{"id":333668,"date":"2020-08-04T11:20:27","date_gmt":"2020-08-04T09:20:27","guid":{"rendered":"https:\/\/medizinonline.com\/new-agla-pocket-guide-prevention-of-atherosclerosis\/"},"modified":"2020-08-04T11:20:27","modified_gmt":"2020-08-04T09:20:27","slug":"new-agla-pocket-guide-prevention-of-atherosclerosis","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/new-agla-pocket-guide-prevention-of-atherosclerosis\/","title":{"rendered":"New AGLA Pocket Guide “Prevention of Atherosclerosis"},"content":{"rendered":"

To reduce the risk of cardiovascular disease, low LDL-C levels are critical [1]. This finding is also reflected in the ESC\/EAS Dyslipidemia Guidelines – the basis for the new Swiss AGLA pocket guide [2,3]. Lowering LDL-C as much as possible, which is recommended here, and strict risk assessment bring escalation therapies, such as PCSK9 inhibitors, into the focus of cardiovascular prevention [2\u20134].<\/strong><\/p>\n

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With more than 21,000 deaths per year, cardiovascular diseases are the most common cause of death in Switzerland [5]. For the prevention of cardiovascular disease, it is crucial to identify the underlying causes and counteract them at an early stage. Here, the focus is particularly on LDL-C (low-density lipoprotein cholesterol), which, according to meta-analyses of genetic studies, prospective epidemiological studies, Mendelian randomization trials, and randomized clinical trials, contributes directly to the development of atherosclerotic cardiovascular disease (ASCVD) [2,6].<\/p>\n

“The lower, the better”<\/strong><\/p>\n

Low LDL-C levels are inversely associated with a lower incidence of ASCVD events [1,7]. On the one hand, this applies to individuals who genetically have very low LDL-C levels, but on the other hand, it also applies to a drug-induced absolute reduction in LDL-C [1,7]. Thus, the annual rate of myocardial infarction, coronary revascularization, and ischemic stroke can be reduced by one-fifth by lowering LDL-C by 1 mmol\/l. Lowering LDL-C by 2 to 3 mmol\/l is even thought to reduce the risk of these serious cardiovascular events by 40 to 50 percent [1]. In addition, LDL-C levels below the previously recommended target levels are associated with additional clinical benefits, but not with additional safety concerns [8].<\/p>\n

Focus on low LDL-C target levels and cardiovascular risk.<\/strong><\/p>\n

Accordingly, the new pocket guide of the Lipids and Atherosclerosis Working Group (AGLA) of the Swiss Society of Cardiology (SGK) for the prevention of atherosclerosis, which is based on the current  guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), recommends strict LDL-C target values. These  are lower the higher a patient’s risk rating (Table 1)<\/strong> [3].<\/p>\n

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AGLA Risk Calculator<\/strong><\/p>\n

To estimate overall cardiovascular risk, the AGLA Risk Calculator<\/a> is available online, which calculates the risk of having a fatal coronary event or nonfatal myocardial infarction within 10 years. This includes family history, HDL-C (high-density lipoprotein cholesterol) and triglycerides as risk factors and is thus more specific than the ESC-SCORE, which can also be used for risk assessment [2, 3, 9].<\/p>\n\n\n\n
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\"\"The new AGLA pocket guide for the prevention of atherosclerosis<\/strong><\/span><\/div>\n
Focus on dyslipidemia <\/strong><\/em><\/span><\/div>\n
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The 7th edition of the popular AGLA pocket guide “Prevention of Atherosclerosis” has recently become available. The recommendations on cardiovascular risk prevention and adequate treatment options adapted for Switzerland are based, among others, on the ESC\/EAS guidelines updated in 2019.<\/p>\n

The new AGLA pocket guide is available at www.agla.ch<\/a>.<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Treatment algorithm for hypercholesterolemia<\/strong><\/p>\n

Based on the individually determined overall cardiovascular risk, the AGLA pocket guide recommends the following treatment algorithm in the presence of hypercholesterolemia, following the ESC\/EAS guidelines (Figure 1)<\/strong> [2, 3]. In the presence of marked hypercholesterolemia, it is also important to start lipid-lowering treatment early, as ASCVD risk is determined by both LDL-C concentration and exposure duration [9].<\/p>\n

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Increasing importance of PCSK9 inhibitors<\/strong><\/p>\n

[2,3]The lower LDL-C target values compared with previous recommendations and the more stringent calculation of cardiovascular risk mean that more patients may now benefit from escalation therapy with PCSK9 inhibitors . In primary prevention, this mainly affects patients with severe heterozygous familial hypercholesterolemia (FH) and an LDL-C >5.0 mmol\/l or >4.5 mmol\/l if another risk factor is present, and in secondary prevention, patients with manifest ASCVD and an LDL-C >2.6 mmol\/l (see also box “BAG limitations for the use of evolocumab”) [3]. Thus, the current recommendations mark an advance in cardiovascular risk prevention, especially for patients at high and very high risk. This is because PCSK9 inhibitors can effectively reduce LDL-C levels – in the case of evolocumab (Repatha\u00ae<\/sup>) – by about 60 percent [4]. In this regard, evolocumab has one of the largest clinical efficacy and safety study programs among the available PCSK9 inhibitors with more than 41,000 patients [10].<\/p>\n

Evolocumab lowers LDL-C levels and thus cardiovascular risk<\/strong><\/p>\n

The FOURIER Outcome Study showed that evolocumab plus statin therapy reduced cardiovascular risk (composite endpoint of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) by 15 percent in patients with ASCVD and LDL-C levels \u22651.8 mmol\/l compared with placebo (HR 0.85; 95% CI: 0.79-0.92; p<0,001) [4]. A secondary analysis of the FOURIER trial also found a significant linear relationship between LDL-C reduction and cardiovascular risk with evolocumab, underscoring the importance of LDL-C lowering in cardiovascular prevention [8]. That it is important, as recommended in the AGLA and ESC\/EAS guidelines, to aim for a drastic reduction in LDL-C levels through escalation therapies, especially in high-risk patients, is supported by a further secondary analysis of the FOURIER study, in which the absolute risk reduction was particularly large in patients with a recent myocardial infarction [11]. Overall, evolocumab showed very good tolerability in various studies, comparable to the control groups. Even at low LDL-C levels, no safety signals or abnormalities in neurocognitive events were detected, and treatment with evolocumab for five years resulted in stable LDL-C lowering with a consistent safety profile [8,12,13].<\/p>\n\n\n\n
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Indication of Repatha\u00ae<\/sup> (Evolocumab)<\/strong><\/div>\n
Repatha\u00ae <\/sup>(evolocumab) is approved concomitantly with diet and in addition to a maximum tolerated statin dose with or without other lipid-lowering therapies for the treatment of adults with hypercholesterolemia (including heterozygous FH) or adults and adolescents 12 years of age and older with homozygous FH who require additional LDL-C lowering. In addition, Repatha\u00ae<\/sup> is indicated to reduce the risk of cardiovascular events (myocardial infarction, stroke, and coronary revascularization) in patients at high cardiovascular risk [14].<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Conclusion<\/strong><\/p>\n

LDL-C is one of the main causes of ASCVD. This has been proven many times and is increasingly establishing itself as a dogma in the prevention of cardiovascular disease [2,6]. The current ESC\/EAS guidelines respond to this and further emphasize the principle of “the lower, the better” by lowering the LDL-C target values, tightening the risk categories, and making corresponding adjustments to the recommended treatment algorithm, which is also reflected in the new AGLA pocket guide  [2,3,9]. As a result, PCSK9 inhibitors are becoming increasingly important as adjunctive therapy to intensive statin therapy [2]. Thus, evolocumab may further lower LDL-C, thereby reducing cardiovascular risk, without being associated with safety implications [4,8,12,13].<\/p>\n\n\n\n
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BAG limitations for the use of Evolocumab [15]<\/strong><\/div>\n
In Switzerland, the cost of therapy with evolocumab concomitant with diet and in addition to a maximum tolerated dose of intensified LDL-C-lowering therapy is covered by health insurance only if<\/div>\n
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