Prof. Lale Tokgozoglu reported that this session went into more detail of the guidelines, since the actual presentation of the guidelines had a specific dedicated session. Four main questions were debated here, namely: firstly, should we go for LDL or non HDL? Second, what about upcoming therapies not clarified in the guidelines, focusing particularly on the forthcoming consensus paper of the EAS and ESC to be published soon in the EHJ on PCSK9 inhibitors; thirdly, should we have goals or just aim for a percentage reduction, and lastly, the importance of familial hypercholesterolaemia (FH), as highlighted in the guidelines.
Prof. Tokgozoglu herself addressed the question of which better predicts risk, LDL, non-HDL, or apoB. She mentioned that there is overwhelming evidence of causality of LDL and many randomized trials showing that lowering the LDL decreases risk. So obviously, that is going to be our primary target. However, non-HDL also includes the cholesterol in the very low density lipoprotein, and there is some evidence that non HDL may be a better predictor of risk. So when LDL and non HDL are concordant, they are just as good as each other in predictive terms. Conversely, in insulin resistant states, or in patients with HIV infection, non HDL and LDL may not be concordant, and non HDL may predict risk better in those patients. However, Prof. Tokgozoglu underlines that results of epidemiological studies are conflicting. A study from the Emerging Risk Factors Collaboration suggested that non HDL is not superior. So the take home message here is that LDL should definitely be the primary target, as underlined in the new European guidelines, while non HDL is a secondary target in moderate, high and very high risk patients, once you've achieved your LDL goal.
Next, Olov Wiklund (Goteborg, Sweden) spoke about emerging therapies that are not covered by the guidelines. Indeed, the absence of sufficient evidence for guidelines, the EAS and ESC came together to write a consensus paper examining the conditions where these new therapies could be used. This expert consensus is due to appear soon in the EHJ. There, specific situations where PCSK9 inhibitors could be used are defined. Although there are a lot of unanswered questions regarding PCSK9 inhibitors, and we don't have any outcome data yet, they may be considered in certain situations of very high risk, FH or statin intolerance. There’s also new evidence about lowering LP(a) and apoC3.
The third presentation was by Prof. Guy De Backer, of Ghent, Belgium. He mentioned that the 2013 American guidelines cast doubt on specific goals, and recommended a percent reduction of LDL cholesterol. This has created confusion in the minds of many physicians. Looking carefully, the main message of both sets of guidelines is actually quite similar. We in Europe believe that we should have specific goals, because both the patient and the physician need goals, and patients also adhere better when there is a set goal. So, having an objective is useful. The European guidelines therefore recommend goals, but there is also a percent reduction recommendation. Basically, the patient must get to a goal of <0.70 mg/dL if at very high risk, but if the patient is at very high risk and has a starting LDL level between 70 and 135 mg/dL, you should also aim to achieve a 50% reduction. We are against the fire and forget approach, whereby you give the patient the percentage you think they will achieve, and then forget about. The problem with that strategy is that not everyone responds the same to treatment, and secondly, if the patient doesn’t have a goal to aim for, they’re more likely to discontinue therapy. Indeed, non-adherence is a hot topic, because studies are showing that after discharge for CAD, at 6 months or one year, the medication adherence decreases. However, the wonderful risk reductions achieved in randomized trials can only be replicated if the ordinary patient complies as well as those included in RCTs. It has been shown that cardiovascular events are significantly more frequent when the patient has low compliance, slightly less frequent with moderate adherence, and achieve the lowest frequency with high adherence.
The fourth and final speaker, Dr. Ulrich Laufs (Homburg, Germany) highlighted the importance of FH, which is much more prevalent than previously thought. The classical textbooks say that FH is quite rare, but evidence from Dutch studies indicates that its prevalence may be at least 1 in 200, although rates differ between countries. FH is more risky than just having high cholesterol, so any clinician or cardiologist should look for signs of FH in any patient they see. It is perceived that the diagnosis of FH requires a difficult genetic test, but there are now clinical criteria for the diagnosis for which you don't need sophisticated genetic testing. The guidelines highlight the importance of FH and reviewed the list of clinical criteria for diagnosis, including for example, simple questions regarding family history of early CAD, presence of xanthomas, very high LDL or high under treatment LDL etc. These criteria then yield an overall score for a classification of the risk of FH into definite, probable, or possible.
In conclusion, there are three main take home messages from this session. Firstly, if you want to decrease your patient's cardiovascular risk, then you need to get the patient to goal and make sure they stay there. Second, FH is much more prevalent than previously thought, so every clinician should be on the lookout for it in their patients with CAD. Thirdly, emerging therapies may help the patient get to goal.