ISCHEMIA Trial: Key Questions and Answers

A healthy lifestyle, myocardial revascularisation and medical therapy constitute the three pillars for the treatment of ischaemic heart disease. Lifestyle and optimal medical therapy should be used in all cases. However, the selection of cases for revascularisation among stable patients remains controversial. The ISCHEMIA trial compared an early invasive strategy with revascularisation plus optimal medical therapy against initial optimal medical therapy alone with revascularisation reserved for cases in which symptom control was insufficient. The study included over 5,000 patients with stable coronary artery disease and moderate to severe myocardial ischaemia. No differences were found in relevant clinical outcomes, including all-cause mortality, cardiovascular death, MI, heart failure and stroke, over a follow-up of 3.2 years. Conversely, angina control was better in patients with severe symptomatic angina. Following the tradition of all trials comparing medical therapy alone with revascularisation, the ISCHEMIA trial results are controversial, but an analysis of the design and results of the trial offers important information to better understand, evaluate and treat the growing number of patients with stable chronic ischaemic heart disease and moderate to severe myocardial ischaemia

Reduction in Recurrent Cardiovascular Events with Prasugrel Compared with Clopidogrel in Patients with Acute Coronary Syndromes from the TRITON-TIMI 38 Trial

Aims: In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary endpoint (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel. Methods and results: Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event. Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46–0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25–0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71–0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug). Conclusion: While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with ACS

Safety and efficacy of alirocumab in a real-life setting: the ODYSSEY APPRISE study.

Abstract Aims To obtain safety and efficacy data of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting in high cardiovascular (CV) risk patients with heterozygous familial hypercholesterolaemia (HeFH) or very-high low-density lipoprotein cholesterol (LDL-C) levels despite maximally tolerated dose of statin ± other lipid-lowering therapies (MTD ± LLTs). ODYSSEY APPRISE was a prospective, single-arm, Phase 3b open-label (≥12 weeks to ≤ 30 months) European/Canadian study with alirocumab. Methods and results Patients received alirocumab 75 or 150 mg every 2 weeks, with dose adjustment based on physician's judgment. In total, 994 patients were enrolled and treated. The mean [standard deviation (SD)] duration of alirocumab exposure was 72.4 (42.5) weeks. Patients with HeFH were younger [mean (SD) age of 53.8 (11.6) vs. 61.6 (10.1) years], more likely to be female (41.7% vs. 29.1%) and had higher baseline LDL-C compared with non-familial hypercholesterolaemia (non-FH) patients [mean (SD) of 5.1 (1.7) vs. 4.1 (1.1) mmol/L]. The overall incidence of treatment-emergent adverse events (TEAEs) was 71.6%; common TEAEs included nasopharyngitis (7.8%), myalgia (7.1%), and headache (6.2%). At Week 12, mean (SD) LDL-C was reduced by 54.8 (20.1)% from baseline [2.6 (1.2) mmol/L], maintained for the trial duration. LDL-C was reduced below 1.8 mmol/L and/or by ≥50% reduction from baseline in 69.1% of patients overall, and for 64.7 and 77.4% of the HeFH and non-FH subgroups, respectively. Conclusion In a real-life setting in patients with hypercholesterolaemia and high CV risk, alirocumab was generally well tolerated and resulted in clinically significant LDL-C reductions

Contemporary management of octogenarians hospitalized for heart failure in Europe: Euro Heart Failure Survey II

Aims International guidelines are frequently not implemented in the elderly population with heart failure (HF). This study determined the management of octogenarians with HF enrolled in Euro Heart Failure Survey II (EHFS II) (2004-05). Methods and results We compared the clinical profile, 12 month outcomes, and management modalities between 741 octogenarians (median age 83.7 years) and 2836 younger patients (median age 68.4 years) hospitalized for acute/decompensated HF. Management modalities were also compared with those observed in EHFS I (2000-01). Female gender, new onset HF (de novo), hypertension, atrial fibrillation, co-morbidities, disabilities, and low quality of life were more common in the elderly (all P < 0.001). Mortality rates during hospital stay and during 12 months after discharge were increased in octogenarians (10.7 vs. 5.6% and 28.4 vs. 18.5%, P < 0.001). Underuse and underdosage of medications recommended for HF were observed in the elderly. However, a significant improvement was observed when compared with EHFS I both in the overall HF octogenarian population and in the subgroup with ejection fraction ≤45% for prescription rates of ACE-I/ARBs, beta-blockers, and aldosterone antagonists at discharge (82 vs. 71%; 56 vs. 29%; 54 vs. 18.5%, respectively, all P < 0.01), as well as for recommended combinations and dosage. Prescription rates remained stable for 12 months after discharge in survivors. Conclusion Our study confirms that the contemporary management of very elderly patients with HF remains suboptimal but that the situation is improvin

Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome The IMPROVE-IT Trial

AbstractBackgroundIntensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin.ObjectivesThis analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy.MethodsAll PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis.ResultsAmong 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005).ConclusionsLipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878

Recomendações sobre revascularização do miocárdio

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ESC core curriculum for the general cardiologist (2013)

[No abstract available

Natural History of Patients with Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study

Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in ISCHEMIA trial screen failures with INOCA) was an international cohort study conducted from 2014-2019 involving angina assessments (Seattle Angina Questionnaire [SAQ]) and stress echocardiograms 1-year apart. This was an ancillary study that included patients with history of angina who were not randomized in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease (CAD) status and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between changes in SAQ Angina Frequency score and change in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and compared CIAO participants with ISCHEMIA participants with obstructive CAD who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 vs. 26% of 865 ISCHEMIA participants with obstructive CAD, p\u3c0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [IQR 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (p=0.46) or ISCHEMIA stress echocardiography participants (p=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over one year was not significantly correlated with change in angina (rho=0.029). Conclusions: Improvement in ischemia and improvement in angina were common in INOCA, but not correlated. Our INOCA cohort had a similar degree of inducible wall motion abnormalities to concurrently enrolled ISCHEMIA participants with obstructive CAD. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina