PracticeUpdate: Cardiology | Vol1 - No.2 - 2016

CONFERENCE COVERAGE

ESC 2016

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Lipoprotein(a) apheresis proves beneficial in refractory angina Lipoprotein apheresis, a therapy normally used to fil- ter excess cholesterol from the blood of patients with fa- milial hypercholesterolemia, may play a role in patients with refractory angina, reports a prospective, ran- domised, sham-controlled, blinded, crossover study. T ina Khan, MRCP, of Impe- rial College, London, UK, explained that the extracorpor- eal treatment resulted in significant improvement over sham therapy in patients with refractory angina and raised levels of lipoprotein(a). Lipoprotein(a) is similar in structure to low density lipoprotein cholesterol, except for an additional, attached protein-apolipoprotein(a). Raised lipoprotein(a) is a strong risk factor for coronary heart disease and may be prevalent in patients with refractory angina. with cardiac magnetic resonance imaging, was myocardial perfusion reserve, which is the ratio of myocar- dial blood flow at stress vs rest after 3 months of lipoprotein apheresis, compared to baseline.

• Angina frequency score (mean change of 35.0 vs –5.0) • Quality of life score (mean change of 25.8 vs 4.6) In the fifth domain, SeattleAngina Questionnaire treatment satisfac- tion score improved slightly, by 6.25, during apheresis vs 0.0 or no change during sham administration. Simi- larly, physical component scores of quality of life assessed by the Short Form-36 Questionnaire also im- proved significantly after apheresis but not sham administration. Dr Khan concluded, “Our study was the first randomised controlled trial to assess the impact of lipopro- tein apheresis in patients with refrac- tory angina and raised lipoprotein(a), in the absence of significantly raised low density lipoprotein cholesterol. “Findings suggest that lipopro- tein apheresis provides significant clinical benefit to patients with refractory angina in the context of raised lipoprotein(a). The outcome represents a much needed novel treatment option for this therapeu- tically challenging patient cohort.”

A significant increase of 0.63 in myocardial perfusion reserve was observed after apheresis treatment vs sham (P < 0.001). Specifically, myocardial perfusion reserve in- creased from 1.45 to 1.93 with apheresis, and did not change sig- nificantly after sham. Secondary endpoints of carotid wall volume and distensibility also improved after apheresis, as did exercise capacity, symptoms of angina, and quality of life scores. These parameters did not improve after sham. Significant symptom improve- ment was observed after apheresis but not after sham in four of five domains in the SeattleAngina Ques- tionnaire, including: • Physical limitation score (median change of 27.8 vs –4.2) • Angina stability score (mean change of 17.5 vs –3.75)

“Angina refractory to both medical therapy and revascularisation is a de- bilitating condition that is increasing in frequency, and there is a pressing need for novel treatments for these patients. Such patients continue to suffer with troublesome angina despite optimal medical therapy, as well as surgical and/or percutaneous coronary revascularisation. Treat- ment options are limited,” she said. “Our trial provided the first evidence that lipoprotein apheresis leads to improvement among these patients in the primary endpoint of myocardial blood flow, as measured by myocardial perfusion reserve, as well as the secondary endpoints of exercise capacity, angina symptoms, quality of life, and atheroma burden. This treatment approach could im- prove the cardiac health and lives of such patients.”

Studies suggest that elevated lipoprotein(a) may promote ath- erosclerosis and reduce myocardial perfusion, but no effective pharma- cologic treatment is yet approved to treat elevated lipoprotein(a). Elevat- ed lipoprotein(a) is essentially resist- ant to conventional lipid-lowering treatment with statins. Dr Khan and colleagues have now shown that lipoprotein(a) can effectively be lowered with lipoprotein apheresis. The apheresis study included 20 patients with refractory angina and elevated lipoprotein(a) levels above 500 mg/L. Patients were randomised to weekly lipoprotein apheresis or a sham procedure for 3 months, then crossed over for another 3 months, with a 1-month washout period be- tween the two. The primary outcome, measured

Functional imaging for suspected CHD can help avoid angiography Initial investigation of patients with suspected coronary heart disease using functional imaging rather than guideline-directed care resulted in significantly less unnecessary angiography, outcome of the Clinical Evaluation of MAgnetic Resonance imaging in Coronary heart disease 2 (CE-MARC 2) study shows.

J ohn Greenwood, PhD, of the University of Leeds, UK, said that the findings could exert an important impact on referral rates for invasive coronary angiography, and potentially healthcare costs. “Rates of invasive angiography are considered too high among patients with suspected coronary heart disease,” he said. “Our findings show that both cardiovascular magnetic resonance and myocardial perfusion scintigraphy significantly reduced rates of unnecessary angiography compared to guideline-directed care, with no penalty in terms of major adverse cardiovascular events. This suggests that functional imaging should be adopted on a wider basis, even in high-risk patient subgroups.” CE-MARC 2 included 1202 patients with suspected coronary heart disease from six UK centres. Patients were randomised to functional imaging-based investigation with

coronary angiography, with secondary endpoints of major ad- verse cardiovascular events, and positive angiography within this same time period. Twenty-two percent of the study population underwent coronary angiography within 12 months, with unnecessary angiography performed in 28.8% of the NICE guidelines group, 7.5% of the cardiovascular magnetic resonance group, and 7.1% of the myocardial perfusion scintigraphy group. The adjusted odds ratio of unnecessary angiography for the cardiovascular magnetic resonance group vs the NICE guide- lines group was 0.21 (95% confidence interval 0.12–0.34; P < 0.001), with no statistically significant difference between the cardiovascular magnetic resonance and myocardial perfusion scintigraphy groups. Among the three strategies, there was no difference in short- term major adverse cardiovascular events or posi- tive angiography rates.

either cardiovascular magnetic resonance (n=481), myocardial perfusion scintigraphy (n=481), or guideline-directed inves- tigation (n=240) based on National Institute for Health and Care Excellence (NICE) guidelines. In the latter group, those with a pre-test likelihood of 10–29% (low risk for coronary heart disease based on age, gender, symptom characteristics, and clinical history) were scheduled for cardiac computed tomography. Those with a pre-test likelihood of 30% to 60% (intermediate risk) were scheduled for myocardial perfusion scintigraphy, and those with a high pre-test likelihood were sent directly to coronary angiography. The primary endpoint was unnecessary coronary angiogra- phy within 12 months, defined by the absence of significant stenosis as measured by fractional flow reserve or quantitative

Dr Greenwood noted, “Worldwide, myocardial perfusion scintigraphy is the most commonly used test to assess suspected coronary heart disease, but cardiovascular magnetic resonance is increasingly recognised as conferring high di- agnostic accuracy and prognostic value. Though the results of CE-MARC 2 showed no difference between the cardiovascular magnetic resonance and myocardial perfusion scintigraphy strate- gies in terms of unnecessary angiography rates, our original, 2012 CE-MARC study showed that cardiovascular magnetic resonance yielded higher diagnostic accuracy than myocardial per- fusion scintigraphy, and, as published in 2016, as a stronger predictor of risk of major adverse cardiovascular events.” Dr Greenwood concluded, “These results show that broader use of functional imaging (cardiovas- cular magnetic resonance or myocardial perfusion scintigraphy), in low-, intermediate-, and high-risk patient groups, could reduce rates of invasive angiography that ultimately shows no obstructive coronary disease. In addition, CE-MARC and CE- MARC 2 further support cardiovascular magnetic resonance as an alternative to myocardial perfusion scintigraphy for the diagnosis and management of patients with suspected coronary heart disease.”

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