Clinical impact of more than 50% reduction in low-density lipoprotein cholesterol at 6 weeks after percutaneous coronary intervention for acute coronary syndrome
K Murai, K Mitsui, T Iwai, K Sawada, H Matama, S Honda, M Fujino, S Yoneda, K Nakao, K Takagi, Y Kataoka, Y Asaumi, T NoguchiAbstract
Background
Early intensive lipid-lowering therapy is recommended after acute coronary syndrome (ACS), and current guidelines recommend assessing attainment of lipid-lowering targets within 4–6 weeks; however, the prognostic significance of achieving a more than 50% reduction in low-density lipoprotein cholesterol (LDL-C) shortly after percutaneous coronary intervention (PCI) remains unclear.
Purpose
To elucidate the prognostic value of achieving a more than 50% reduction in LDL-C at 6 weeks after PCI in ACS.
Methods
This retrospective study analyzed 1,505 consecutive patients with ACS who underwent PCI. LDL-C levels at 6 weeks and 1 year were estimated by linear interpolation using all available post-procedural measurements to calculate values at 42 and 365 days after PCI, respectively (Figure 1). The primary clinical outcome was major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or stroke.
Results
The mean age was 71.0 years, and 74.1% were men. ST-elevation myocardial infarction accounted for 49.3% of cases, and a total of 32.0% had a history of prior cardiovascular events. The mean baseline LDL-C level was 2.95 ± 1.02 mmol/L. At 6 weeks, 574 patients (38.1%) achieved an LDL-C reduction greater than 50%. Over a median follow-up of 944 days (interquartile range: 554–1,430 days), the 6-year incidence of MACE was significantly lower in patients who achieved an LDL-C reduction greater than 50% at 6 weeks compared with those who did not (11.5% vs. 21.7%; adjusted hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.48–0.99; P=0.047) (Figure 2). Each 10% greater LDL-C reduction at 6 weeks from baseline was independently associated with lower MACE risk (adjusted HR, 0.92; P=0.003), whereas absolute LDL-C level at 6 weeks (per 1 mmol/L increase) and attainment of LDL-C <1.4 mmol/L at 6 weeks were not (adjusted HR, 1.26; P=0.140 and adjusted HR, 0.84; P=0.298, respectively) (Figure 3). Of note, restricted cubic spline analysis demonstrated a monotonic inverse association between LDL-C reduction at 6 weeks and MACE risk, with no significant nonlinearity (P for nonlinearity = 0.37) (Figure 4). Interestingly, a shorter time to achieving an LDL-C reduction greater than 50% was significantly associated with a lower risk of MACE (per 10-day delay: adjusted HR, 1.01; 95% CI, 1.00–1.01; P=0.045). Furthermore, compared with patients who did not achieve an LDL-C reduction greater than 50% within 1 year, those who achieved this reduction within 6 weeks had a significantly lower risk of MACE (adjusted HR, 0.69; 95% CI, 0.45–0.99; P=0.048), whereas those achieving it between 6 weeks and 1 year did not (P=0.089).
Conclusions
Achievement of an LDL-C reduction of more than 50% at 6 weeks after PCI was associated with a lower long-term risk of MACE in patients with ACS. These findings support current guideline recommendations emphasizing an early and intensive lipid-lowering strategy.