Core messages
In patients with chronic coronary artery disease and elevated lipid levels, statin therapy according to the «treat-to-target» strategy is as effective as a fixed-dose strategy of high-dose statins. This is the result of a large randomized study from South Korea, which has been published in the journal JAMA ( ).The two strategies are still controversially discussed by German professional societies.
Background
Chronic coronary heart disease (chronic CHD) is high on the cause of death statistics of Western countries, including Germany, as is acute myocardial and cerebral infarction. Hypercholesterolemia is a major risk factor for this. By lowering cholesterol with HMG-CoA reductase inhibitors, the statins, the risks and mortality of any cause are reduced. According to the recommendations of international, but also German professional societies, there are two strategies for lipid lowering in chronic CHD:
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The fixed dose strategy, according to which all patients with CHD should be recommended a fixed high-dose statin therapy if there are no contraindications (further lipid determinations or adjustments are omitted), and which
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Target strategy, according to which LDL cholesterol levels in patients with chronic CHD reach a target value <70 mg/dl (<1,8 mmol/l) or reduced by at least 50 % if the baseline value is between 70 and 135 mg/dl (1,8 and 3,5 mmol/l) (1).
The fixed dose strategy, according to which all patients with CHD should be recommended a fixed high-dose statin therapy if there are no contraindications (further lipid determinations or adjustments are omitted), and which
Target strategy, according to which LDL cholesterol levels in patients with chronic CHD reach a target value <70 mg/dl (<1,8 mmol/l) or reduced by at least 50 % if the baseline value is between 70 and 135 mg/dl (1,8 and 3,5 mmol/l) (1).
South Korean researchers directly compared these two strategies in a large, prospectively randomized open-label trial (2).
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Design
Type of study: prospective randomized, multicenter, open clinical trial with the hypothesis that the target strategy is not inferior to the fixed high-dose strategy (non-inferiority study) -
Participants: CHD, symptomatic in 81%, 56% percutaneous coronary intervention in history, 73% men, average age of the entire group: 65.1 years, average body mass index: 24.7, kg/m2, 67% with hypertension, 33% with diabetes mellitus, total cholesterol: average 156.5 mg/dl, LDL cholesterol: average 86.5 mg/dl
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Randomization: 4400 subjects (3172 men) in a ratio of 1 : 1 in a group with
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target strategy (titration of the statin until an LDL value between 50-70 mg/dl is reached) or in the group with
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high fixed statin dose (20 mg rosuvastatin or 40 mg atorvastatin daily)
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Primary endpoint: death, myocardial infarction, stroke or percutaneous coronary revascularization at 3 years (non-inferiority: difference ≤ 3 percentage points)
Design
Type of study: prospective randomized, multicenter, open clinical trial with the hypothesis that the target strategy is not inferior to the fixed high-dose strategy (non-inferiority study)
Participants: CHD, symptomatic in 81%, 56% percutaneous coronary intervention in history, 73% men, average age of the entire group: 65.1 years, average body mass index: 24.7, kg/m2, 67% with hypertension, 33% with diabetes mellitus, total cholesterol: average 156.5 mg/dl, LDL cholesterol: average 86.5 mg/dl
Randomization: 4400 subjects (3172 men) in a ratio of 1 : 1 in a group with
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target strategy (titration of the statin until an LDL value between 50-70 mg/dl is reached) or in the group with
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high fixed statin dose (20 mg rosuvastatin or 40 mg atorvastatin daily)
target strategy (titration of the statin until an LDL value between 50-70 mg/dl is reached) or in the group with
high fixed statin dose (20 mg rosuvastatin or 40 mg atorvastatin daily)
Primary endpoint: death, myocardial infarction, stroke or percutaneous coronary revascularization at 3 years (non-inferiority: difference ≤ 3 percentage points)
Main results
In the two study arms, 2200 subjects each randomized.
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After 3 years, 8.1% of patients with the treat-to-target strategy and 8.7% with the «fixed high dose» strategy met the primary endpoint.
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Mortality from any cause was 2.5% in each group.
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There were also no significant differences in the other components of the endpoint, each below the 3% limit.
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The target value of LDL-C of <70 mg/dl had reached after 3 months more patients under fixed high dose than with the target value strategy.However, this did not have a negative impact on the endpoints.
After 3 years, 8.1% of patients with the treat-to-target strategy and 8.7% with the «fixed high dose» strategy met the primary endpoint.
Mortality from any cause was 2.5% in each group.
There were also no significant differences in the other components of the endpoint, each below the 3% limit.
The target value of LDL-C of <70 mg/dl had reached after 3 months more patients under fixed high dose than with the target value strategy.However, this did not have a negative impact on the endpoints.
Clinical significance
According to the authors, the results of the LODESTAR study favor the target strategy of lipid lowering with statins over the strategy of the fixed dose in CHD.
The advantages are savings in the cumulative amount of drugs, because not all patients need a high dose of statins in the long run. Overall, these are well tolerated. Potential adverse effects, however, are statin-associated muscle pain, the development of type 2 diabetes and hepato- and nephrotoxicities.
Regular monitoring of lipids, as required by the treat-to-target strategy, probably also increases adherence. The target strategy is also supported by data from two previous major studies (3, 4).
The target value strategy is recommended by the German Society for Internal Medicine, for example, but also by the DGK, the fixed dose strategy by DEGAM (1).
Funding: public funds
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Source — https://www.univadis.de/viewarticle/koronare-herzkrankheit-zielwertstrategie-der-lipidsenkung-2023a10005pk