. 2018;(38):1549-1555
Abstract
INTRODUCTION The effectiveness of the manegement of stable coronary artery disease among outpatients is not well known. AIM: The aim of the study was to evaluate the effect of daily once trimetazidine prolong 80 mg on the angina number and severity (Canadian Cardiovascular Society class). METHOD This multicenter, prospective, observational, 3-month clinical study included 2160 patients, but only 1701 patients completed the study. The patients' mean age was 68 years (17% under 60 years). The start of angina was 7.8 ± 6.7 years. Hypertension (93.4%) and hypercholesterolemia (81%) were very common. RESULTS The patients were well treated with beta-blocking agents (88%), calcium antagonists (49%), angiotensin-converting enzym inhibitors (90%) and statin (77%) but only 5% received ivabradine and 50.5% was treated with trimetazidine MR. The patients attended 3 visits (inclusion, 1 month, 3 month). During the 3-month period, the weekly angina number of all patients treated with trimetazidine prolong 80 mg decreased from 2.55 to 0.41 (p<0.0001). A favorable effect was observed in CCS grading: CCS I. from 40.37% to 66.81%, CCS II. from 49.89% to 30.59%, CCS III. from 9.17% to 2% and CCS IV. from 0.56% to 0%. The mean office measured blood pressure decreased from 137/83 mmHg to 130/80 mmHg and the heart rate from 74 bpm to 71 bpm. CONCLUSIONS In the real-life, in the stable coronary artery disease the angina remains despite the medical treatment. Once a day administered trimetazidine prolong 80 mg significantly reduced the weekly number of angina and the severity, too. These beneficial effects mediated not only by antiischemic effect but also by increased medication adherence. Orv Hetil. 2018; 159(38): 1549-1555.
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Magnesium sulfate in combination with nimodipine for the treatment of subarachnoid hemorrhage: a randomized controlled clinical study.
Zhang, C, Zhao, S, Zang, Y, Zhao, W, Song, Q, Feng, S, Hu, L, Gu, F
Neurological research. 2018;(4):283-291
Abstract
Objective Cerebral vasospasm(CVS) after Subarachnoid hemorrhage (SAH) can cause delayed cerebral ischemia,secondary cerebral infarction, and rehemorrhage, which are the leading causes of mutilation and death. Nimodipine has been shown to prevent CVS. Magnesium ion (Mg2+) can competitively inhibit the influx of calcium (Ca2+) and prevent vasospasm. There is evidence that magnesium sulfate can prevent CVS and reduce infarct volume after SAH. In this study, we evaluated the efficacy and safety of intravenous magnesium sulfate combined with oral nimodipine on CVS, delayed cerebral ischemia, secondary cerebral infarction, and rehemorrhage after SAH. Methods This is a prospective randomized, double-blind trial of 120 patients with SAH who were recruited between January 2003 and January 2009. These patients were assigned to two groups and received the same basic treatment and symptomatic treatment. In group A, patients received 14 days of intravenous administration of 1400 mL 0.9% normal saline + 40 mL 25% magnesium sulfate, 1 mL/min, once per day, followed 7 days of intravenous administration of 500 mL 0.9% normal saline + 15 mL 25% magnesium sulfate, 1 mL/min, once per day and oral nimodipine, 20 mg once, four times a day, for 21 days. Patients in group B received identical treatment to that in group A, except that 25% magnesium sulfate was replaced by placebo. On day 22 of treatment, incidences of intracranial CVS, delayed cerebral ischemia, secondary cerebral infarction, rehemorrhage, neurologic deficits, and death were assessed and adverse events were monitored. Results CVS occurred in 4, 12 patients, lasting for 11.09 ± 5.38, 13.73 ± 6.24 hours, mean velocity (Vm) of 143.2 ± 12.7, 149.6 ± 18.9 cm/s in group A, B; Delayed cerebral ischemia occurred in 3, 10 patients, lasting for 13.16 ± 4.82, 15.57 ± 5.35 hours in group A, B; Secondary cerebral infarction occurred in 2 and 8 patients in groups A and B; Neurologic deficits occurred in3 and 11 patients in groups A and B, All P < 0.05; Rehemorrhage occurred in 4 and 5 patients; Death occurred in 5 and 8 patients in groups A and B, respectively, P >0.05. No obvious adverse events were found in both groups. Conclusion Intravenous magnesium sulfate in combination with oral nimodipine for the treatment of SAH can help reduce the incidences of CVS, delayed cerebral ischemia, secondary cerebral infarction, and neurologic deficits with good safety, but it does not reduce the incidences of rehemorrhage and death.
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Pharmacologic Treatment of Patients With Myocardial Ischemia With No Obstructive Coronary Artery Disease.
Turgeon, RD, Pearson, GJ, Graham, MM
The American journal of cardiology. 2018;(7):888-895
Abstract
Half of women and 1/3 of men with angina and ischemia on stress testing have ischemia with no obstructive coronary artery disease (INOCA). These patients have quality of life (QoL) impairment comparable with patients with obstructive coronary artery disease. Clinicians generally treat INOCA with traditional antianginal agents despite previous studies demonstrating variable response to these medications. We performed a systematic review to evaluate the efficacy and safety of available pharmacologic therapies for INOCA. We systematically searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and the World Health Organization International Clinical Trials Registry Platform in July 2017 for randomized controlled trials (RCTs) evaluating pharmacologic agents for INOCA. The primary outcome of interest was QoL. Secondary outcomes included subjective and objective efficacy measures and safety outcomes. We included 35 RCTs from 333 identified studies. Interventions that improved QoL with moderate-quality evidence included angiotensin-converting enzyme (ACE) inhibitor (±statin) and ranolazine. Low-to-very-low-quality evidence also suggests that ACE inhibitors, β blockers, calcium-channel blockers, nicorandil, ranolazine, and statins may decrease angina frequency and delay ischemia on stress testing. Other interventions, most notably nitrates, did not significantly improve any outcome. In conclusion, evidence for pharmacologic treatment of INOCA is generally poor, and higher-quality RCTs using a standardized definition of INOCA are needed. Moderate-quality evidence suggests that ACE inhibitors and ranolazine improve QoL. Other interventions had low-quality evidence or no evidence of efficacy.
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Effect of 6 wk of high-intensity one-legged cycling on functional sympatholysis and ATP signaling in patients with heart failure.
Munch, GW, Iepsen, UW, Ryrsø, CK, Rosenmeier, JB, Pedersen, BK, Mortensen, SP
American journal of physiology. Heart and circulatory physiology. 2018;(3):H616-H626
Abstract
Breathlessness during daily activities is the primary symptom in patients with heart failure (HF). Poor correlation between the hemodynamic parameters of left ventricular performance and perceived symptoms suggests that other factors, such as skeletal muscle function, play a role in determining exercise capacity. We investigated the effect of 6 wk of high-intensity, one-legged cycling (HIC; 8 × 4 at 90% one-legged cycling max) on 1) the ability to override sympathetic vasoconstriction (arterial infusion of tyramine) during one-legged knee-extensor exercise (KEE), 2) vascular function (arterial infusion of ACh, sodium nitroprusside, tyramine, and ATP), and 3) exercise capacity in HF patients with reduced ejection fraction ( n = 8) compared with healthy individuals ( n = 6). Arterial tyramine infusion lowered leg blood flow and leg vascular conductance at rest and during KEE before the training intervention in both groups ( P < 0.05) but not during KEE after the training intervention. There was no difference between groups. The peak vasodilatory response to ATP was blunted in HF patients ( P < 0.05), whereas there was no difference in ACh- and sodium nitroprusside-induced vasodilation between HF patients and healthy individuals. ACh-induced vasodilation increased in HF patients after the training intervention ( P < 0.05). HIC improved aerobic capacity in both groups ( P < 0.05), whereas only HF patients made improvements in the 6-min walking distance ( P < 0.05). These results suggest that exercise hyperemia and functional sympatholysis are not altered in HF patients and that functional sympatholysis is improved with HIC in both HF patients and healthy individuals. Moreover, these results suggest that the peak vasodilatory response to ATP is blunted in HF. NEW & NOTEWORTHY The ability to override sympathetic vasoconstrictor activity (by arterial tyramine infusion) during exercise is not different between heart failure patients and healthy individuals and is improved by high-intensity, one-legged cycling training. The peak vasodilatory response to ATP is reduced in heart failure patients.
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Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis.
Solernó, R, Pedroni, P, Mariani, J, Sarmiento, R
Expert review of cardiovascular therapy. 2018;(10):765-770
Abstract
BACKGROUND Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed. METHODS Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: 'fractional flow reserve' AND 'nitroprusside'. Data were summarized using weighted mean differences for paired data. RESULTS Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) -0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02-0.30, P < 0.0001). CONCLUSIONS NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.
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Effect of Nicorandil Administration on Preventing Contrast-Induced Nephropathy: A Meta-Analysis.
Zhan, B, Huang, X, Jiang, L, Bao, H, Cheng, X
Angiology. 2018;(7):568-573
Abstract
Several studies have investigated the effect of nicorandil on contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). However, the final results of these trials are not identical. This meta-analysis evaluated the role of nicorandil administration on CIN prevention. We searched databases to find randomized controlled trial (RCT) comparing nicorandil with hydration versus conventional hydration therapy on preventing CIN. Finally, 5 articles (805 patients) were included in our meta-analysis; the data showed that nicorandil was related to significant reduction in the risk of CIN (risk ratio = 0.37, 95% confidence interval [CI]: 0.22-0.61, P = .0001). We found not only the cystatin C level after operation was nonsignificant between 2 groups at the first 24 hours ( P = .65, 95% CI = -0.06 to 0.04) and 48 hours ( P = .19, 95% CI = -0.11 to 0.02) but also the serum creatinine level was nonsignificantly elevated, at 24 hours ( P = .46, 95% CI = -5.19 to 1.88) and 72 hours ( P = .49, 95% CI = -0.49 to 0.34). Our analysis suggested that the nicorandil treatment compared with conventional hydration can significantly reduce the risk of CIN.
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10.
Impact of Trimetazidine Treatment on 5-year Clinical Outcomes in Patients with Significant Coronary Artery Spasm: A Propensity Score Matching Study.
Kim, YH, Her, AY, Rha, SW, Choi, BG, Choi, SY, Byun, JK, Mashaly, A, Park, Y, Jang, WY, Kim, W, et al
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2018;(2):117-127
Abstract
OBJECTIVE We aimed to evaluate the additive benefit of trimetazidine with well-known antispasmodic agents such as calcium channel blockers and nitrate in patients with significant coronary artery spasm (CAS) as assessed by acetylcholine provocation test up to 5 years. METHODS A total 1727 patients with significant CAS were enrolled. They were divided into two groups: a trimetazidine group (trimetazidine, diltiazem, and nitrate, n = 695), and control group (diltiazem and nitrate, n = 473). After propensity score matching analysis, two matched groups (441 pairs, n = 882, C-statistic = 0.673) were generated. The individual and composite clinical end points [mortality, myocardial infarction (MI), revascularization, cerebrovascular accident (CVA), major adverse cardiac events (MACE), major adverse cardiac or cerebrovascular events (MACCE), and recurrent angina] were assessed up to 5 years for the two groups. RESULTS At 5 years, there were similar incidences of individual and composite hard endpoints including mortality, MI, revascularization, CVA, MACE, MACCE, and recurrent angina in the two groups. CONCLUSIONS Additional long-term (5-year) treatment with trimetazidine in combination with diltiazem and nitrate in patients with significant CAS was not associated with improved clinical outcomes compared with combination therapy with diltiazem and nitrate only (without trimetazidine).