MANNHEIM, Germany — When it comes to lowering cholesterol, there is still a lot of room for improvement for patients with cardiovascular diseases, according to researchers. The results of the DA-VINCI study showed a massive discrepancy between the target levels of LDL cholesterol stipulated in the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines and the levels achieved in clinical practice. The results of the recent SANTORINI study once again highlight the need for the intensive application of lipid-lowering drugs.
In the SANTORINI study, 9606 high-risk or very-high-risk patients were recruited. “Broadly speaking, the target values of 70 mg/dL for high-risk patients and 55 mg/dL for very-high-risk patients were not achieved,” said Roland Klingenberg, MD, consultant cardiologist at Kerckhoff Heart and Thorax Center in Bad Nauheim, Germany, at a symposium during the Annual Meeting of the German Society for Cardiology.
In Klingenberg’s opinion, the risk is often underestimated for patients with cardiovascular issues. In everyday practice, these patients have “much higher LDL cholesterol levels than recommended in the guidelines,” he said. Even in the DA-VINCI study, only 54% of patients achieved the target LDL cholesterol levels stipulated in the 2016 guidelines, and only 33% of patients achieved the much stricter target values in the 2019 guidelines.
“We have the resources to achieve more of a reduction in LDL cholesterol — the therapy for this continues to grow more intense and sophisticated — but in reality, implementation is often very different,” said Klingenberg. Moderate-intensity monotherapy with a statin continues to be the most common lipid-lowering therapy in Europe. Only a minority of patients receive combination therapy, and PCSK9 inhibitors are rarely prescribed. The reasons behind this gulf are “definitely also economically grounded.”
Good tools are available, but the drug guidelines stipulate that before using a PCSK9 inhibitor, a whole array of other substances must first be used. The following treatment algorithm is in place:
Statin (high strength and at a high dose)
Statin + ezetimibe
Statin + ezetimibe + bempedoic acid
Statin + ezetimibe + bempedoic acid + PCSK9 inhibitor
Apheresis + statin + ezetimibe +/- bempedoic acid +/- PCSK9 inhibitor.
Should a change in lifestyle be insufficient, statin therapy is initiated. If the target value cannot be achieved through this therapy, a combination of ezetimibe with, if necessary, bempedoic acid follows. If even this is not enough, a PCSK9 inhibitor can then be added.
Nevertheless, Germany underperforms in the achievement of target LDL-C values, said Oliver Weingärtner, MD, senior physician of interventional cardiology at the Jena University Hospital in Jena, Germany. Less than 20% of very-high-risk patients in Europe achieve the target LDL-C values recommended in the ESC/EAS guidelines.
Strike Early, Strike Hard
Weingärtner and colleagues took the unsatisfactory situation as an opportunity to start the prospective cohort study “Jena auf Ziel – JaZ” (“Jena on target”). An early combination therapy of atorvastatin (80 mg) and ezetimibe (10 mg) was initiated upon hospitalization in 85 patients with ST-segment elevation myocardial infarction (STEMI). During the follow-up period, the lipid-lowering therapy was escalated with bempedoic acid and PCSK9 inhibitors so that every patient achieved the recommended target LDL cholesterol levels.
On discharge from hospital, 32.9% of the subjects had achieved the target LDL cholesterol values on atorvastatin and ezetimibe. After 4-6 weeks, 80% of all patients who had been treated with atorvastatin and ezetimibe at the time of the infarct achieved the ESC/EAS target LDL cholesterol values.
The combined lipid-lowering therapy was escalated with either bempedoic acid or PCSK9 inhibitors in 20 patients. Every patient achieved an LDL cholesterol value of 55 mg/dL or less under the triple lipid-lowering therapy. The combined lipid-lowering therapy was well tolerated and had only a few side effects.
“Through early combination therapy with a high-dose statin and ezetimibe, and an escalation of the lipid-lowering therapy with either bempedoic acid or PCSK9 inhibitors, potentially all STEMI patients can achieve the target LDL cholesterol levels recommended by the ESC/EAS without any significant side effects,” said Weingärtner.
Since 2020, some 20 cities and regions have held launch events based on the JaZ “auf Ziel” model. In some places, two networking events have also taken place.
Elisabeth Steinhagen-Thiessen, MD, set up an outpatient lipid clinic at the Center for Internal Medicine of the Rostock University Medical Center in Germany. She said that PCSK9 inhibitors can be economic, prescribable, and remunerable for the following populations:
Patients with heterozygous familial or nonfamilial hypercholesterolemia or mixed dyslipidemia
Patients with verified vascular disease and regular additional risk factors
Therapy-refractory patients with documented maximum nutritional and medicinal lipid-lowering therapy over 12 months
Patients who were unable to reduce their LDL cholesterol values sufficiently and for whom an indication for LDL apheresis is assumed.
Because of limited financial resources, Steinhagen-Thiessen emphasized that the focus must be “on education and prevention” and that “the therapeutic focus [should be] on the at-risk patients.” The government must initiate social discourse in this regard, instead of avoiding it as they have done in the past.
Good Documentation Essential
Bernd Nowak, MD, of the CardioVascular Center Bethanien in Frankfurt, made it clear that the patients are owed individual, adequate therapy. According to Nowak, lipid treatment is caught between two opposing poles: the one according to paragraph 2 of the German Social Code, Book V (SGB V), which defines the services, and the other according to paragraph 12 of the SGB V on economic viability.
Section 2 of the SGB V dictates that the quality and efficacy of the services must align with the recognized level of medical knowledge and take into account medical progress. However, according to the principle of economic viability, the services must be adequate, appropriate, and economic, and they may not exceed what is necessary.
Adequate therapy refers to that which is in line with guidelines, studies, and standards, said Nowak. However, depending on the substance, the daily treatment costs for lipid lowering can vary significantly. The daily cost for rosuvastatin + ezetimibe is EUR 0.34, for bempedoic acid + ezetimibe it is EUR 2.60 (US $2.85), and for the PCSK9 inhibitor evolocumab it is as high as EUR 29.52 (US $32.40). “But you cannot then say, ‘That is too expensive, therefore I won’t treat my patient.’ We have to administer treatment in line with the medical standard,” said Nowak, referring to section 630a para. 2 of the German Civil Code.
A ruling by the State Court of Hamburg (ref. 336 0 76/17) dated May 19, 2021, demonstrates that malpractice shall not exist if therapy has been administered in line with the guidelines and in accordance with the target LDL cholesterol values. “Earlier intervention would have been suitable for the claimant not to suffer any injury to health, or only to a lesser extent,” said the ruling.
Even if the fear of recourse continues to resonate, some of this has been quelled in recent times. Nowak recalled the following considerations:
In the first 2 years after certification (the honeymoon period), there can be no recourse claims.
Principle: Consultation before recourse.
Consultation before recourse renews after 5 years according to the “amnesty regulation.”
Special features of the practice for medical reasons (for sick patients in particular, it is important to document properly).
A maximum 5% of a department’s physicians are audited.
Obligation to state reasons for all audit requests.
Retroactive shortening of audit periods to 2 years.
Applications must be submitted 6 months before the period ends.
Nowak also recalled that recourse claims are relatively rare. In February 2016, the Association of German Cardiologists surveyed certified cardiologists to see whether they had experienced any recourse claims in the past 5 years due to lipid-lowering therapy. Approximately 92% of those surveyed indicated that they had not experienced any recourse claims, and 7.9% of those surveyed indicated that they had.
In terms of the drugs that led to the recourse, PCSK9 inhibitors were the leader (58.8% of cases). “Good and detailed documentation is crucial. If I have to undergo an audit and I can easily prove why I administered treatment in such a way, said audit will usually go well for me. It can become difficult if I don’t document everything properly,” said Nowak.
This article was translated from the Medscape German Edition.
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