乌鸦传媒

Level of lipoprotein(a), or Lp(a), doesn't predict recurrent cardiovascular events immediately after an acute coronary syndrome (ACS) in the context of good medical therapy, according to an ad hoc analysis of the dal-Outcomes trial.

Median Lp(a) level did not differ substantially between those who did and did not have subsequent events, Gregory Schwartz, MD, PhD, of Denver's Veterans Affairs Medical Center, and colleagues reported online in JAMA Cardiology.

In a case-cohort regression analysis, having twice as much Lp(a) over a median 29 months of follow-up (adjusted HR 1.01, 95% CI 0.96-1.06). And even the highest deciles were not associated with significantly greater risk.

"These findings call into question whether treatment specifically targeted to reduce Lp(a) levels would thereby lower the risk for ischemic cardiovascular events after ACS," the researchers wrote.

Importantly, the study population was highly exposed to medical therapy: 97% got statins, 87% beta blockers, 80% ACE inhibitors, 97% aspirin, and 89% clopidogrel (Plavix) and other platelet P2Y12 inhibitors. In total, 89% received coronary revascularization for the index ACS event.

"In studies that specifically evaluated patients with ACS, the congruent neutral findings from the and the present analysis suggest that prognosis is dominated by factors other than Lp(a) concentration or that any influence of Lp(a) level is nullified by the prevalent use of high-intensity statin therapy, dual antiplatelet therapy, and coronary revascularization procedures," Schwartz's group said.

"Moreover, the corresponding findings from the PROVE-IT trial (with Lp[a] levels measured approximately 1 week after ACS) and from the present analysis (with the Lp[a] level measured 4 to 12 weeks after ACS) suggest that acute-phase effects on Lp(a) levels are unlikely to influence any association of Lp(a) level with cardiovascular outcomes; instead, the composite of the data on ACS indicate that no such association exists."

The investigators conceded that perhaps PCSK9 inhibitors and other therapies may reduce Lp(a) concentrations to the point that they also meaningfully reduce the risk of ischemic cardiovascular events after ACS.

Lp(a), a transporter of cholesterol and triglycerides in the bloodstream, is thought to promote atherosclerosis and thrombosis.

Schwartz and colleagues performed an ad hoc analysis of the dal-Outcomes trial, which randomized patients to the cholesteryl ester transfer protein inhibitor dalcetrapib or placebo beginning 4 to 12 weeks after ACS. They measured Lp(a) in serum samples after ACS and again at 3 months by immunoturbidimetric assay.

By the end of follow-up, there were 969 case patients (those who experienced a primary cardiovascular outcome) and 3,170 randomly-matched control patients (those who were event-free after experiencing the index ACS). Participants were mostly white men.

"Its limitations include the possibility that the analysis was underpowered to detect an association of Lp(a) level with cardiovascular outcomes restricted to the upper range of Lp(a) concentrations," the authors said of their study.

"Other limitations are those inherent to case-cohort studies, which are subject to confounding because only a subset of the entire trial cohort had biomarker measurements. Matching and covariate adjustments were used to account for the most likely confounders, but potential confounding by other unmeasured covariates cannot be excluded," they acknowledged.

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