STRUGGLE FOR. Italian-Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023 for better control of classical modifiable risk factors in clinical practice.

The progress in pharmacotherapy that has been made in recent years, including the introduction of very effective and safe lipid-lowering and antihypertensive drugs, has not yet translated into the expected universal control of blood pressure, lipid disorders and diabetes. In the STRUGGLE FOR Italian- -Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023, experts from five countries recounted several points about the paradigms of cardiological and cardiometabolic care for better control of classical modifiable risk factors in the year 2023. It is believed herein, that the need to intensify treatment, actively search for patients with cardiovascular risk factors, especially with arterial hypertension, hypercholesterolemia and diabetes, should go hand in hand with the implementation of the latest therapy, based on single pill combinations including proven, effective antihypertensive, lipid-lowering and antidiabetic molecules, many of which are listed in the present document. There is a need to use both new technological concepts, completely new drugs, as well as novel treatment concepts such as metabolic treatment in coronary artery disease, try to intensify the fight against smoking in every way, including the available range of drugs and procedures reducing the harm. This approach will provide substantially better control of the underlying cardiovascular risk factors in countries as varied as Italy, Poland, Spain, Uzbekistan and Vietnam.

Cardiovascular toxicity of checkpoint inhibitors: review of associated toxicity and design of the Spanish Immunotherapy Registry of Cardiovascular Toxicity.

Immune checkpoint inhibitors (ICI) have changed the prognosis of many tumors. However, concerning associated cardiotoxicity has been reported. Little is known about the real-life incidence-specific surveillance protocols or the translational correlation between the underlying mechanisms and the clinical presentation of ICI-induced cardiotoxicity. The lack of data from prospective studies led us to review the current knowledge and to present the creation of the Spanish Immunotherapy Registry of Cardiovascular Toxicity (SIR-CVT), a prospective registry of patients receiving ICI that aims to examine the role of hsa-miR-Chr8:96, (a specific serum biomarker of myocarditis) in the early diagnosis of ICI-induced myocarditis. An exhaustive prospective cardiac imaging study will be performed before and during the first 12 months of treatment. The correlation between clinical, imaging, and immunologic parameters may improve our understanding of ICI-induced cardiotoxicity and enable simpler surveillance protocols. We assess ICI-induced cardiovascular toxicity and describe the rationale of the SIR-CVT.

Use of rivaroxaban attenuates renal function impairment in patients with atrial fibrillation: insights of the EMIR study.

BACKGROUND: In atrial fibrillation (AF) patients on vitamin K antagonists, a progressive deterioration of renal function is common but there is limited evidence with long-term use of rivaroxaban. Herein, we investigated the change in renal function in AF patients after 2 years of rivaroxaban treatment. METHODS: The EMIR registry is an observational and multicentre study including AF patients treated with rivaroxaban for at least 6 months prior to inclusion. Changes in analytical parameters were recorded during 2 years of follow-up. Renal function was estimated using the Cockroft-Gault equation. RESULTS: 1433 patients (638, 44.5% women, mean age of 74.2 ± 9.7 years) were included. Creatinine clearance (CrCl) was available at baseline and at 2 years in 1085 patients. At inclusion, 33.2% of patients had impaired renal function (CrCl <60 ml/min). At 2 years, we were not able to find changes in the proportion of patients with impaired renal function, which increased to 34.6% (p = 0.290). However, the baseline mean CrCl was 76.0 ± 30.5 ml/min and slightly improved at 2 years (77.0 ± 31.8 ml/min; p = 0.014). Overall, the proportion of patients with CrCl <60 ml/min at baseline that had CrCl ≥60 ml/min at 2 years was significantly higher compared to that of patients with CrCl ≥60 ml/min at baseline and CrCl <60 ml/min after (22.2% vs. 13.1%; p < 0.001) CONCLUSIONS: In AF patients on long-term rivaroxaban therapy, a decrease in renal function was not observed. We even observed a slight improvement in the patients with renal impairment. These results reinforce the idea that rivaroxaban may be a safe option even in patients with renal impairment.

Lipid management across Europe in the real-world setting: a rapid evidence review.

OBJECTIVE: To provide a contemporary overview of recent real-world lipid-lowering therapy (LLT) practices and outcomes in patients with hypercholesterolemia/dyslipidemia at high/very high risk of atherosclerotic cardiovascular disease in Europe. METHODS: A structured literature review of recent (July 2015-July 2020) real-world studies reporting lipid management and outcomes was conducted using a rapid evidence synthesis. Outcomes included patient characteristics, LLT treatment practices, adherence and low-density lipoprotein cholesterol (LDL-C) goal attainment. RESULTS: Fifty-three real-world observational studies in high/very high risk patients were selected after screening 5664 records (n = 50 national [sample size range 38-237,279] and n = 3 multinational studies [sample size range 6648-8456]). Mean age ranged from 33 to 77 years; hypertension, diabetes and obesity were commonly reported comorbidities. Statins were the most common LLT; patients without familial hypercholesterolemia (FH) mostly received high or moderate intensity statins/LLT, while patients with FH mostly received high intensity statins/LLT. The proportion of patients receiving ezetimibe was low overall (ezetimibe + statin use in those with and without familial hypercholesterolemia [FH] range 5%-59% and 1%-22%, respectively). Overall, the use of proprotein convertase subtilisin/kexin 9 inhibitor (PCSK9i) therapy was limited. Adherence to LLT therapies was defined variably and ranged from 46%-92%. LDL-C goal attainment was suboptimal, irrespective of LLT (overall range in goal attainment with oral LLT was 2%-73% [FH: 2%-23%] and with PCSK9i was 20%-65%). CONCLUSIONS: LDL-C control is suboptimal and the available LLT armamentarium, most importantly combination therapy, is being underutilized in high/very high risk patients leading to inadequate management of cardiovascular risk.

First national registry on the effectiveness and safety of evolocumab in clinical practice in patients attended in cardiology in Spain. The RETOSS-CARDIO study. / Primer registro nacional sobre la efectividad y seguridad de evolocumab en la práctica clínica en pacientes atendidos en cardiología en España. Estudio RETOSS-CARDIO.

OBJECTIVE: To present the first registry used to analyse the clinical profile of patients treated with evolocumab in Spain, including the effectiveness on the lipid profile and safety in the «real world¼ setting. METHODS: Multicentre, retrospective, and observational study of patients starting treatment with evolocumab from February 2016 to May 2017 in clinical practice in Spanish cardiology units. RESULTS: A total of 186 patients (mean age 60.3 ± 9.8 years were included, 35.5% with familial hypercholesterolaemia, and 94.1% with a previous cardiovascular event) from 31 cardiology units. Baseline lipid profile: Total cholesterol 219.4 ± 52.2 mg/dL, LDL-cholesterol 144.0 ± 49.0mg/dL, HDL-cholesterol 47.7 ± 13.0mg/dL, and triglycerides 151.0 ± 76.2mg/dL. At the time of initiating evolocumab, 53.8% of patients were taking statins (50% had partial or total intolerance to statins), and 51.1% ezetimibe. In all cases, the dose of evolocumab used was 140 mg, mainly every 2 weeks (97.3%). Evolocumab compliance was high (92.3%). Treatment with evolocumab was interrupted in 6 patients (3.2%), with only 1 (0.5%) due to a probable side effect. Evolocumab significantly reduced total cholesterol (30.9% at week 2, and 39.3% at week 12; P<.001), LDL cholesterol (44.4% and 57.6%, respectively; P<.001), and triglycerides (14.8% and 5.2%, respectively; P<001), with no significant changes in HDL-cholesterol (6.7% and 2.0%; P=.14). CONCLUSIONS: In clinical practice, evolocumab is associated with reductions in LDL cholesterol, with nearly 60% after 12 weeks of treatment, and with low rates of interruptions due to side effects and high medication compliance. These results are consistent with those reported in randomised clinical trials.

Edoxaban for the prevention of stroke in patients with atrial fibrillation.

INTRODUCTION: Edoxaban is the last direct oral anticoagulant marketed for the prevention of stroke among patients with nonvalvular atrial fibrillation (AF). Areas covered: ENGAGE AF-TIMI 48 was the pivotal clinical trial that led to the approval of edoxaban 60 mg once daily. After the publication of this study, a great number of substudies and post hoc analyses have been published, together with some observational studies. The aim of this review was to update the current evidence about the use of edoxaban in AF patients. Expert opinion: In the ENGAGE AF-TIMI 48 trial, edoxaban 60 mg was noninferior to warfarin for the prevention of stroke or systemic embolism, but significantly reduced the risk of bleeding, major adverse cardiac events and death from cardiovascular causes. The relative efficacy and safety of edoxaban 60 mg compared with warfarin were independent of different clinical conditions, such as prior stroke, age, risk of falls, renal function, hepatic disease, ischemic heart disease, heart failure, valvular heart disease, or cancer. Data about the effectiveness and safety of edoxaban in real-life patients are scarce, but consistent with those of the pivotal clinical trial. Edoxaban seems a cost-effective alternative to warfarin among AF patients with moderate to high thromboembolic risk.

Influence of renal function on anticoagulation control in patients with non-valvular atrial fibrillation taking vitamin K antagonists.

BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) has been related to poor anticoagulation control and an increased risk of bleeding. This study aims to evaluate the association between impaired renal function (eGFR <60 mL/min/1.73 m2 ) and anticoagulation control in patients with non-valvular atrial fibrillation (AF) on vitamin K antagonists (VKA) therapy. We also assessed whether the predictive value of the SAMe-TT2 R2 score prevailed for subgroups both with and without CKD. METHODS: This is an ancillary analysis of 1381 patients from the PAULA study, which was a cross-sectional, retrospective and nationwide multicenter study. RESULTS: A total of 370 patients had eGFR <60 mL/min/1.73 m2 . Anticoagulation control levels progressively worsened across each stage of CKD. Multiple linear regression analysis showed CKD as an independent predictor of time in therapeutic range (TTR). In the subgroup of patients with preserved renal function, female sex, diet affecting INR, polypharmacy and amiodarone were associated with poorer TTR. The SAMe-TT2 R2 score had a significant but modest predictive value for TTR<65% (AUC, area under the curve 0.558, P = .002). In the subgroup of patients with CKD, the SAMe-TT2 R2 (>2 points) showed no significant predictive capacity for TTR (AUC 0.528, P = .354). The average TTR was similar for both sexes (P = .255), but with a higher percentage of males subjects with TTR ≥65% (P = .013). CONCLUSION: Chronic kidney disease is associated with poor anticoagulation control in patients with non-valvular AF taking VKA. The SAMe-TT2 R2 score was not predictive of poor TTR in the subgroup with CKD, although a modest predictive value for poor TTR was found in those without CKD.

Diabetes mellitus and cardiovascular clinical characteristics of Spanish women with stable ischaemic heart disease: Data from the SIRENA study.

The relationship between diabetes and the cardiovascular clinical characteristics of Spanish women with stable ischaemic heart disease was studied in a nationwide cross-sectional study. Diabetes was related to a higher burden of risk factors, comorbidity, multivessel disease and coronary surgery.

Usefulness of a Cardiovascular Polypill in the Treatment of Secondary Prevention Patients in Spain: A Cost-effectiveness Study.

INTRODUCTION AND OBJECTIVES: To estimate the health benefits and cost-effectiveness of a polypill intervention (aspirin 100 mg, atorvastatin 20 mg, ramipril 10 mg) compared with multiple monotherapy for secondary prevention of cardiovascular events in adults with a history of myocardial infarction from the perspective of the Spanish National Health System. METHODS: An adapted version of a recently published Markov model developed and validated in Microsoft Excel was used to compare the cost-effectiveness of the polypill with that of its combined monocomponents over a 10-year time horizon. The population included in the model had a mean age of 64.7 years; most were male and had a history of myocardial infarction. The input parameters were obtained from a systematic literature review examining efficacy, adherence, utilities, and costs. The results of the model are expressed in events avoided, incremental costs, incremental life years, incremental quality-adjusted life years, and the incremental cost-effectiveness ratio. RESULTS: Over a 10-year period, use of the cardiovascular polypill instead of its monocomponents simultaneously would avoid 46 nonfatal and 11 fatal cardiovascular events per 1000 patients treated. The polypill would also be a more effective and cheaper strategy. Probabilistic analysis of the base case found a 90.9% probability that the polypill would be a cost-effective strategy compared with multiple monotherapy at a willingness-to-pay of 30 000 euros per quality-adjusted life year. CONCLUSIONS: The polypill would be a cost-effective strategy for the Spanish National Health System with potential clinical benefits.

[Delphi consensus on management of dyslipidaemia in patients with impaired glucose metabolism: Diana study]. / Consenso Delphi sobre el manejo de la dislipidemia en pacientes con alteración del metabolismo de la glucosa: estudio Diana.

OBJECTIVES: The aim of the present study was to develop a multidisciplinary consensus based on the Delphi system to establish clinical recommendations for the management of dyslipidaemia when hyperglycaemia is present, and the relevant factors that should be taken into consideration when prescribing and monitoring treatment with statins. METHODS: The questionnaire developed by the scientific committee included four blocks of questions about dyslipidaemia in patients with impaired glucose metabolism. The results of the first two blocks are presented here: a) management of dyslipidaemia; b) relevant factors that should be taken into consideration when prescribing and monitoring treatment with statins. RESULTS: Among the 497 experts who participated in the study, an agreement of over 90% was attained for recommending screening for dyslipidaemia in patients with diabetes or pre-diabetes and/or cardiovascular disease or a family history and/or abdominal obesity and/or hypertension. There was a high degree of agreement that a statin is the lipid-lowering treatment of choice, and that it should be switched when side effects develop. Also, the choice of statin and dose should be made according to baseline LDL cholesterol levels, the target to achieve, and the possible drug-drug interactions. CONCLUSIONS: The screening of dyslipidaemia is primarily conducted in patients with cardiovascular disease, or any major cardiovascular risk factor. When prescribing a statin, physicians mainly focus on the ability to reduce LDL cholesterol and the risk of drug interactions.

Improving cardiovascular protection: focus on a cardiovascular polypill.

Lack of adherence may explain, at least in part, the poor cardiovascular risk factors control observed in patients with ischemic heart disease, increasing the risk of developing new events. Polypill improves medication adherence, which may actually reduce blood pressure and LDL cholesterol compared with the drugs given separately. The fixed combination of acetylsalicylic acid 100 mg + ramipril 2.5, 5, or 10 mg + either simvastatin 40 mg or atorvastatin 20 mg is the unique cardiovascular polypill that has been registered in 22 countries worldwide. The polypill-containing simvastatin has been specifically tested in a clinical trial including only patients with ischemic heart disease. The FOCUS study showed that patients treated with the polypill showed a higher adherence compared with those receiving separate medications.

An evaluation of the latest evidence relating to renin-angiotensin system inhibitors.

INTRODUCTION: In the last few years, a number of important clinical trials have been completed that have investigated the inhibition of the renin-angiotensin system. New drugs, focusing on this system, have now emerged as a result. AREAS COVERED: The authors review the most relevant information available, reported from the last 5 years, pertaining to the most important clinical trials on renin-angiotensin system blockers (ARBs). The authors' data review includes the trials of aliskiren, telmisartan, olmesartan and azilsartan. The authors also review the possible risk of cancer with ARBs. EXPERT OPINION: The results of ASPIRE and ALTITUDE trials strongly suggested that dual inhibition of aliskiren with either ARBS or angiotensin converting enzyme inhibitors (ACEi) should be avoided. Olmesartan is an effective and safe antihypertensive agent, but special attention should be paid to high-risk patients, such as those with coronary disease, to avoid an excessive reduction in blood pressure. The authors also note that while azilsartan is probably the most potent ARB, there is still a lack of data regarding potential organ damage and the incidence of cardiovascular events. Lastly, recent evidence has shown a lack of a relationship between ARB therapy and the occurrence of cancer.

[Blood pressure control in hospital units in Spain]. / Control de la presión arterial en unidades hospitalarias de referencia en España.

BACKGROUND AND OBJECTIVE: Blood pressure (BP) control has been extensively studied in patients attended in primary care but reports in the hospital setting, which includes referral units, are scarce. The aim was to evaluate the degree of BP control in hypertensive patients attended in referral units. PATIENTS AND METHODS: We studied 1,550 hypertensive subjects (41.5% women) with a mean age of 64 (12) years, who were receiving antihypertensive drugs. The degree of BP control was estimated in a single visit by the proportion of patients with BP below 140/90 mm Hg. RESULTS: BP was controlled in 653 patients (42%). In comparison, those whose BP was not controlled were more frequently women (odds ratio [OR] 1.57; 95% confidence interval [95%CI]: 1.23-1.99), obese (OR 1.28; 95%CI 1.00-1.63), smokers (OR 1.78; 95%CI 1.36-2.34), had left ventricular hypertrophy (OR 1.86; 95%CI 1.46-2.36) and elevated values of total serum cholesterol (OR 1.50; 95%CI 1.19-1.90) and triglycerides (OR 1.63; 95%CI 1.29-2.07). Therapeutical inertia was observed in 39% of uncontrolled patients. In a subgroup of patients who underwent ambulatory BP monitoring, discordance between measurements was only present in 23% (9.8 with isolated clinic hypertension and 13.1% with masked hypertension). CONCLUSION: The degree of BP control in patients attended in referral units is estimated in 42% and has not been modified in the last decade. Although therapeutical effort and inertia have improved, this only compensates the increased risk and comorbidities of attended patients, making more difficult the control of BP values.

Blood pressure control with angiotensin receptor blocker-based three-drug combinations: key trials.

INTRODUCTION: Most hypertensive patients only achieve blood pressure (BP) control with a combination of antihypertensive drugs from different classes and many require three or more drugs. Two three-drug, fixed-dose combinations are available: (1) the angiotensin receptor blocker (ARB), valsartan (VAL), the calcium channel blocker, amlodipine (AML), and the diuretic, hydrochlorothiazide (HCTZ); (2) the ARB, olmesartan medoxomil (OLM), AML, and HCTZ. METHODS: This article reviews two clinical studies in patients with moderate-to-severe hypertension, which compared the efficacy and safety of VAL/AML/HCTZ and OLM/AML/HCTZ with the component two-drug combinations. RESULTS: Each triple combination produced significantly greater reductions in seated systolic/diastolic BP and higher BP control rates than the two-drug combinations. Subgroup analyses showed that BP reductions and control rates with the three-drug combinations were unaffected by age, gender, race, and hypertension severity (VAL/AML/HCTZ and OLM/AML/HCTZ), and that efficacy was maintained for up to 52 weeks (OLM/AML/HCTZ). OLM/AML/HCTZ and VAL/AML/HCTZ also produced significantly larger reductions in ambulatory systolic and diastolic BP over 24 hours, the daytime, and nighttime compared with two-drug combinations. Adverse events were mainly of mild or moderate intensity and each threedrug combination was well tolerated. CONCLUSION: ARB/AML/HCTZ combinations produce BP reductions and control rates superior to two-drug combinations and may help difficult-to-treat patients to achieve BP control.

Prevalence of left-ventricular hypertrophy by multiple electrocardiographic criteria in general population: Hermex study.

OBJECTIVES: To determine the prevalence of left-ventricular hypertrophy (LVH) in the general population by means of multiple electrocardiographic criteria and those variables independently associated. METHODS: Random-sample cross-sectional study of the general population aged between 25 and 79 years, representative of a health area, was conducted. An electrocardiogram was recorded 'on line' in the Electropres project website; 17 LVH criteria together with two combined criteria were used. By multivariate analysis we examined those variables independently associated with the presence of electrocardiographic LVH. RESULTS: We recruited 2564 individuals, mean age 50.9 [standard deviation (SD) 14.7] years, 45.7% men. The criteria more prevalent were: Dalfó 19.4%, RV6/V5 14.5%, Perugia 10.9%, any combination with at least three positive criteria (Combined 3) 9.4%, Romhilt 7.5%, Lewis 6.2% and the recommended criteria of the European Society of Hypertension 4%. The best prevalence ratio between hypertensive and normotensive individuals was achieved with Lewis, Dalfó and Perugia criteria. The least prevalence was Sokolow 0.7%. The variables that were independently associated with the presence of LVH by Combined 3 criterion were pulse pressure at least 50 [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.47-3.09], arterial hypertension (OR 1.75, 95% CI 1.21-2.53) and smoking (OR 0.69, 95% CI 0.50-0.95). CONCLUSIONS: The detection ability of the electrocardiogram with regard to the LVH may improve with the use of other criteria than those currently recommended by the guidelines. The presence of LVH is positively associated with hypertension and elevated pulse pressure and negatively with a history of smoking.

Clinical profile and management of patients with chronic ischemic heart disease according to age in the population daily attended by cardiologists in Spain The ELDERCIC study.

OBJECTIVES: This study was aimed to evaluate the differences according to age in the clinical profile and management of outpatients with chronic ischemic heart disease attended by cardiologists in Spain. METHODS: Patients with an established diagnosis of chronic ischemic heart disease were included in this cross-sectional multicenter study. The age of 65 years was considered as the cut-off point for the present analysis. RESULTS: A total of 1038 subjects were included, 524 of them (50.5%) >65 years. Patients >65 years had a lesser prevalence of smoking, a longer history of hypertension, a worse left ventricular ejection fraction and a higher prevalence of heart failure and renal insufficiency than younger subjects. The number of prescribed drugs was higher in patients >65 years (6.1+/-1.9 vs 5.7+/-2.1, p=0.004). Blood pressure control rate was lower in older patients (38.1% vs 46.5%, p=0.008). No significant differences were found either in LDL-cholesterol (42.4% vs 46.5%), or glycemic control rates (42.4% vs 41.4%), both p=NS. Diagnostic and therapeutic procedures were also compared in >65 vs < or =65 years, exercise test was performed in 51.5% vs 62.8% (p<0.0001); stress echocardiography in 18.3% vs 13.2% (p=0.027); coronary angiography in 38.6% vs 53.5% (p<0.0001); and coronary revascularization in 37.2% vs 46.9% (p=0.002), without significant differences in electrocardiogram, echocardiogram, or isotopic exams. CONCLUSIONS: Older patients exhibited a worse clinical profile and a worse blood pressure control rate than the younger. However, diagnostic and therapeutic procedures appear to be frequently underused in the old patients.