José Francisco Kerr Saraiva

I Diretriz de Prevenção Cardiovascular da Sociedade Brasileira de Cardiologia - Resumo Executivo

Brazil currently faces a major health challenge: the pandemic scenario of cardiovascular morbidity and mortality. According to Brazilian Health Ministry data, 326,000 deaths due to cardiovascular diseases (CVD) occurred in 2010, corresponding to approximately 1,000 deaths/day, 200,000 deaths due exclusively to ischemic heart and cerebrovascular diseases, reflecting a gloomy scenario far from the minimally acceptable control.

Atorvastatin for high-risk statin-naïve patients undergoing noncardiac surgery: The Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD) randomized trial

Background Preliminary evidence suggests that statins may prevent major perioperative vascular complications. Methods We randomized 648 statin‐naïve patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80 mg anytime within 18 hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12 hours after the surgery, and then 40 mg/d (or placebo) for 7 days. The primary outcome was a composite of all‐cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30 days. Results The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group (hazard ratio [HR] 0.87, 95% CI 0.60‐1.26, P = .46). No significant effect was observed on the 30‐day secondary outcomes of all‐cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53‐2.47, P = .74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35‐1.68, P = .50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53‐1.19, P = .26), and stroke (0.9% vs 0%, P = .25). Conclusion In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short‐term perioperative course of statin in statin‐naïve patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high‐risk statin‐naïve patients is feasible and should be done to definitely establish the efficacy and safety of statin in this patient population.

Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial

Importance The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain. Objective To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. Design, Setting and Participants We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. Interventions Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. Main Outcomes and Measures The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days. Results The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, −0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, −0.18%; 95% CI, −0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57). Conclusions and Relevance In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days. Trial Registration clinicaltrials.gov Identifier: NCT02298088

Combination of amlodipine and enalapril in hypertensive patients with coronary disease

FUNDAMENTO: Pacientes (pts) com doenca coronariana (DAC) estavel podem se beneficiar de menor pressao arterial (PA), conforme estudos recentes. OBJETIVO: Avaliar a eficacia e a tolerabilidade da combinacao fixa anlodipino + enalaprila, comparada a anlodipino na normalizacao da PA diastolica (PAD) ( 90 e 110 mmHg durante o wash-out de quatro semanas, em uso so de atenolol. Apos wash-out randomizamos para combinacao (A) ou anlodipino (B) e seguimos de quatro em quatro semanas ate 98 dias. As doses (mg) iniciais foram, respectivamente: A- 2,5/10 e B- 2,5, sendo incrementadas se PAD> 85mmHg, nas visitas. Estatistica com χ2, Fischer e analise de variância, para p< 0,05. RESULTADOS:de 110 pts selecionados, randomizamos 72 (A= 32, B= 40). As reducoes da PAD e da PA sistolica (PAS) foram intensas (p< 0,01), mas sem diferencas entre os grupos em mmHg: PAS, A (127,7 ± 13,4) e B (125,3 ± 12,6) (p= 0,45) e PAD, A (74,5 ± 6,7 mmHg) e B (75,5 ± 6,7 mmHg) (p= 0,32). Houve menos edema de membros inferiores no A (7,1% vs 30,6%, p=0,02) no 98o dia. CONCLUSAO: A combinacao fixa de enalaprila com anlodipino, tal qual anlodipino isolado, em pts com DAC e HAS estagios I e II foi eficaz na normalizacao da pressao, adicionando bloqueio ao sistema renina-angiotensina.BACKGROUND Patients (pts) with stable coronary artery disease (CAD) can benefit from a decrease in the blood pressure (BP), according to recent studies. OBJECTIVE To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP) (<85 mmHg), in pts with CAD and systemic arterial hypertension (SAH). METHODS Double-blind and randomized study, with two groups of pts with DAP > or =90 and <110 mmHg and CAD. Patients with left ventricular ejection fraction (LVEF) < 40%, symptoms of heart failure or angina class III and IV, severe diseases and DAP > or =110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A) or amlodipine (B) and were followed every four weeks up to 98 days. The initial doses (in mg) were, respectively: A- 2.5/10 and B- 2.5; the doses were increased when DAP > 85mmHg, at the visits. Statistical analysis was carried out with chi2, Fischer and analysis of variance, for p< 0.05. RESULTS Of the 110 selected pts, 72 (A= 32, B= 40) were randomized. The decreases in DAP and systolic arterial pressure (SAP) were significant (p< 0.01), but with no difference between the groups in mmHg: SAP, A (127.7 +/- 13.4) and B (125.3 +/- 12.6) (p= 0.45) and DAP, A (74.5 +/- 6.7 mmHg) and B (75.5 +/- 6.7 mmHg) (p= 0.32). Group A presented a lower incidence of lower-limb edema: (7.1% vs 30.6%, p=0.02) on the 98th day of follow-up. CONCLUSION The fixed combination of enalapril and amlodipine, as well as isolated amlodipine, was effective in the normalization of BP in pts with CAD and SAH stages I and II, adding blockage of the renin-angiotensin system.

Estatinas na doença renal crônica

Hipertrigliceridemia e o HDL baixo sao aspectos comuns em pacientes com insuficiencia renal cronica. A mortalidade cardiovascular esta substancialmente aumentada na presenca de doenca renal cronica (10-20 vezes maior). Existem evidencias de estudos clinicos com estatinas sugerindo uma acao protetora dessas drogas na progressao da doenca renal. Alem disso, pacientes pos-transplante renal recebendo fluvastatina, experimentaram reducao na incidencia de infartos nao fatais e de mortalidade cardiaca. Entretanto, um estudo recente com atorvastatina nao demonstrou reducoes na morbi-mortalidade cardiovascular entre pacientes diabeticos em hemodialise. Estudos em andamento definirao o preciso papel das estatinas neste grupo especial de pacientes.

Ticagrelor versus Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: Rationale and Design of the TicagRElor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial

Background The safety and efficacy of ticagrelor in patients with ST‐elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain. Objectives The primary objective of the TicagRElor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short‐term safety of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of ticagrelor compared with clopidogrel at 12‐months. Design The TREAT trial is a multicenter, randomized, phase III, Prospective randomized open blinded end‐point (PROBE) study that enrolled 3,799 patients in 152 sites from 10 countries. Following administration of fibrinolytic therapy patients were randomized to a loading dose of ticagrelor 180 mg or clopidogrel 300 mg followed by a maintenance dose of ticagrelor 90 mg twice daily or clopidogrel 75 mg/day for 12‐months. The primary outcome is the rate of TIMI major bleeding at 30‐days and will be assessed for non‐inferiority using an intention‐to‐treat analysis. Co‐treatments include aspirin and anticoagulants. Other evidence based therapies are also recommended. Secondary efficacy outcome include a composite of death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic event. All‐cause mortality as well as individual components of the combined efficacy endpoint will also be ascertained. Summary TREAT is an international randomized controlled trial comparing ticagrelor with clopidogrel in STEMI patients treated with fibrinolytic therapy. The results of this trial will inform clinical practice and international guidelines.

Tratamento da hipertensão arterial com olmesartana medoxomila em escalonamento

BACKGROUND: The national and international guidelines emphasize the importance of the effective treatment of essenssial hypertension. Nevertheless, low levels of control are observed, as well as low attainment of the recommended goals, indicating that it is important to plan and implement better treatment strategies. OBJECTIVE: To evaluate the efficacy of a based treatment algorithm with olmesartan medoxomil. METHODS: This is an open, national, multicentric and prospective study of 144 patients with primary arterial hypertension, stages 1 and 2, naive to treatment or after a 2-to-3 week washout period for those in whom treatment was ineffective. The use of olmesartan medoxomil was assessed in a treatment algorithm divided into 4 phases: (i) monotherapy (20 mg), (ii-iii) associated to a hydrochlorothiazide (20/12.5 mg and 40/25 mg) and (iv) addition of amlodipine besylate (40/25 mg + 5 mg). RESULTS: At the end of the phased-treatment, 86% of the study subjects attained the goal of BP 20 mmHg) and of diastolic responders (DAP > 10 mmHg) was 87.5% and 92.4%, respectively. CONCLUSION: The study was based on a treatment regimen that was similar to the therapeutic approach in daily clinical practice and showed that the use of olmesartan medoxomil in monotherapy or in association with hydrochlorothiazide and amlodipine was effective in the attainment of the recommended goals for hypertension stage 1 and 2 hypertensive individuals.

Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), &bgr;-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464–1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM)

BackgroundSince the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes.Main bodyThe Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy.ConclusionsDiabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.

Combinação de anlodipino e enalaprila em pacientes hipertensos com doença coronariana

FUNDAMENTO: Pacientes (pts) com doenca coronariana (DAC) estavel podem se beneficiar de menor pressao arterial (PA), conforme estudos recentes. OBJETIVO: Avaliar a eficacia e a tolerabilidade da combinacao fixa anlodipino + enalaprila, comparada a anlodipino na normalizacao da PA diastolica (PAD) ( 90 e 110 mmHg durante o wash-out de quatro semanas, em uso so de atenolol. Apos wash-out randomizamos para combinacao (A) ou anlodipino (B) e seguimos de quatro em quatro semanas ate 98 dias. As doses (mg) iniciais foram, respectivamente: A- 2,5/10 e B- 2,5, sendo incrementadas se PAD> 85mmHg, nas visitas. Estatistica com χ2, Fischer e analise de variância, para p< 0,05. RESULTADOS:de 110 pts selecionados, randomizamos 72 (A= 32, B= 40). As reducoes da PAD e da PA sistolica (PAS) foram intensas (p< 0,01), mas sem diferencas entre os grupos em mmHg: PAS, A (127,7 ± 13,4) e B (125,3 ± 12,6) (p= 0,45) e PAD, A (74,5 ± 6,7 mmHg) e B (75,5 ± 6,7 mmHg) (p= 0,32). Houve menos edema de membros inferiores no A (7,1% vs 30,6%, p=0,02) no 98o dia. CONCLUSAO: A combinacao fixa de enalaprila com anlodipino, tal qual anlodipino isolado, em pts com DAC e HAS estagios I e II foi eficaz na normalizacao da pressao, adicionando bloqueio ao sistema renina-angiotensina.BACKGROUND Patients (pts) with stable coronary artery disease (CAD) can benefit from a decrease in the blood pressure (BP), according to recent studies. OBJECTIVE To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP) (<85 mmHg), in pts with CAD and systemic arterial hypertension (SAH). METHODS Double-blind and randomized study, with two groups of pts with DAP > or =90 and <110 mmHg and CAD. Patients with left ventricular ejection fraction (LVEF) < 40%, symptoms of heart failure or angina class III and IV, severe diseases and DAP > or =110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A) or amlodipine (B) and were followed every four weeks up to 98 days. The initial doses (in mg) were, respectively: A- 2.5/10 and B- 2.5; the doses were increased when DAP > 85mmHg, at the visits. Statistical analysis was carried out with chi2, Fischer and analysis of variance, for p< 0.05. RESULTS Of the 110 selected pts, 72 (A= 32, B= 40) were randomized. The decreases in DAP and systolic arterial pressure (SAP) were significant (p< 0.01), but with no difference between the groups in mmHg: SAP, A (127.7 +/- 13.4) and B (125.3 +/- 12.6) (p= 0.45) and DAP, A (74.5 +/- 6.7 mmHg) and B (75.5 +/- 6.7 mmHg) (p= 0.32). Group A presented a lower incidence of lower-limb edema: (7.1% vs 30.6%, p=0.02) on the 98th day of follow-up. CONCLUSION The fixed combination of enalapril and amlodipine, as well as isolated amlodipine, was effective in the normalization of BP in pts with CAD and SAH stages I and II, adding blockage of the renin-angiotensin system.