Factors associated with the discontinuation of evidence-based cardiovascular therapies in patients with stable coronary artery disease: a primary care perspective.

BACKGROUND: To identify factors associated with the discontinuation of evidence-based cardiovascular therapies after hospital discharge for a coronary event. DESIGN: Cross-sectional study carried out between June and October 2004 in 1799 primary care centers throughout Spain. PATIENTS AND METHODS: Eight thousand eight hundred and seventeen patients (73.7% males; 65.4 years) admitted for coronary disease causes in the past 6 months to 10 years and attending primary care postdischarge from hospital. Current medications, those prescribed at hospital discharge, and the development of adverse events, new risk factors, and comorbidities during follow-up, were collected from clinical records. RESULTS: After a median follow-up of 37.4 months, discontinuation rate of lipid-lowering agents, angiotensin renin system blockers, antiplatelet drugs, and beta-blockers were 7.2, 9.1, 10, and 20%, respectively. Of these, 10.8, 16.5, 9.9, and 20.1%, respectively, were because of adverse events. Factors associated with the discontinuation of lipid-lowering agents were the development of hypertension and diabetes during the follow-up. Discontinuation of antiplatelet drug was associated with an earlier history, or with de-novo occurrence, of atrial fibrillation. Discontinuation of angiotensin renin system blockers was associated with the development of atrial fibrillation, diabetes and hypercholesterolemia, and discontinuation of beta-blockers with de-novo appearance of peripheral artery disease, cerebrovascular disease, and heart failure. CONCLUSION: In patients followed-up in primary care, the discontinuation rate of cardiovascular disease medications was low and was mainly related to the development of adverse events together with new risk factors and comorbidities arising after hospital discharge.

Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects. / Riesgo cardiovascular residual de origen lipídico. Componentes y aspectos fisiopatológicos.

There is no doubt about the relationship between LDL-c and cardiovascular risk, as well as about the benefits of statin treatment. Once the objective of LDL-c has been achieved, the evidences that demonstrate the persistence of a high cardiovascular risk, a concept called residual risk, are notable. The residual risk of lipid origin is based on atherogenic dyslipidemia, characterized by an increase in triglycerides and triglyceride-rich lipoproteins, a decrease in HDL-c and qualitative alterations in LDL particles. The most commonly used measures to identify this dyslipidemia are based on the determination of total cholesterol, triglycerides, HDL, non-HDL cholesterol and remaining cholesterol, as well as apolipoprotein B100 and lipoprotein (a) in certain cases. The treatment of atherogenic dyslipidemia is based on weight loss and physical exercise. Regarding pharmacological treatment, we have no evidence of cardiovascular benefit with drugs aimed at lowering triglycerides and HDL-c, fenofibrate seems to be effective in situations of atherogenic dyslipidemia.

Non-HDL cholesterol as a therapeutic goal. / Colesterol-no HDL como objetivo terapéutico.

Although cholesterol linked to low-density lipoproteins (c-LDL) is well established as a risk factor for cardiovascular disease, there is often a more complex dyslipidaemia pattern that contributes to the formation of atherosclerotic plaque. Non-HDL cholesterol (c-NO-HDL) is used to estimate the total amount of atherogenic lipoproteins in plasma, some of which are not usually determined in daily clinical practice. c-NO-HDL is easily calculated from the subtraction of total plasma cholesterol from the cholesterol content carried by high density lipoproteins. The c-NO-HDL has a predictive value superior to that of C-LDL to estimate the risk of major cardiovascular events in epidemiological studies. Genetic studies by analysis of the complete genome, together with those based on Mendelian randomisation, point to the aetiological character of c-NO-HDL on ischaemic heart disease (IHD). Intervention studies, and the meta-analyses derived from them, close the causal circle between c-NO-HDL and IHD, by demonstrating that any intervention that decreases the concentrations of the former reduces the incidence of arteriosclerotic heart disease. The European ESC/EAS 2016 guide for the management of dyslipidaemia considers c-NO-HDL as a therapeutic target with a Class IIa recommendation (should be performed) Level B (data from a single randomised clinical trial [RCT]) or from several non-RCTs), and sets its target at less than 100 or 130mg/dL for those patients with very high risk or high risk, respectively. These achievable c-NO-HDL values are easily calculated by adding 30mg/dL to the c-LDL targets.

Fibrates in primary prevention of cardiovascular disease. Comments on the results of a systematic review of the Cochrane Collaboration. / Los fibratos en la prevención primaria de la enfermedad cardiovascular. Comentarios a los resultados de una revisión sistemática de la Colaboración Cochrane.

Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardial infarction, or non-fatal cerebrovascular accident (NNT: 112), and that reduce coronary morbidity and mortality by 21% (NNT: 125). In addition, fibrates could reduce previously established diabetic retinopathy. However, fibrates do not influence total mortality, or non-cardiovascular mortality. Its joint use with statins does not benefit patients without established cardiovascular disease, compared to the use of statins in monotherapy. Fibrates are safe, although they can elevate serum creatinine levels.

Fibrates in the secondary prevention of cardiovascular disease (infarction and stroke). Results of a systematic review and meta-analysis of the Cochrane collaboration. / Los fibratos en la prevención secundaria de la enfermedad cardiovascular (infarto e ictus). Resultados de una revisión sistemática y metaanálisis de la colaboración Cochrane.

Fibrates are a group of drugs that are known mainly for reducing triglycerides, increasing high density lipoproteins (HDL), and reducing the fraction of small, dense LDL particles. The results of a Cochrane Collaboration study have recently been published on their efficacy and safety in the secondary prevention of severe cardiovascular accidents, including coronary and cerebrovascular disease. The study included randomised clinical trials in which the fibrate was compared with placebo or with no treatment. Clinical trials comparing two different fibrates were excluded. The clinical trials evaluated included a total of 16,112 patients (13 trials). The meta-analysis (including all the trials with fibrates) showed evidence of a protective effect of the fibrates compared with placebo as regards a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin (hazard ration of 0.88, with a 95% confidence interval of 0.83 to 0.94; in 16,064 individuals included in 12 studies). Thus, the results showed, with a moderate level of evidence, that fibrates could be effective in secondary prevention considering a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (II). Tratamiento de la enfermedad del hígado graso no alcohólico.

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease. / Enfermedad del hígado graso no alcohólico, asociación con la enfermedad cardiovascular y tratamiento (I). Enfermedad del hígado graso no alcohólico y su asociación con la enfermedad cardiovascular.

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease.

Consensus document on the management of the atherogenic dyslipidaemia of the Spanish Society of Arteriosclerosis. / Documento de consenso sobre el manejo de la dislipemia aterogénica de la Sociedad Española de Arteriosclerosis.

Positioning document and summary of recommendations recently published by the Working Group on Atherogenic Dyslipemia of the Spanish Society of Arteriosclerosis and by the European Society of Arteriosclerosis.

The gap between dyslipidemia control perceived by physicians and objective control patterns in Spain.

OBJECTIVE: It is well-known that adequate control of dyslipidemia is low. But little is known about how well physicians perceive the control of their dyslipidemic patients. This study examines physicians' subjective perception of dyslipidemia control, and compares it with control determined objectively with published guidelines. METHODS: A total of 33,913 patients were studied cross-sectionally in 164 Spanish outpatients' clinics. Of these patients, 5583 were evaluable patients with a documented diagnosis of dyslipidemia. Control of dyslipidemia was evaluated by two methods: the physician's opinion on their patient's lipid levels (adequate control or inadequate control), and the proportion of patients who objectively reach the LDL-cholesterol goals of the National Cholesterol Education Program (NCEP/ATPIII). RESULTS: Physicians perceived that 44% (95% CI 42.7-45.3%) of their patients had an adequate control of their dyslipidemia, but only 32.8% (95% CI 31.6-34.0%) were objectively controlled. Subjective control hardly changed across the NCEP cardiovascular risk groups, but objective control was lower in the 2372 coronary heart disease patients (15.1%) and in the 1407 moderately high-risk patients (29.6%) than in the 1804 lower risk patients (58.5%). Physicians' perception of control was significantly and independently associated with objective control (P<0.001). CONCLUSIONS: Physicians overestimate dyslipidemia control in the majority of their patients. Misperception of control by physicians may contribute to the low achievement of objective control.

Evidence-based cardiovascular therapies and achievement of therapeutic goals in diabetic patients with coronary heart disease attended in primary care.

BACKGROUND: Diabetic patients have a higher rate of recurrent cardiovascular events and death than nondiabetic individuals. Although partially attributable to lower use of evidence-based preventive therapies, studies are lacking on the prescription rate during the stable phase of the disease. METHODS: Between June 1 and October 19, 2004, we obtained, from 1799 primary care centers throughout Spain, data on 8817 subjects (mean age 65.4 years, 73.7% male, 32.7% with diabetes) who had had a coronary event requiring hospitalization in the previous 6 months to 10 years. RESULTS: After adjustment for confounding variables, the diabetic patients received more frequent treatment with angiotensin-renin system blockers (73.5% vs 61%, P < .001), calcium channel blockers (29.8% vs 21.9%, P < .001), nitrates (58% vs 47.5%, P < .001), digoxin (6.6% vs 3.9%, P < .001), and diuretics (46.2% vs 32.2%, P < .001), but it is similar with respect to lipid-lowering drugs (81.1% vs 80.3%), antiplatelet drugs (80.2% vs 80.2%), or beta-blockers (45.4% vs 47.7%). The percentage of diabetic subjects attaining objectives for smoking habit, low-density lipoprotein cholesterol, blood pressure, and glycated hemoglobin were 90.7%, 29%, 38.2%, and 49.7%, respectively. Only 7% had optimum control of all their risk factors. The parameters most closely related to optimum treatment and risk-factor control were the specialist follow-up and the attending physician's awareness of appropriate treatment objectives. CONCLUSIONS: A significant percentage of diabetic patients with stable coronary disease receive evidence-based preventive medications in primary care. However, the percentage achieving adequate control of their risk factors is low and is related to the level of physician awareness of appropriate therapeutic targets.

[The real measurement of non-HDL-cholesterol: Atherogenic cholesterol]. / La auténtica dimensión del colesterol-no-HDL: colesterol aterogénico.

Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real measurement of atherogenic cholesterol. In addition, non-HDL-cholesterol do not show any variations between postprandial states. In fact, non-HDL-cholesterol should be an excellent marker of atherogenic cholesterol, and an major therapeutic target in patients with atherogenic dyslipidaemia. According with different clinical trials and with the epidemiological and mendelian studies, in patients with high cardiovascular risk, optimal level of cLDL will be under 70mg/dl, and under 100 ng/dl for non-HDL-cholesterol; and in high risk patients, 100mg/dl and 130mg/dl, respectively.

[Fibrates therapy: Rational use fenofibrate 2016. Executive summary]. / Terapia con fibratos: uso racional del fenofibrato 2016. Resumen ejecutivo.

To control lipid factors risk, beyond proper management of LDL cholesterol according to individual risk, detection and treatment of atherogenic dyslipidemia and abnormal levels of triglycerides or HDL cholesterol it should be considered for address a global cardiovascular protection, both in primary and secondary prevention. In this sense, these recommendations collect data on efficacy and safety about the combination statin with fibrates, often necessary for total control of dyslipidemia, particularly in patients with metabolic disorders such as diabetes mellitus, metabolic syndrome or visceral obesity. Reference to control and monitoring of treatment is also done, as well as benefits of fenofibrate not linked directly to their lipid-lowering effect.

[PREVENCAT study: control of cardiovascular risk in primary care]. / Estudio PREVENCAT: control del riesgo cardiovascular en atención primaria.

BACKGROUND AND OBJECTIVE: Most studies of cardiovascular risk factors (CVRF) conducted in our environment concentrate in a single CVRF. The PREVENCAT study was designed to estimate the control of CVRF in the population attended in primary care presenting arterial hypertension (HT), type 2 diabetes mellitus (DM2) and/or hypercholesterolemia (HC) as well as to assess the prevalence of Metabolic Syndrome in these patients. PATIENTS AND METHOD: Multicenter, cross-sectional study, in patients with HT, DM2 and/or HC, consecutively recruited by primary care physicians in Spain. The blood pressure, cholesterol, basal glycaemia, obesity, smoking and physical activity were assessed. The degree of control of these CVRF and the prevalence of MS were estimated. RESULTS: 2,649 patients were recruited, aged 64 (11.3) years, with a 51.6% of women. The most frequent diagnosis was HT (78.9%), followed by HC (58.4%) and DM2 (37.4%). In the whole sample, the percentages of patients who had a control or had initially normal values of blood pressure, cholesterol and basal glycemia were 40.0% (confidence interval [CI], 95% 38.2-41.9), 42.6% (95% CI, 40.5-44.7) and 62.7% (95% CI, 60.8-64.5), respectively. 15.6% of cases (95% CI, 14.3-17.0) had body mass index < or = 25 kg/m2; 87.5% were non-current smokers (95% CI, 86.2-88.8); and 46.2% practiced regular physical activity (95% CI, 44.3-48.1). 40% of patients had < or = 2 CVRF in good control. The prevalence of metabolic syndrome was 50.6% (95% CI, 48.7-52.5). CONCLUSIONS: The control of the CVRF considered in primary care attended population is insufficient. Hardly one of each 2 patients with HT, DM2 and HC is under control. The overweight and sedentarism control is still poorer.

[Tables of coronary risk evaluation adapted to the Spanish population: the DORICA study]. / Tablas de evaluación del riesgo coronario adaptadas a la población española. Estudio DORICA.

BACKGROUND AND OBJECTIVE: Independent risk factors (smoking, hypertension, hypercholesterolemia and diabetes mellitus) are direct causes of coronary heart disease and are common in the population. Considering all independent factors together seems to be more appropriate to estimate the global risk of coronary heart disease. The objective of this paper was to estimate the global risk of coronary heart disease based on the Framingham function, adapted to the prevalence of risk factors in Spain. SUBJECTS AND METHOD: The prevalence of risk factors in the Spanish population was estimated based on pooled analysis of regional cross-sectional random population surveys. Prevalence estimates and incidence rate of coronary events were replaced in the Framingham equation accordingly. Risk probability for 10 years was estimated and risk tables were designed using a gradual color coding system according to an increasing risk. RESULTS: The estimated attributable fraction (AF) for hypertension in the Spanish population was 26.7% for men and 22.9% women; that for hypercholesterolemia was 15.7% and 12.7% for men and women, respectively. Smoking was identified in the third position of the ranking order for males (AF 13.13%) and fourth for the female group (AF 3.71%). The prevalence of obesity was 13.2% for men and 17.5% for women. AF for obesity among men was 4% and it was 5% for women. CONCLUSIONS: An adaptation of the Framingham equation according to the prevalence of independent risk factors and incidence of coronary events in the Spanish population is useful to build instruments to estimate the 10-year global risk of coronary heart disease while a specific function based on a well-designed cohort study in not available in Spain.

[Achievement of therapeutic objectives]. / Consecución de objetivos terapéuticos.

Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk.

Variables associated with change in blood pressure control status after 1-year follow up in primary care: a retrospective analysis: the TAPAS study.

PURPOSE: This 1-year, retrospective, observational study assessed factors associated with changes in hypertension control status and differences in blood pressure (BP) management among general practitioners in Spain. METHODS: In 2009, 307 investigators from 260 primary care centres in Spain recruited the first four consecutive patients with hypertension that fit into one of four predefined cohorts: (1) uncontrolled BP at baseline and at a 1-year follow-up visit; (2) uncontrolled BP at baseline and good BP control at the 1-year follow-up visit; (3) good BP control at baseline and loss of BP control at the 1-year follow-up visit; and (4) good BP control at baseline and at the 1-year follow-up visit. RESULTS: A total of 1385 patients were included. Patients with poor BP and patients that lost BP control exhibited more cardiovascular risk factors. Although antihypertensive treatment was increased more markedly in these patients, this was not sufficient to attain/remain BP goals. Predictors for attaining BP control were no smoking, absence of diabetes, reduction in cholesterol, low baseline cholesterol, and no weight gain. Predictors for failing to maintain BP goals were weight gain, high baseline LDL cholesterol, and no reduction in fasting glucose. NSAID prescriptions increased markedly in patients that lost BP control compared to those that maintained BP control. CONCLUSION: Antihypertensive therapy should be intensified and healthy lifestyle changes should be emphasized, particularly weight control to improve BP control. Drugs that may increase BP levels, such as NSAIDs, should also be avoided.

[Risk of pharmacological interactions due to the co-administration of statins and cytochrome P450 isoenzyme 3A4-metabolized drugs: multicentre, crossover study]. / Riesgo de interacciones farmacológicas por la coadministración de estatinas con fármacos metabolizados por la isoenzima 3A4 del citocromo P450: estudio epidemiológico, transversal y multicéntrico.

BACKGROUND AND OBJECTIVES: Statins are safe but have a significant potential for pharmacological interactions. The objective of the study was to evaluate the prevalence of potential interactions throughout the cytochrome P450 isoenzyme 3A4 (CYP3A4) system in a large sample of statin-treated subjects and to determine which factors, from the patient and the physician, were associated with a higher risk of interactions. PATIENTS AND METHODS: This is an observational, cross-over, population study that included 7,880 subjects treated with statins. Both data from patients and from the1,681 participating physicians were recorded and analyzed. RESULTS: Fifty-nine percent of the participants were receiving a statin metabolized by the CYP3A4, and 21.5% of all participants received a drug, different from a statin, metabolized by the CYP3A4. There were no differences in the frequency of utilization of statins metabolized or not by the CYP3A4 in relation to the simultaneous prescription of drugs metabolized by the same pathway (22 vs. 21%, respectively). Globally, 12.9% of all participants were at risk of an interaction. These patients were older, received a higher number of drugs and had more comorbidity. Sixty percent of the physicians mentioned that the possibility of an interaction greatly conditioned their selection of a particular statin. Likewise, 56% of them had software that alerted of possible interactions. These aspects, however, did not influence the number of patients at risk of interactions. CONCLUSION: The proportion of statin-treated patients at risk of interaction is elevated. Physicians do not usually pay attention to this possibility despite having available alert software and therapeutic alternatives.

Gender differences in evidence-based pharmacological therapy for patients with stable coronary heart disease.

BACKGROUND: Women have a higher morbidity and mortality than men after an acute coronary event. We analyzed the prescription rates of evidence-based pharmacological therapies for patients with stable coronary heart disease and whether there were any differences with respect to gender. DESIGN: This cross-sectional study evaluated 8817 patients, 26.3% women, receiving attention from 1799 family doctors in primary care centers (PCC) throughout Spain, and who had had a coronary event requiring hospitalization in the previous 6 months to 10 years. RESULTS: Mean age was 65.4 years and a mean time-lapse since hospitalization of 37.4 months. In the overall population, prescription medications were: antiplatelet drugs in 80.5% of patients, 79% statins, 66% blockers of the angiotensin-renin system (BARS) and 47% beta-blockers. Males received less cardiovascular disease medications than females (4.3+/-1.5 versus 4.6+/-1.6, respectively; p<0.001), but when adjusted for risk factors the significance was lost (p=0.231). Following adjustment for risk factors and for co-morbidities, the use of diuretics was significantly higher in women while beta-blockers and statins were higher in men. The triple combination of antithrombotics, beta-blockers and statins was used in 41.4% (43.8% males versus 34.6% females; p<0.001) while 24.3% used this triple combination plus a BARS; without significant difference between the genders. CONCLUSIONS: An important percentage of patients with stable coronary disease, particularly women, attended-to in primary care do not receive medications that have been shown to decrease the morbido-mortality of cardiovascular disease.