Hypercholesterolemia Treatment Patterns and Lipid Target in ACS Patients: HYDRA-ACS Registry

The multicenter HYDRA-ACS registry provided insights into current treatment situation of hyperlipidemia after acute coronary syndrome (ACS) among patients in Germany. The study findings showed that despite receiving lipid-lowering therapy (LLT), only half of very high-risk patients achieved recommended lipid targets (<70 mg/dL) within 12 months post ACS

Key Takeaway

• The HYDRA-ACS registry investigating the clinical characteristics and current treatment of very high-risk patients with ACS and hyperlipidemia in Germany showed:
  • Two-thirds of the patients received LLT at the time of index event, while all the patients received therapy at 12 months post event
    • Statins were the most commonly prescribed LLT (85.0%), followed by cholesterol resorption inhibitors (32.9%)
    • Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were prescribed to only 0.7% of patients
  • Only half (50%) of the patients achieved recommended target level of <70 mg/dL (2016 ESC/EAS dyslipidemia guideline), despite significant decrease in low-density lipoprotein cholesterol (LDL-C) level at 12-month follow-up
  • Moderate increase in high-density lipoprotein cholesterol (HDL-C) (45 to 47 mg/dL) and decrease in triglycerides (148 to 119 mg/dL) were observed after 12 months
• The study highlighted that an increased adoption of modern treatment approaches, such as PCSK9i, could improve the lipid target achievement in very high-risk patients in the future.

Why This Matters

• Patients with ACS are at high risk of subsequent cardiovascular (CV) events; therefore, long-term treatment of CV risk factors, such as hyperlipidemia, hypertension, or diabetes mellitus, is critical in preventing further progression.
  • However, many patients do not achieve recommended target levels of LDL-C, despite receiving LLT.
• Therefore, HYDRA-ACS registry was initiated to provide insights into the current treatment situation for very high-risk patients with ACS and hyperlipidemia in Germany.

Study Design

• HYDRA-ACS study (national, prospective, multicenter, non-interventional registry) was conducted across 24 centers in Germany.
• Inclusion criteria: Adult ACS patients (≥18 years) with (i) LDL-C >155 mg/dL and first-degree relative with premature myocardial infarction (MI)/premature MI; (ii) LDL-C >190 mg/dL without premature MI/without premature MI in first-degree relative
• Study objectives (baseline to 12-month follow-up): (i) lipid target achievement as measured by LDL-C reduction over time and absolute and relative reductions in LDL-C; (ii) absolute and relative change in total cholesterol, HDL-C, and triglycerides; (iii) use of non-drug LLT (lifestyle and nutrition) and percentage of patients using non-drug LLT over time, as well as use of LLT and percentage of patients receiving LLT over time; (iv) drug utilization patterns for secondary prevention and percentage of patients receiving such pharmacotherapy over time; and (v) CV and cerebrovascular events over time, including percentage of patients with complications at baseline, and percentage of patients with non-fatal events since baseline

Key Results

• A total of 391 ACS patients were enrolled: After exclusion of 38 patients, baseline analysis set (BAS)^* comprised of 353 patients and 140 patients were included in the full analysis set (FAS)^*.

Key baseline characteristics in BAS and FAS group:

BAS, Baseline analysis set; BMI, Body mass index; FAS, Full analysis set; SD, Standard deviation

Cross-sectional analysis (BAS):

• Most common LLT: Statins (40.0%), cholesterol resorption inhibitors (9.4%)
• Lifestyle and nutrition: 46.2% of patients had no physical exercise, while only 15.0% exercised >3 times/week. 73.9% consumed fruits and vegetables at least 3 times/week, while 69.7% ate fish (<2 times/week). 47.9% of patients consumed alcohol (<2 drinks/day) and 45.6% were smokers
• Frequently used CV pharmacotherapies: Antihypertensives (angiotensin-converting enzyme inhibitors [ACEi; 32.9%] and beta-blockers [23.8%]), platelet aggregation inhibitors (37.7%), and antidiabetic agents (10.5%)
• Lipid profile levels:
  • Median LDL-C: 166 mg/dL; most patients (65.2%) had a level of >150 mg/dL, with only 5.1% having a level of <70 mg/dL
  • Median total cholesterol: 235 mg/dL, of which 31.6% had a level >260 mg/dL
  • Median HDL-C: 43 mg/dL; majority of patients (65.2%) had a level of <45 mg/dL (men) or <55 mg/dL (women)
  • Median triglycerides: 162 mg/dL; 45.8% had a level of >172 mg/dL

Longitudinal analysis (FAS):

• Use of LLT (12 months vs baseline):
  • Proportion of patients receiving statins (85.0% vs. 36.5%, P = 0.0002) and cholesterol resorption inhibitors (32.9% vs. 8.6%, P = 0.0003) notably increased
  • Statin use peaked post-index event, but slightly declined by 12 months, while the use of cholesterol resorption inhibitor steadily increased from baseline after index event to 12-month follow-up
  • Only 0.7% of patients were prescribed PCSK9i at 12 months after ACS o Use of combination therapy increased
• Lifestyle and nutrition: Proportion of patients engaging in no physical exercise decreased from 40.0% (baseline) to 24.0% at 12 months (P <0.0001); consumption of fruit and vegetables (P = 0.0222) and fish (P = 0.0162) increased, while alcohol decreased (P = 0.0019)
• CV pharmacotherapies: Increase in the proportion of patients (12 months vs baseline) receiving antihypertensives (mostly beta-blockers [64.3% vs 23.6%], diuretics [58.6% vs 17.9%], angiotensin II receptor blockers [30.0% vs 16.4%], and ACEi [42.1% vs 29.3%], P2Y12 antagonists (35.7% vs 9.3%), and other platelet aggregation inhibitors (77.9% vs 26.4%)
• Lipid profile levels:
  • Median LDL-C: Significantly decreased at 12-month follow-up visit vs baseline, with increase in proportion of patients having levels <70 or <55 mg/dL.
  • A moderate increase in median HDL-C and decrease in median triglyceride level were seen post 12 months

BAS, baseline analysis set; FAS, full analysis set; HDL, high-density lipoprotein; IQR, interquartile range; LDL, low-density lipoprotein

Outcomes assessed in FAS during 12-month follow-up:

• Percutaneous coronary intervention (PCI; 25.9%), cardiac catheterization without PCI (12.9%), and MI (2.4%)
• Stroke and transient ischemic attack (0.0%)
• Overall, 38.8% of patients required hospitalization due to an event and 68.2% of patients received rehabilitation therapy
• No deaths were reported

Key Limitations

• Severe loss to follow-up of patients during the study period
• Differences in patient characteristics between those with and without follow-up, such as higher proportions of male patients, those with diabetes, and coronary heart disease might have impacted the outcomes data, requiring cautious interpretation of rates.

^*BAS included eligible patients with documented entries in the first eCRF section (used for cross-sectional data analysis). FAS comprised all BAS patients with LDL-C and LLT documentation at index event and 12-month follow-up (used for longitudinal data analysis); Note: Conversion factor – to get from mg/dL to mmol/L for total cholesterol, HDL, and LDL: multiply by 0.02586 and for triglycerides: multiply by 0.01129

Please refer source publication Gitt AK, et al for additional details.