Therapeutic Advances In Cardiovascular Disease[JOURNAL]
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200 papers
Metabolic syndrome: pathophysiology, management, and modulation by natural compounds.
Rochlani Y, Pothineni NV, Kovelamudi S … +1 more , Mehta JL
Ther Adv Cardiovasc Dis · 2017 Aug · PMID 28639538 · Full text
Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that include hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia, and is strongly associated with an increased risk fo...
Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that include hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia, and is strongly associated with an increased risk for developing diabetes and atherosclerotic and nonatherosclerotic cardiovascular disease (CVD). The pathogenesis of MetS involves both genetic and acquired factors that contribute to the final pathway of inflammation that leads to CVD. MetS has gained significant importance recently due to the exponential increase in obesity worldwide. Early diagnosis is important in order to employ lifestyle and risk factor modification. Here, we review the epidemiology and pathogenesis of MetS, the role of inflammation in MetS, and summarize existing natural therapies for MetS.
Challenges in management of left ventricular thrombus.
Habash F, Vallurupalli S
Ther Adv Cardiovasc Dis · 2017 Aug · PMID 28589748 · Full text
Left ventricular thrombus (LVT) complicates both ischemic and non-ischemic cardiomyopathies and is a potential cause of thromboembolic complications such as stroke. Management of LVT in the 21st century is primarily base...
Left ventricular thrombus (LVT) complicates both ischemic and non-ischemic cardiomyopathies and is a potential cause of thromboembolic complications such as stroke. Management of LVT in the 21st century is primarily based on studies before the widespread use of potent pharmacological and interventional therapies such as primary percutaneous coronary intervention, especially in the setting of acute myocardial infarction. Though advances in diagnostic technology have improved detection of LVT, clinicians face several uncertainties in the management of LVT in daily practice. The aim of this paper is to examine several controversies in the diagnosis and management of LVT. Prospective studies are needed to advance therapy of LVT.
Taurine supplementation has anti-atherogenic and anti-inflammatory effects before and after incremental exercise in heart failure.
Ahmadian M, Roshan VD, Aslani E … +1 more , Stannard SR
Ther Adv Cardiovasc Dis · 2017 Jul · PMID 28580833 · Full text
BACKGROUND: The purpose of this study was to examine the anti-atherogenic and anti-inflammatory effect of supplemental taurine prior to and following incremental exercise in patients with heart failure (HF). METHODS: Pat...
BACKGROUND: The purpose of this study was to examine the anti-atherogenic and anti-inflammatory effect of supplemental taurine prior to and following incremental exercise in patients with heart failure (HF). METHODS: Patients with HF and left ventricle ejection fraction less than 50%, and placed in functional class II or III according to the New York Heart Association classification, were randomly assigned to two groups: (1) taurine supplementation; or (2) placebo. The taurine group received oral taurine (500 mg) 3 times a day for 2 weeks, and performed exercise before and after the supplementation period. The placebo group followed the same protocol, but with a starch supplement (500 mg) rather than taurine. The incremental multilevel treadmill test was done using a modified Bruce protocol. RESULTS: Our results indicate that inflammatory indices [C-reactive protein (CRP), platelets] decreased in the taurine group in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation ( p < 0.05) whereas these indices increased in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation in the placebo group ( p < 0.05). Our results also show that atherogenic indices [Castelli's Risk Index-I (CRI-I), Castelli's Risk Index-II (CRI-II) and Atherogenic Coefficient (AC)] decreased in the taurine group in pre-exercise, post-supplementation and post-exercise, post-supplementation as compared with pre-exercise, pre-supplementation ( p < 0.05). No such changes were noted in the placebo group ( p > 0.05). CONCLUSIONS: our results suggest that 2 weeks of oral taurine supplementation increases the taurine levels and has anti-atherogenic and anti-inflammatory effects prior to and following incremental exercise in HF patients.
Cardiac rehabilitation in patients with ST-segment elevation myocardial infarction: can its failure be predicted?
Irzmański R, Kapusta J, Obrębska-Stefaniak A … +2 more , Urzędowicz B, Kowalski J
Ther Adv Cardiovasc Dis · 2017 Jul · PMID 28553755 · Full text
BACKGROUND: The prognosis in patients after acute coronary syndromes (ACS) is significantly burdened by coexisting anaemia, leukocytosis and low glomerular filtration rate (GFR). Hyperglycaemia in the early stages of ACS...
BACKGROUND: The prognosis in patients after acute coronary syndromes (ACS) is significantly burdened by coexisting anaemia, leukocytosis and low glomerular filtration rate (GFR). Hyperglycaemia in the early stages of ACS is a strong predictor of death and heart failure in non-diabetic subjects. This study aimed to evaluate the effect of hyperglycaemia, anaemia, leukocytosis, thrombocytopaenia and decreased GFR on the risk of the failure of cardiac rehabilitation (phase II at the hospital) in post-ST-segment elevation myocardial infarction (STEMI) patients. METHODS: The study included 136 post-STEMI patients, 96 men and 40 women, aged 60.1 ± 11.8 years, admitted for cardiac rehabilitation (phase II) to the Department of Internal Medicine and Cardiac Rehabilitation, WAM University Hospital in Lodz, Poland. On admission fasting blood cell count was performed and serum glucose and creatinine level was determined (GFR assessment). The following results were considered abnormal: glucose ⩾ 100 mg/dl, GFR < 60 ml/min/1, 73 m², red blood cells (RBCs) < 4 × 106/μl, white blood cells (WBCs) > 10 × 103/μl; platelets (PLTs) < 150 × 10³/ml. In all patients an exercise test was performed twice, before and after the completion of the second stage of rehabilitation, to assess its effects. RESULTS: Based on logistic regression analysis and the results of an individual odds ratio (OR) of the tested parameters, their prognostic impact was determined on the risk of failure of cardiac rehabilitation. This risk has been defined on the basis of the patient's inability to tolerate workload increment >5 Watt in spite of the applied program of cardiac rehabilitation. As a result of building a logistic regression model, the most statistically significant risk factors were selected, on the basis of which cardiac rehabilitation failure index was determined. leukocytosis and reduced GFR determined most significantly the risk of failure of cardiac rehabilitation (respectively OR = 6.42 and OR = 3.29, p = 0.007). These parameters were subsequently utilized to construct a rehabilitation failure index. CONCLUSIONS: Peripheral blood cell count and GFR are important in assessing the prognosis of cardiac rehabilitation effects. leukocytosis and decreased GFR determine to the highest degree the risk of cardiac rehabilitation failure. Cardiac rehabilitation failure index may be useful in classifying patients into an appropriate model of rehabilitation. These findings support our earlier reports.
The efficacy of evolocumab in the management of hyperlipidemia: a systematic review.
AlHajri L, AlHadhrami A, AlMheiri S … +2 more , AlMutawa Y, AlHashimi Z
Ther Adv Cardiovasc Dis · 2017 · PMID 28488460 · Full text
BACKGROUND: Hyperlipidemia or dyslipidemia has been a concern for a long time, with various guidelines emphasizing the importance of managing the lipid profile to prevent cardiac incidences. Although statins have been fo...
BACKGROUND: Hyperlipidemia or dyslipidemia has been a concern for a long time, with various guidelines emphasizing the importance of managing the lipid profile to prevent cardiac incidences. Although statins have been found to be highly effective, resistance and intolerability to side effects will continue to be a stumbling block for certain patients. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors tackle lipid profile via a novel mechanism and therefore provide an additional effective option for managing lipid profile. The overarching aim of this systematic review was to evaluate the efficacy of evolocumab among various populations with hypercholesterolemia. METHODS: A comprehensive search was conducted in ProQuest Health & Medical Complete, Google Scholar, ScienceDirect, and PubMed to identify potential records; then titles, abstracts, and full texts were screened using the inclusion criteria to filter out irrelevant studies. Data extraction and quality assessment were undertaken using standardized tools and the results were narratively synthesized and presented in tables. RESULTS: Eight studies were included in this systematic review after screening 1191 records. All studies demonstrated a statistically significant reduction in low-density lipoprotein cholesterol (LDL-C) values in the groups that received evolocumab compared with the comparator groups ( p < 0.05). The decline in LDL-C levels from baseline in the majority of studies ranged from 40% to 80%, whether used alone or in combination with other agents. Also, high-density lipoprotein cholesterol, lipoprotein (a) and apolipoprotein B were improved with the use of evolocumab. CONCLUSIONS: This study helped to collate evidence from studies that tested the effectiveness of evolocumab in the management of hyperlipidemia. Evolocumab seems to be highly effective in reducing LDL-C and other lipid parameters. Hence, it provides an excellent alternative for patients with refractory disease or patients who develop intolerable side effects, therefore helping to overcome the stumbling block to achieving optimal lipid management.
Tension pneumothorax presenting as ST segment elevation: Look, Listen, Act!
Chada AN, Pothineni NVKC, Kovelamudi S … +1 more , Raghavan DS
Ther Adv Cardiovasc Dis · 2017 Jul · PMID 28464707 · Full text
We present a unique case of a patient with a tension pneumothorax that presented with electrocardiogram (ECG) characteristics typical for ST segment elevation myocardial infarction. The clinical diagnosis was clinched by...
We present a unique case of a patient with a tension pneumothorax that presented with electrocardiogram (ECG) characteristics typical for ST segment elevation myocardial infarction. The clinical diagnosis was clinched by focused physical examination. Treatment of the pneumothorax lead to resolution of the electrocardiographic abnormalities. Our experience from this unique case is useful for cardiologists and critical care physicians who encounter these patients routinely.
DUSP-1 gene expression is not regulated by promoter methylation in diabetes-associated cardiac hypertrophy.
Singh GB, Khanna S, Raut SK … +3 more , Sharma S, Sharma R, Khullar M
Ther Adv Cardiovasc Dis · 2017 · PMID 28413926 · Full text
BACKGROUND: The exact mechanism causing decreased expression of the dual specific phosphatase-1 ( DUSP-1) gene in diabetes-associated cardiac hypertrophy is not known. DNA promoter methylation is often associated with de...
BACKGROUND: The exact mechanism causing decreased expression of the dual specific phosphatase-1 ( DUSP-1) gene in diabetes-associated cardiac hypertrophy is not known. DNA promoter methylation is often associated with decreased gene expression in many diseases including cardiovascular diseases. So, we investigated whether epigenetic silencing via promoter methylation is involved in the decreased expression of DUSP-1 in diabetes-associated cardiac hypertrophy. METHODS: Real-time polymerase chain reaction (PCR) and Western blotting confirmed the down regulation of the DUSP-1 gene at transcriptional and translational levels. Bisulfite-converted DNA samples from myocardium of rat model of diabetic cardiomyopathy (DCM), high glucose (HG)-treated neonatal rat cardiomyocytes (NRCMs) and cardiac tissues from archived human myocardial DCM autopsies along with their respective controls were analyzed for methylation in the promoter region of the DUSP-1 gene. RESULTS: We observed no methylation in the promoter regions of the DUSP-1 gene in DCM rat hearts, in HG-treated NRCMs (between -355 bp and -174 bp) and in cardiac tissues from archived human myocardial DCM autopsies (between -274 bp and -73 bp). CONCLUSION: Methylation-mediated silencing of the DUSP-1 promoter does not appear to be associated with reduced expression, indicating the involvement of other factors in specific suppression of DUSP-1 in diabetes-associated cardiac hypertrophy.
Nanomedicine applied to cardiovascular diseases: latest developments.
Martín Giménez VM, Kassuha DE, Manucha W
Ther Adv Cardiovasc Dis · 2017 Apr · PMID 28198204 · Full text
Cardiovascular diseases are a major cause of disability and they are currently responsible for a significant number of deaths in a large percentage of the world population. A large number of therapeutic options have been...
Cardiovascular diseases are a major cause of disability and they are currently responsible for a significant number of deaths in a large percentage of the world population. A large number of therapeutic options have been developed for the management of cardiovascular diseases. However, they are insufficient to stop or significantly reduce the progression of these diseases, and may produce unpleasant side effects. In this situation, the need arises to continue exploring new technologies and strategies in order to overcome the disadvantages and limitations of conventional therapeutic options. Thus, treatment of cardiovascular diseases has become one of the major focuses of scientific and technological development in recent times. More specifically, there have been important advances in the area of nanotechnology and the controlled release of drugs, destined to circumvent many limitations of conventional therapies for the treatment of diseases such as hyperlipidemia, hypertension, myocardial infarction, stroke and thrombosis.
Overview of the non-vitamin K oral anticoagulants for atrial fibrillation.
P Giugliano R
Ther Adv Cardiovasc Dis · 2017 Mar · PMID 28190378 · Full text
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Thrombolysis in peripheral artery disease.
Giannakakis S, Galyfos G, Sachmpazidis I … +7 more , Kapasas K, Kerasidis S, Stamatatos I, Geropapas G, Kastrisios G, Papacharalampous G, Maltezos C
Ther Adv Cardiovasc Dis · 2017 Apr · PMID 28164744 · Full text
Peripheral artery disease (PAD) has been associated with severe morbidity and mortality worldwide, affecting the quality of life for millions of patients. Acute thrombosis has been identified as a major complication of P...
Peripheral artery disease (PAD) has been associated with severe morbidity and mortality worldwide, affecting the quality of life for millions of patients. Acute thrombosis has been identified as a major complication of PAD, with proper management including both open as well as endovascular techniques. Thrombolysis has emerged as a reasonable option in the last decades to treat such patients although data produced by randomized trials have been limited. This review aims to present major aspects of thrombolysis in PAD regarding its indications and contraindications, technique tips as well as to review literature data in order to produce useful conclusions for everyday clinical practice.
Assessment of achieved systolic blood pressure in newly treated hypertensive patients aged 60-79 years before and after Eighth Joint National Committee recommendations.
Kelly MS, Saseen JJ, Marrs JC
Ther Adv Cardiovasc Dis · 2017 Feb · PMID 28033742 · Full text
OBJECTIVE: To determine whether patients who were newly prescribed antihypertensive therapy after the Eighth Joint National Committee (JNC 8) update were treated to a relaxed systolic blood pressure (SBP) goal compared w...
OBJECTIVE: To determine whether patients who were newly prescribed antihypertensive therapy after the Eighth Joint National Committee (JNC 8) update were treated to a relaxed systolic blood pressure (SBP) goal compared with patients treated before the update. METHODS: A retrospective cohort study approved by the Colorado Multiple Institutional Review Board. Patients aged 60-79 years, without diabetes or chronic kidney disease (CKD), newly treated for hypertension at a University of Colorado primary care clinics were included. The mean first-achieved and last-stable SBPs of patients newly prescribed antihypertensive medications from 1 January 2012 to 31 December 31 2013 (before cohort) were compared with patients newly prescribed antihypertensive therapy from 1 January 2014 to 1 October 2015 (after cohort). The mean number of antihypertensive medications at first-achieved SBP, the time to first-achieved SBP, and the class of initial antihypertensive medications were also evaluated. RESULTS: A total of 128 patients were included, 64 patients in each cohort. The coprimary outcome of first-achieved mean SBP did not differ between the groups (131.3 mmHg versus 130.2 mmHg; p = 0.65). Last-stable mean SBP values were also similar between the groups (130.2 mmHg versus 129.5 mmHg; p = 0.74). Angiotensin converting enzyme inhibitors (ACE-I) were the most frequently initiated antihypertensive agent in both cohorts (43.8% versus 48.4%; p = 0.72). CONCLUSIONS: Our findings suggest that the JNC 8 recommendations did not alter SBP goals among patients aged 60-79 years newly treated for hypertension at University of Colorado primary care clinics.
Effect of losartan combined with amlodipine or with a thiazide on uric acid levels in hypertensive patients.
Rubio-Guerra AF, Garro-Almendaro AK, Elizalde-Barrera CI … +2 more , Suarez-Cuenca JA, Duran-Salgado MB
Ther Adv Cardiovasc Dis · 2017 Feb · PMID 27932570 · Full text
UNLABELLED: Hyperuricemia leads to endothelial dysfunction and insulin resistance, and has been associated with diseases such as hypertension. Antihypertensive drugs modify serum uric acid levels, however, few data are a...
UNLABELLED: Hyperuricemia leads to endothelial dysfunction and insulin resistance, and has been associated with diseases such as hypertension. Antihypertensive drugs modify serum uric acid levels, however, few data are available about their combinations on uricemia. In this study we evaluate the effect of two combinations of losartan, with amlodipine or with hydrochlorothiazide, on serum uric acid levels in hypertensive patients. METHODS: A total of 60 hypertensive patients were randomized in two groups; group LA received losartan/amlodipine (100/5 mg) once a day, whereas LH group received losartan hydrochlorothiazide (100/12.5 mg) once a day for 3 months. In both groups serum uric acid levels were measured at the beginning and end of the study. Patients were evaluated monthly for blood pressure (BP) and adverse events. Statistical analysis was performed with a two-way analysis of variance (ANOVA) for repeated measures. RESULTS: All patients experienced a significant reduction of BP to the same extent (LA 155/94 to 123/79, LH 157/92 to 124/78 mmHg, p > 0.05). In the LA group, serum uric acid decreased from 6.5 ± 1.6 to 4.6 ± 1.3 mg/ml ( p = 0.0001), whereas in the LH group there was a nonsignificant increase from 5.82 ± 1.4 to 5.85 ± 1.5 mg/ml, ( p = 0.936). When both groups were compared, we found a significant reduction ( p < 0.00013) on serum uric acid levels in the LA group. CONCLUSIONS: Both combinations decrease BP values to the same extent, however, LA combination showed a reduction on serum uric acid levels, which may contribute to a reduction in the metabolic risk in hypertensive patients.
Control of blood pressure and cardiovascular risk in Moroccan patients with newly diagnosed hypertension: a 3-month observational study in primary care.
Alami M, El Hattaoui M, Seqat M … +3 more , Sadik J, Aouad A, Benghanem Gharbi M
Ther Adv Cardiovasc Dis · 2017 Feb · PMID 27884949 · Full text
BACKGROUND: Control of blood pressure and reduction of cardiovascular risk factors are mandatory in patients with hypertension. The aim of this study was to determine the proportion of patients with controlled hypertensi...
BACKGROUND: Control of blood pressure and reduction of cardiovascular risk factors are mandatory in patients with hypertension. The aim of this study was to determine the proportion of patients with controlled hypertension and to describe the cardiovascular risk profile in hypertensive patients followed by general practitioners (GPs) in Morocco. METHODS: This national, observational, multicentre, prospective, longitudinal study of patients with newly diagnosed hypertension was carried out between September 2011 and December 2011. The use of antihypertensive drugs was evaluated at inclusion and after 3 months of follow up. Uncontrolled hypertension was defined as systolic blood pressure (SBP) ⩾ 140 mmHg or diastolic blood pressure (DBP) ⩾ 90 mmHg at 3 months of follow up. The SCORE scale issued by the European Society of Cardiology (ESC) was used to assess overall cardiovascular risk and probability of experiencing a cardiovascular event within 10 years. RESULTS: A total of 909 hypertensive patients were recruited (62.4% female). Mean age was 56.8 ± 10.6 years. More than half of the patients (53.0%) were between 40-60 years and more than one-third (34.1%) were obese [body mass index (BMI) ⩾ 30 kg/m]. There were significantly more obese females than males ( p < 0.001). Over half of the patients (52.5%) had a high or extremely high cardiovascular risk. Abdominal obesity (measured as waist circumference) was the most common cardiovascular risk factor (61.7%) followed by age (40.5%), dyslipidaemia (36.3%) and diabetes (34.3%). Mean SBP decreased from 168.1 ± 14.8 to 138.3 ± 13.2 mmHg ( p < 0.001) and mean DBP decreased from 93.0 ± 10.5 to 81.0 ± 8.6 mmHg ( p < 0.001) after 3 months of treatment. Control of blood pressure was achieved in only 46.8% of patients. Poor compliance (17.1%) and a lack of treatment efficacy (16.9%) were the two main reasons for not achieving the blood pressure target. CONCLUSIONS: More than half (53.2%) of the hypertensive patients in our study did not achieve adequate blood pressure control during the 3-month follow-up period and had a high cardiovascular risk. More effective management of hypertension is required in primary care.
The protective role of vitamin D on the heart and the kidney.
Manucha W, Juncos LI
Ther Adv Cardiovasc Dis · 2017 Jan · PMID 27784812 · Full text
For a long time, vitamin D was regarded as an essential component for the maintenance of appropriate calcium metabolism. Indeed, the calcium-related functions were broadly studied and validated in numerous clinical and e...
For a long time, vitamin D was regarded as an essential component for the maintenance of appropriate calcium metabolism. Indeed, the calcium-related functions were broadly studied and validated in numerous clinical and epidemiologic studies. All of these vitamin D effects are mediated by a specific receptor. Remarkably, recent investigations show that the vitamin D receptor (VDR) also affects autoimmunity and by these means, the course of neoplasias and tissue inflammation. Moreover, the VDR regulates genes that affect cellular activity including cell differentiation and apoptosis and, by these means, angiogenesis. Actually, vitamin D deficiency has been associated with structural and functional cardiovascular changes that can be reversed by receptor stimulation. In this regard, some of the injurious effects of vitamin D deficiency such as myocardial hypertrophy and high blood pressure seem linked to increased renin-angiotensin activity. Interestingly, chronic renal disease, a condition often associated with greater cardiovascular risk, high blood pressure, myocardial hypertrophy and inappropriate stimulation of the renin angiotensin system, is also tied to inadequate vitamin D activity. In fact, studies in several animal models such as the rat ureteral obstruction model, the 5/6 nephrectomy model and others, clearly show that VDR stimulation prevents both structural and functional changes in the heart and the kidney. Clinical trials are needed to validate the vitamin D potential benefits in chronic kidney disease and its associated cardiovascular risk.
Novel oral anticoagulants for acute coronary syndrome.
Robinson A, McCarty D, Douglas J
Ther Adv Cardiovasc Dis · 2016 Oct · PMID 27765885 · Full text
Acute coronary syndrome (ACS) is a cardiovascular condition with a multifactorial pathophysiology that includes atherosclerotic plaques, platelet activation and thrombin production, among others. Thrombin production and...
Acute coronary syndrome (ACS) is a cardiovascular condition with a multifactorial pathophysiology that includes atherosclerotic plaques, platelet activation and thrombin production, among others. Thrombin production and the prothrombotic state of ACS patients have provided a role for anticoagulants to treat patients during the acute event and has led to subsequent research for the post-acute state. Warfarin has an indication for ACS, however, it is restricted to specific patients and many factors limit its use. Therefore, novel oral anticoagulants (NOACs) are being explored for ACS. Limitations for the use of NOACs in ACS are centered on the increased risk of bleeding that occurs when these agents are added to the current standard of care with dual antiplatelet therapy. Rivaroxaban is the only NOAC that has achieved approval in Europe for this indication with none of the NOAC currently approved in the US for use in ACS. Ongoing studies for rivaroxaban and apixaban may provide evidence to further clarify the place in therapy for NOAC agents in ACS management.
Emerging role of ivabradine for rate control in atrial fibrillation.
Turley SL, Francis KE, Lowe DK … +1 more , Cahoon WD
Ther Adv Cardiovasc Dis · 2016 Dec · PMID 27659287 · Full text
Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel block...
Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through I ('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment. Because I channels were thought to be expressed solely in sinoatrial (SA) nodal tissue, ivabradine was not investigated in heart failure patients with concomitant AF. Subsequent identification of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4), the primary gene responsible for I current expression throughout the myocardium, stimulated interest in the potential role of ivabradine for ventricular rate control in AF. Preclinical studies of ivabradine in animal models with induced AF demonstrated a reduction in HR, with no significant worsening of QT interval or mean arterial pressure. Preliminary human data suggest that ivabradine provides HR reduction without associated hemodynamic complications in patients with AF. Questions remain regarding efficacy, safety, optimal dosing, and length of therapy in these patients. Prospective, randomized studies are needed to determine if ivabradine has a role as a rate-control treatment in patients with AF.
Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall.
Araos P, Mondaca D, Jalil JE … +4 more , Yañez C, Novoa U, Mora I, Ocaranza MP
Ther Adv Cardiovasc Dis · 2016 Dec · PMID 27587602 · Full text
BACKGROUND: Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting o...
BACKGROUND: Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. METHODS: Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague-Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. RESULTS: All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p < 0.05) compared with control rats. All treatments reduced ROCK activation in the aortic wall to control levels (p < 0.05). Besides, significantly increased protein levels of transforming growth factor β1 (TGF-β), gene expression of TGF-β, connective tissue growth factor (CTGF), p22 phox and gp91 phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as well as increased media thickness and aortic media area/lumen area (AM/LA) in the untreated hypertensive rats were significantly reduced (p < 0.05) to control levels by all treatments. Similar effects were observed using both diuretics alone or in combination with FAS. CONCLUSIONS: In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients.
Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice.
Shah R, Patel MR
Ther Adv Cardiovasc Dis · 2017 Mar · PMID 27555569 · Full text
BACKGROUND: The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Emboli...
BACKGROUND: The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. METHODS: The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. RESULTS: Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. CONCLUSIONS: Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical management scenarios although the concurrent use of amiodarone requires more study.
Surrogate and clinical endpoints in interventional cardiology: are statistics the brakes?
Waliszewski M, Rittger H
Ther Adv Cardiovasc Dis · 2016 Oct · PMID 27378486 · Full text
BACKGROUND: Randomized controlled trials are the gold standard for demonstrating safety and efficacy of coronary devices with or without accompanying drug treatments in interventional cardiology. With the advent of last-...
BACKGROUND: Randomized controlled trials are the gold standard for demonstrating safety and efficacy of coronary devices with or without accompanying drug treatments in interventional cardiology. With the advent of last-generation drug-eluting stents having enhanced technical attributes and long-term clinical benefits, the proof of incremental angiographic or long-term clinical efficacy becomes more challenging. The purpose of this review is to provide an overview of the most common and alternative study endpoints in interventional cardiology and their potential reimbursement value. Moreover, we intend to describe the statistical limitations in order to demonstrate differences between potential treatment groups. Furthermore, careful endpoint recommendations for a given patient number are offered for future study designs. METHODS: The number of patients per treatment group was estimated for various study designs such as noninferiority test hypotheses with hard clinical endpoints and various surrogate endpoints. To test for differences in various surrogate endpoint scenarios, the corresponding patient group sizes were explored. To evaluate these endpoints in terms of their reimbursement impact, preferred endpoints for technical appraisals in interventional cardiology at the National Institute of Health and Care Excellence (NICE) were used. RESULTS: Even with the most stringent experimental control to reduce bias-introducing factors, studies with hard primary clinical endpoints such as the occurrence of major adverse cardiac events (MACE) or target-lesion revascularization (TLR) rates remain the gold standard, with numbers reaching into the 300-700 patient range per group. Study designs using loss in fractional-flow reserve (FFR) or stent-strut-coverage rates can be statistically formulated; however, the clinical ramifications for the patient remain to be discussed. Nonrandomized study designs with intrapatient angiographic controls in nontarget vessels may merit further thoughts and explorations. CONCLUSIONS: From a reimbursement impact, the primary endpoints MACE and TLR are the best choices for a moderately sized study population of 500 patients per group. Angiographic endpoints, in particular minimal lumen diameter (MLD), are not useful in this context. The emerging endpoints such as loss in FFR or stent coverage require smaller patient populations. However, their impact on reimbursement-related decisions is limited.
Apixaban to prevent stroke in patients with atrial fibrillation: a review.
Peterson BE, Al-Khatib SM, Granger CB
Ther Adv Cardiovasc Dis · 2017 Mar · PMID 27342651 · Full text
Atrial fibrillation is a common, costly and morbid cardiovascular arrhythmia. Stroke prevention remains the mainstay of treatment for atrial fibrillation, and the recent advent of novel oral anticoagulants with direct fa...
Atrial fibrillation is a common, costly and morbid cardiovascular arrhythmia. Stroke prevention remains the mainstay of treatment for atrial fibrillation, and the recent advent of novel oral anticoagulants with direct factor IIa or factor Xa inhibition has significantly revolutionized this aspect of treatment for atrial fibrillation patients. This review focuses on the tolerability and efficacy of apixaban and tackles the generalizability of the findings with apixaban to broader patient populations than those primarily enrolled in the clinical trials, drawing from the AVERROES and ARISTOTLE trials and their subsequent secondary analyses. Taken together, findings from these trials show that apixaban is superior to warfarin in preventing stroke with a lower risk of major bleeding in the general population of patients with atrial fibrillation as well as in several key high-risk patient subgroups.
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