Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators\' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in an important subset of ACS patients, those with non-ST elevation myocardial infarction (NSTEMI) by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.
Lipoprotein(a), or Lp(a), levels and the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on Lp(a) during the peri-infarction and early postinfarction period are not well characterized. This study aimed to describe the trajectory of Lp(a), as well as the effect of PCSK9 inhibition on that trajectory during the peri-infarction and early postinfarction period. Lp(a) levels were obtained within 24 hours of hospital admission as well as within 24 hours of hospital discharge and at 30 days from 74 participants who presented with a NSTEMI (troponin I >5 ng/ml) or with a STEMI and were enrolled in 2 randomized, double-blind trials of evolocumab and placebo (Evolocumab in Acute Coronary Syndrome [EVACS I]; ClinicalTrials.gov, NCT03515304 and Evolocumab in Patients With STEMI [EVACS II]; ClinicalTrials.gov Identifier: NCT04082442). There was a significant increase from the pretreatment level in the placebo-treated patients, from 64 (41,187) nmol/L to 80 (47, 172) nmol/L at hospital discharge and to 82 (37, 265) at 30 days. This was primarily driven by the results from participants with high Lp(a) at hospital admission (>75 nmol/L) in whom the median increase was 28% as compared with a 10% increase in those with pretreatment Lp(a) of <75 nmol/L. In contrast, there was no significant change from the pretreatment level in the evolocumab-treated patients regardless of pretreatment Lp(a) levels. In conclusion, Lp(a) rises during the peri-infarction and early postinfarction period in patients with acute myocardial infarction. The increase was prevented by a single dose of subcutaneous evolocumab given within 24 hours of hospital admission.
AIMS: Lipoprotein(a) [Lp(a)] levels are generally constant throughout an individual's lifetime, and current guidelines recommend that a single measurement is sufficient to assess the risk of coronary artery disease (CAD). However, it is unclear whether a single measurement of Lp(a) in individuals with acute myocardial infarction (MI) is indicative of the Lp(a) level six months following the event.
METHODS AND RESULTS: Lp(a) levels were obtained from individuals with non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) (n = 99) within 24 h of hospital admission and after six months, who were enrolled in two randomized trials of evolocumab and placebo, and in individuals with NSTEMI or STEMI (n = 9) who enrolled in a small observation arm of the two protocols and did not receive study drug, but whose levels were obtained at the same time points. Median Lp(a) levels increased from 53.5 nmol/L (19, 165) during hospital admission to 58.0 nmol/L (14.8, 176.8) six months after the acute infarction (P = 0.02). Subgroup analysis demonstrated no difference in the baseline, six-month, or change between the baseline and six-month Lp(a) values between the STEMI and NSTEMI groups and between the group which received evolocumab and the group that did not.
CONCLUSION: This study demonstrated that Lp(a) levels in individuals with acute MI are significantly higher six months after the initial event. Therefore, a single measurement of Lp(a) in the peri-infarction setting is not sufficient to predict the Lp(a)-associated CAD risk in the post-infarction period.
REGISTRATION: Evolocumab in Acute Coronary Syndrome Trial [EVACS I] NCT03515304, Evolocumab in Patients with Acute Myocardial Infarction [EVACS II], NCT04082442.
Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators\' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in an important subset of ACS patients, those with non-ST elevation myocardial infarction (NSTEMI) by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.
