Lipoprotein(a) not linked to increased CVD risk in ACS patients after all

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 - Heart

Although the atherogenic lipoprotein(a) [Lp(a)] has been associated with incident cardiovascular disease, its concentration doesn’t predict the risk of ischemic cardiovascular events following acute coronary syndrome (ACS) in patients receiving other therapies, a study published in JAMA Cardiology reports.

According to Gregory G. Schwartz, MD, PhD, and co-authors, Lp(a) has been suggested in the past to promote atherosclerosis, thrombosis and cardiovascular disease (CVD), making its mark in the field as a possible independent risk factor for CVD. Even with epidemiological and genetic data supporting the theory, the consequences of Lp(a) concentration in patients who have suffered ACS is uncertain, Schwartz et al. wrote.

The researchers performed an ad hoc analysis of the dal-Outcomes trial, which used a randomized, double-blind comparison of cholesteryl ester transfer protein inhibitor “dalcetrapid” and placebos in nearly 16,000 patients who had experienced ACS recently. Patients’ progress was tracked between April 2008 and September 2012 at 935 sites across 27 countries, Schwartz and colleagues wrote, with an average follow-up period of 29 months.

Patients who qualified for the study were randomly assigned 600 mg of dalcetrapib per day or a matching placebo drug. Therapies started four to 12 weeks after an index ACS event, the authors said, once patients were clinically stable and had completed their planned coronary revascularization procedures. Since Lp(a) is a positive acute-phase reactant with increased concentration for weeks following ACS, clinicians waited for a period before administering the trial treatments.

The 969 case patients were an average of 63 years old, according to the paper, and 3,170 control patients were also mostly in their early sixties. A majority of the subjects were using contemporary secondary prevention strategies after ACS—97 percent were taking statins, 87 percent were on beta-blockers and numerous others were being treated with angiotensin-converting enzyme or receptor inhibitors, aspirin, platelet P2Y12 antagonists and coronary revascularization.

Lp(a) levels, measured in serum samples and starting at a baseline average of 12.3 mg/dL, didn’t show any association with risk of mortality due to coronary heart disease, major nonfatal coronary events or stroke, Schwartz and his colleagues found—a discovery that questions the utility of lowering Lp(a) levels following ACS.

“Although Lp(a) levels appear to be associated with cardiovascular risk in initially healthy individuals, the present analysis indicates that there is no association between Lp(a) level and risk of ischemic cardiovascular events after ACS,” the authors wrote.

Patients did see small decreases in Lp(a) concentration after three months of treatment, Schwartz et al. reported, regardless of whether those individuals were treated with dalcetrapib or a placebo. The shift in concentration from baseline was marginally greater with dalcetrapib than with the placebo drug.

“Despite other evidence that Lp(a) promotes the progression of atherosclerosis and increases the risk of thrombosis in individuals with high plaque burden, data from the present analysis indicate that the concentration of Lp(a) does not predict the risk of ischemic cardiovascular events in patients with recent ACS,” Schwartz and co-authors wrote. “Nonetheless, it remains to be determined whether a reduction in Lp(a) concentration with new therapies, such as  PCSK9 inhibitors or antisense oligonucleotide to apolipoprotein (a), will thereby result in reduced risk of ischemic cardiovascular events after ACS.”