A practical approach to switch from a multiple pill therapeutic strategy to a polypill-based strategy for cardiovascular prevention in patients with hypertension.

: Pharmacological treatment recommended by guidelines for very high-risk patients with established cardiovascular disease (CVD) includes lipid-lowering drugs, antihypertensive agents and antiplatelet therapy. Depending on the associated comorbidities, this baseline regimen has to be complemented with other drugs. Therefore, the number of pills to be taken is usually high and adherence to these multiple pill therapeutic regimens and long-term persistence on treatment is low, being the main factor for insufficient control of cardiovascular risk factors. The CNIC (Centro Nacional de Investigaciones Cardiovasculares, Ministerio de Ciencia e Innovación, España) polypill is the only polypill containing low-dose aspirin approved by the EMA and marketed in Europe, and has demonstrated to improve adherence. For this reason, guidelines recommend its use for secondary prevention of CVD, and also for primary prevention of cardiovascular events in patients with multiple cardiovascular risk factors and advanced atherosclerotic process at high risk of thrombosis and low risk of bleeding. This article pretends to simplify the steps that clinicians may follow to switch from any baseline regimen to the polypill with the use of several algorithms and tables showing the equivalent effective daily doses of different angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins to facilitate switching, as well as the steps to be followed depending of the initial levels of BP and LDL-cholesterol values to achieve BP and lipid control with the association to the polypill of other BP-lowering or lipid-lowering drugs whenever needed.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

AIMS: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. METHODS AND RESULTS: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50-60%) on admission vs. 60% (IQR: 55-60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. CONCLUSIONS: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data.

Perioperative SBP changes during orthopedic surgery in the elderly: clinical implications.

OBJECTIVES: We aimed to determine SBP changes during the perioperative period of a scheduled knee surgery under regional anesthesia and the extent of perioperative (in-hospital) white-coat effect. METHODS: All patients (aged ≥60 years) underwent clinic SBP measurements during both cardiological and anesthesiological visits, while home SBP the week before admission was obtained. Clinic SBP was registered just before surgery, during surgery and reanimation. Ambulatory monitoring was also performed (12 h before surgery to 6-8 h after surgery). One month after discharge, clinic SBP was measured at hypertension unit. RESULTS: Eligible participants (N = 50, mean age 74 ±â€Š7 years, 34% men, 26% with history of cardiovascular disease) had higher SBP during the anesthesiologic than the cardiological evaluation (157 ±â€Š23 vs. 144 ±â€Š18 mmHg, P < 0.001), and the former levels were almost identical to those clinically measured just before surgery. A significant white-coat effect between ambulatory and clinic measurements just before surgery (16.4 ±â€Š21 mmHg, P < 0.001) and between entire ambulatory recording and clinic BP measurements the day before surgery (12.4 ±â€Š16 and 24.8 ±â€Š21 mmHg for cardiologic and anesthesiologic visit, respectively, P < 0.001 for both) was noticed, whereas intraoperatively the white-coat effect faded away. There was a greater SBP decline during surgery in patients aged more than 75 years compared with younger, whereas selective treatment discontinuation (except beta blockers and calcium channel blockers) did not modulate SBP trajectories. CONCLUSION: The significant white-coat effect observed in scheduled noncardiac surgery is clinically important and the home BP measurement performed before surgery or ABPM, highly reflects the hypertensive burden of the patient. Blood pressure decrease during surgery is quite pronounced especially in patients aged more than 75 years. Aggressive BP lowering should be avoided.

Trimetazidine in the Prevention of Tissue Ischemic Conditions.

Trimetazidine (TMZ) is a metabolic agent with significant anti-ischemic properties. By inhibiting the terminal enzyme in the ß-oxidation pathway, it shifts the energy substrate metabolism, enhancing glucose metabolism. Thus, it maintains the required energy production with less oxygen consumption, an effect necessary in cases of myocardi. Trimetazidine was recently reaccredited as add-on therapy for symptomatic treatment in patients with stable angina, not adequately controlled or intolerant to first-line therapy. Trimetazidine was included in the European Society of Cardioloy 2013 guidelines for the management of stable coronary artery disease. Although TMZ has been used in cardiology for >40 years, only a few studies have assessed its effects in patients with acute ischemic conditions. This review summarizes the current literature regarding the addition of TMZ in patients with acute ischemic conditions (acute myocardial infarction, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting). There is growing evidence from recent studies that the addition of TMZ in patients with such conditions is beneficial in terms of myocardial damage and major cardiac events as well as decreasing reperfusion injury and contrast-induced nephropathy.

Adverse Effects of Mineralocorticoid Receptor Antagonist Administration.

BACKGROUND: Mineralocorticoid receptor antagonists consist of a class of drugs with pleiotropic beneficial effects in several cardiovascular diseases. However, physicians frequently overlook their use due to the adverse effects of such agents. OBJECTIVES: To determine the adverse effects of mineralocorticoid receptor antagonists and to suggest clinically meaningful options. We present data on the two most administered agents of this class: spironolactone and eplerenone. METHOD: We conducted an in-depth review of the existing international literature to draft a mini review about the mineralocorticoid receptor antagonists-related side effects. RESULT: Mineralocorticoid receptor antagonists are associated with increased risk of hyperkalemia and acute deterioration of renal function. Of note, these adverse effects are dose-dependent, more common during the initial period of treatment, and are usually reversed after the withdrawal of therapy. Sex-related adverse events are noted mainly in spironolactone while switching to eplerenone could attenuate those. CONCLUSION: Mineralocorticoid receptor antagonists therapy is significantly limited due to their side effects. The development of novel non-steroidal mineralocorticoid receptor antagonists could substantially widen the use of such agents.

The polypill in cardiovascular prevention: evidence, limitations and perspective - position paper of the European Society of Hypertension.

: Antihypertensive, lipid lowering, antidiabetic and antiplatelet treatments all substantially reduce the risk of cardiovascular morbid and fatal events. In real life, however, effective implementation of these treatments is rare, and thus their contribution to cardiovascular prevention is much less than it could be, based on research data. This article reviews the pros and cons of cardiovascular prevention by the polypill approach. It is argued that the high prevalence of individuals with a multifactorial risk profile provides a strong rationale for a therapeutic strategy based on the combination in a single tablet of drugs against different risk factors. It is further argued that other important favourable arguments exist. First, in real-life adherence to all above treatments is very low, leading to a major increase in the incidence and risk of cardiovascular outcomes. Second, although a large number of factors are involved, adherence is adversely affected by the complexity of the prescribed treatment regimen and can be considerably improved by treatment simplification. Third, recent studies in patients with a history of manifest cardiovascular disease have documented that different cardiovascular drugs can be combined in a single tablet with no loss of their individual efficacy or unexpected inconveniences and this does favour adherence to treatment and multiple risk factor control, supporting use of the polypill in secondary cardiovascular prevention. It is finally also mentioned, however, that the polypill may have some drawbacks and that at present no evidence is available that this approach reduces cardiovascular outcome to a greater degree than standard treatment strategies. Trials are under way to provide an answer to this question and thus allow the therapeutic value of this approach to be known.

Essential hypertension in the pathogenesis of age-related macular degeneration: a review of the current evidence.

Age-related macular degeneration (AMD) is one of the main causes of vision loss, especially in the elderly. The involvement of essential hypertension in its pathogenesis has been well covered in the literature since it was first recognized. Hemodynamic abnormalities appear to contribute to AMD, with the renin-angiotensin system playing a significant role. Many studies have demonstrated that high blood pressure is associated with lower choroidal blood flow and disturbed vascular homeostasis in these patients. In addition, AMD is characterized by abnormal neovascularization, to which angiotensin II and growth factors make a large contribution. Most epidemiological studies have found essential hypertension to be a risk factor for AMD. However, although all agree that the strongest predisposing factors are age and smoking, overall there is some inconsistency regarding the exact role of hypertension in its pathogenesis. In particular, there are no data in the literature to support the view that antihypertensive medication and the successful management of hypertension have a positive effect on the clinical outcome of AMD. This reinforces the data indicating that the cause of AMD is multifactorial and suggests that, although essential hypertension probably plays a role, in itself it is unlikely to be a major contributor to the future occurrence of AMD.

Adenosine as an Adjunct Therapy in ST Elevation Myocardial Infarction Patients: Myth or Truth?

Early reperfusion represents the key strategy in ST elevation myocardial infarction. However, reperfusion may induce myocardial damage due to the reperfusion myocardial injury, compromising the full potential of reperfusion therapy and accounting for unfavourable results in high risk patients. Adenosine seems to attenuate ischemia reperfusion injury, and thus represents a promising therapeutic option for treating such patients. However, previous randomized clinical trials have collectively failed to demonstrate whether adenosine can effectively reduce measures of myocardial injury and improve clinical outcome, despite its good basic evidence. The failure of such trials to show a real beneficial action may be in part related to specific factors other than adenosine's clinical efficacy. The purpose of this review is to explain the rationale for the use of adenosine as an adjunctive pharmacological cardio-protective agent following reperfusion of the ischemic myocardium, to address the weakness of previous trials and to summarize the current state of knowledge regarding the effect of adenosine administration on reperfusion myocardial injury in patients with myocardial infarction. Although some preclinical and clinical studies point towards the beneficial role of adenosine in the prevention and treatment of no-reflow phenomenon in myocardial infarction, many unanswered questions still remain, including the optimal clinical indication, mode, dosage, duration and timing of application, and the exact mechanisms leading to potential benefits. Clarifying these issues will depend on further properly designed, adequately powered and well conducted clinical trials, which will probably provide us with the definite answers.

The value of left ventricular global longitudinal strain assessed by three-dimensional strain imaging in the early detection of anthracyclinemediated cardiotoxicity.

INTRODUCTION: Anthracyclines are important anticancer drugs, but their use is limited by acute and chronic cardiotoxicity. Current approaches to surveillance are often inadequate to detect myocardial disease. Strain imaging might detect earlier myocardial dysfunction. Speckle analysis of three-dimensional (3D) echocardiography improves information about left ventricular (LV) segmental and global deformation by avoiding the loss of speckles seen in monoplane bidimensional-strain analysis. We assessed whether early 3D-strain analysis could predict later anthracycline-induced cardiotoxicity. METHODS: Echocardiography, troponin T (TnT) and N-terminal pro-brain natriuretic peptide were used to evaluate 59 patients (age 51 ± 10 years) before, and at 12 and 36 weeks after anthracycline treatment. LV global longitudinal strain (3DGLS), global radial strain (3DGRS) and global circumferential strain (3DGCS) were determined using 3D-strain imaging before and after 12 weeks of chemotherapy. Percentage changes from baseline to 12 weeks after initiation of chemotherapy () were calculated for all parameters analysed. RESULTS: During the follow-up period, eight patients (13.5%) developed cardiotoxicity. At 12 weeks after the initiation of chemotherapy, isovolumic relaxation time, 3DGLS, 3DGCS and 3DGRS had deteriorated and troponin was elevated (all p<0.05), before any decrease in LV ejection fraction. Cumulative anthracycline dose at 12 weeks, LVEF, 3DGLS and TnT were predictors of the later development of cardiotoxicity on univariate logistic regression. By multiple logistic regression, 3DGLS emerged as the only independent predictor of later cardiotoxicity (Odds ratio 1.09, p=0.04). CONCLUSIONS: Anthracycline therapy induced early deterioration of 3DGLS, 3DGCS and 3DGRS. 3DGLS seems to be a good predictor of the future development of anthracycline-induced cardiotoxicity.

Phentermine and topiramate extended-release for the obesity: new kids on the block.

Obesity is a major public health concern associated with increased morbidity and mortality. Its prevalence is rising worldwide mainly due to modern lifestyle habits. Several mechanisms like inflammation, endothelial dysfunction, increased sympathetic tone, high leptin and insulin concentrations as well as enhanced thrombogenesis are implicated to the emergence and progress of cardiovascular disease. Although, changes in the lifestyle remain the cornerstone of antiobesity treatment, alone do not always provide the desired weight loss. Often, the addition of pharmacotherapy or bariatric surgery is considered the treating option for patients meeting eligibility criteria. Although, bariatric surgery is limited to patients with a high body mass index due to the risks of the procedures, the effects of anti-obesity medication on cardiovascular outcome are still unclear. Several anti-obesity drugs have been abandoned because of serious adverse events. Qsymia is a combination of phentermine and topiramate used for obesity treatment. Administration of this drug reduces body weight and has favorable effects in various metabolic and anthropometric parameters. However, there are concerns regarding cardiovascular safety of this drug. In this review, we are going to present the history of current antiobesity medication focusing on the combination of phentermine and topiramate and recent patents.

The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized study. METHODS: The Angiotensin II Receptor Antagonist Micardis in Isolated Systolic hypertension (ARAMIS) study compared the antihypertensive efficacy after 6 weeks of once-daily fixed doses of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo in patients (n = 1039, aged 35-84 years) with ISH (seated blood pressure 150-179/< 90 mmHg). The prospective substudy analysed UAE using spot morning samples. RESULTS: Urinary albumin (> 2.2-901.6 mg/l) was detected at baseline in 614 out of 918 patients who were included in the substudy analysis. In the telmisartan group (n = 354, all doses combined), a median reduction in UAE from a baseline of 14.1% [95% confidence interval (CI) 7.3, 21.8] was observed versus 1.1% (95% CI -13.5 to 16.0) and 2.7% (95% CI -0.9 to 19.9) in the hydrochlorothiazide (n = 140) and placebo (n = 120) groups, respectively. The difference between telmisartan and hydrochlorothiazide was significant (P = 0.017). Reductions in UAE with telmisartan were observed in patients with baseline normoalbuminuria, microalbuminuria or macroalbuminuria. Telmisartan and hydrochlorothiazide produced comparable reductions in systolic blood pressure in these patients. CONCLUSION: In patients with ISH unselected for baseline albuminuria, telmisartan 20-80 mg after 6 weeks' treatment afforded significantly greater lowering of UAE than hydrochlorothiazide 12.5 mg, irrespective of the baseline UAE, and despite comparable reductions in systolic blood pressure with both drugs.