Effects of a stepwise, structured LDL-C lowering strategy in patients post-acute coronary syndrome.

OBJECTIVE: Low-density lipoprotein cholesterol (LDL-C) lowering constitutes a cornerstone of secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet a considerable number of patients do not achieve guideline-recommended LDL­C targets. The 2016 European guidelines recommended titration of LDL­C lowering medication in a set number of steps, starting with oral medication. We aimed to investigate the effects of this stepwise approach in post-acute coronary syndrome (ACS) patients. METHODS: In a multicentre, prospective, non-randomised trial, we evaluated a three-step strategy aiming to reduce LDL­C to ≤ 1.8 mmol/l in post-ACS patients with prior ASCVD and/or diabetes mellitus. Steps, undertaken every 4-6 weeks, included: 1) start high-intensity statin (HIST); 2) addition of ezetimibe; 3) addition of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The primary outcome was the proportion of patients achieving LDL-C ≤ 1.8 mmol/l after Steps 1 and 2 (using oral medications alone). Secondary outcomes examined the prevalence of meeting the target throughout all steps ( https://onderzoekmetmensen.nl/nl/trial/21157 ). RESULTS: Out of 999 patients, 84% (95% confidence intervals (CI): 81-86) achieved the LDL­C target using only statin and/or ezetimibe. In an intention-to-treat analysis, the percentages of patients meeting the LDL­C target after each step were 69% (95% CI: 67-72), 84% (95% CI: 81-86), and 87% (95% CI: 85-89), respectively. There were protocol deviations for 23, 38 and 23 patients at each respective step. CONCLUSION: Through stepwise intensification of lipid-lowering therapy, 84% of very high-risk post-ACS patients achieved an LDL­C target of ≤ 1.8 mmol/l with oral medications alone. Addition of PCSK9i further increased this rate to 87% (95% CI: 85-89).

Impact of different anticoagulation management strategies on outcomes in atrial fibrillation: Dutch and Belgian results from the GARFIELD-AF registry.

BACKGROUND: The uptake rate of non-vitamin K oral anticoagulants (NOAC) for the treatment of non-valvular atrial fibrillation (AF) was far lower in the Netherlands (NL) compared to Belgium (BE). Also, patients on VKA in NL were treated with a higher target international normalized ratio (INR) range of 2.5 to 3.5. OBJECTIVES: To explore the effect of these differences on thromboembolism (TE) and bleeding. METHODS: Data from the GARFIELD-AF registry was used. Patients with new-onset AF and ≥1 investigator-determined risk factor for stroke were included between 2010 and 2016. Event rates from 2 years of follow-up were used. RESULTS: In NL and BE, 1186 and 1705 patients were included, respectively. Female sex (42.3% vs 42.2%), mean age (70.7 vs 71.3 years), CHA2 DS2 -VASc (3.1 vs 3.1), and HAS-BLED score (1.4 vs 1.5) were comparable between NL and BE. At diagnosis in NL vs BE, 72.1% vs 14.6% received vitamin K antagonists (VKA) and 17.8% vs 65.5% NOACs, varying greatly across cohorts. Mean INR was 2.9 (±1.0) and 2.4 (±1.0) in NL and BE, respectively. Event rates per 100 patient-years in NL and BE, respectively, of all-cause mortality (3.38 vs 3.90; hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15), ischemic stroke/TE (0.82 vs 0.72; HR 1.14, 95% CI 0.62-2.11), and major bleeding (2.06 vs 1.54; HR 1.33, 95% CI 0.89-1.99) did not differ significantly. CONCLUSIONS: In GARFIELD-AF, despite similar characteristics, patients on anticoagulants were treated differently in NL and BE. Although the rate of major bleeding was 33% higher in NL, variations in bleeding, mortality, and TE rates were not statistically significant.

Ticagrelor or prasugrel versus clopidogrel in elderly patients with an acute coronary syndrome: Optimization of antiplatelet treatment in patients 70 years and older--rationale and design of the POPular AGE study.

RATIONALE: Dual antiplatelet therapy with acetylsalicylic acid in combination with a more potent P2Y12- inhibitor (ticagrelor or prasugrel) is recommended in patients with acute coronary syndrome without ST-segment elevation (NSTE-ACS) to prevent atherothrombotic complications. The evidence on which this recommendation is based shows that ticagrelor and prasugrel reduce atherothrombotic events at the expense of an increase in bleeding events when compared with clopidogrel. However, it remains unclear whether ticagrelor or prasugrel has a better net clinical benefit in elderly patients with NSTE-ACS when compared with clopidogrel. The POPular AGE trial is designed to address the optimal antiplatelet strategy in elderly NSTE-ACS patients. STUDY DESIGN: POPular AGE is a multicenter, open-label, randomized controlled trial that aims to include 1000 patients ≥70years of age with NSTE-ACS. Patients are randomly assigned to receive either clopidogrel or a more potent P2Y12 inhibitor (ticagrelor or prasugrel). The first primary end point is any bleeding event requiring medical intervention. The second primary end point is the net clinical benefit, a composite of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, "PLATelet inhibition and patient Outcomes" major bleeding, or "PLATelet inhibition and patient Outcomes" minor bleeding. Patients will be followed for 1 year after randomization, and analyses will be performed on the basis of intention to treat. CONCLUSION: The POPular AGE is the first randomized controlled trial that will assess whether the treatment strategy with clopidogrel will result in fewer bleeding events without compromising the net clinical benefit in patients ≥70years of age with NSTE-ACS when compared with a treatment strategy with ticagrelor or prasugrel.

Infectious aortitis with multiple mycotic aneurysms caused by Streptococcus agalactiae.

We report a case of a 66-year-old man with multiple thoracoabdominal mycotic aortic aneurysms caused by Streptococcus agalactiae (S agalactiae). The infectious aortitis (IA) was diagnosed by transesophageal echocardiography and computed tomography and confirmed by positive blood cultures. The patient was treated with antibiotics, but, after worsening of the aortitis, a successful surgical procedure was performed. A review of the literature is presented together with a series of 7 other cases of IA caused by S agalactiae.

The predictive value of the exercise ECG for major adverse cardiac events in patients who presented with chest pain in the emergency department.

BACKGROUND: To improve early diagnostic and therapeutic decision making, we designed the HEART score for chest pain patients in the emergency department (ED). HEART is an acronym of its components: History, ECG, Age, Risk factors and Troponin. Currently, many chest pain patients undergo exercise testing on the consecutive days after presentation. However, it may be questioned how much diagnostic value the exercise ECG adds when the HEART score is already known. METHODS: A subanalysis was performed of a multicenter prospective validation study of the HEART score, consisting of 248 patients who underwent exercise testing within 7 days after presentation in the ED. Outcome is the predictive value of exercise testing in terms of major adverse cardiac events (MACE) within 6 weeks after presentation. RESULTS: In low-risk patients (HEART score ≤ 3), 63.1 % were negative tests, 28.6 % non-conclusive and 8.3 % positive; the latter were all false positives. In the intermediate-risk group (HEART score 4-6), 30.9 % were negative tests, 60.3 % non-conclusive and 8.8 % positive, half of these positives were false positives. In the high-risk patients (HEART score ≥ 7), 14.3 % were negative tests, 57.1 % non-conclusive and 28.6 % positive, of which half were false positives. CONCLUSION: In a chest pain population risk stratified with HEART, exercise testing has only a modest contribution to clinical decision making. 50 % of all tests are non-conclusive, with high rates of false positive tests in all three risk groups. In intermediate-risk patients, negative exercise tests may contribute to the exclusion of disease. Clinicians should rather go for sensitive tests, in particular in patients with low HEART scores.

Tricuspid valve regurgitation as a presenting symptom of metastasized carcinoid tumor.

A 66-year-old woman was diagnosed with hepatic metastasized carcinoid tumor of the ileocecal junction resulting in elevated plasma chromogranin A levels and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. Further examination showed right-sided heart failure with severe tricuspid valve regurgitation. Carcinoid tumors produce serotonin which leads to flushing, secretory diarrhea, bronchospasm and hypotension, known as carcinoid syndrome. Serotonin is metabolized to 5-HIAA, which is inactive, in the liver and the lungs. However, hepatic metastases may result in direct exposure of the heart to serotonin, which induces plaque-like deformities on the tricuspid valve, and in turn induces valve regurgitation. This condition is known as carcinoid heart disease. Tricuspid valve regurgitation may induce risk of massive blood loss in case of liver surgery through high-volume backflow in the hepatic veins. This report shows the clinical relevance of carcinoid heart disease in the perioperative setting.