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CHICAGO – according to the results of the ANITSCHKOW study, Erik S. Stroes, MD, PhD, reported at the American Heart Association scientific sessions.
“The reality is that for now we don’t have any drugs to significantly lower elevated Lp(a),” he said. “We can identify patients with elevated Lp(a), but we don’t have a clue how to treat them.”
Elevated Lp(a) is a highly prevalent lipid abnormality. It induces arterial wall inflammation, a known predictor of future cardiovascular events. The monoclonal antibodies that inhibit PCSK9 (proprotein convertase subtilisin/kexin type 9) dramatically reduce LDL cholesterol and also reduce arterial wall inflammation. In the published studies, PCSK9 inhibitors also reduced Lp(a) by an average of 27%; however, most participants in those studies had isolated high LDL with a normal or slightly elevated Lp(a).
ANITSCHKOW was the first double-blind, randomized, placebo-controlled study to look at the effects of a PCSK9 inhibitor – in this case, evolocumab (Repatha) – in patients with severe elevations in both LDL and Lp(a). The results proved disappointing yet informative, according to Dr. Stroes, professor of internal medicine and a vascular medicine specialist at the University of Amsterdam.
The 16-week, 14-site trial included 128 Dutch, American, and Canadian patients with a mean baseline LDL of 146 mg/dL and a median Lp(a) of 202 nmol/L who were randomized to monthly subcutanous injections of evolocumab at 420 mg or placebo. All participants had evidence of significant arterial wall inflammation at baseline as measured by PET-CT. Of the subjects, 54% were on statin therapy.
Evolucumab achieved a placebo-subtracted 61% reduction in LDL to 60 mg/dL but a mere 14% reduction in Lp(a) to 188 nmol/L, still far in excess of the 50 nmol/L cutoff defining elevated Lp(a).
The primary endpoint was change in arterial wall inflammation from baseline to week 16 as measured using PET-CT. Based upon the results of other studies showing a 3.3% drop in arterial wall inflammation for every 10% reduction in LDL, Dr. Stroes and his coinvestigators expected to see a 20% decrease in arterial wall inflammation in the evolocumab group. Instead, they found a mere 8.4% reduction, which wasn’t significantly different than in placebo-treated controls. And there was no difference in arterial wall inflammation between the group on concomitant statin therapy and those who weren’t.
The implication is that the residual Lp(a) elevation despite PCSK9 inhibitor therapy might explain the discrepancy, compared with previous studies in which LDL lowering did reduce arterial wall inflammation, according to Dr. Stroes.
“Persistent arterial wall inflammation on PET-CT after evolocumab, potentially related to persistent Lp(a) elevation, implies the need for additional therapies to decrease the proinflammatory state in Lp(a) elevation,” he observed.
Lp(a) in the spotlight
An elevated Lp(a) of 50 nmol/L or more is present in 20% of the general population, according to a Danish study. More than 70% of a person’s Lp(a) level is genetically driven. And a genetically driven elevated Lp(a) has been shown to be associated with a twofold to fourfold increased risk of cardiovascular events.
Moreover, other investigators have shown that a severely elevated Lp(a) (greater than 180 nmol/L) poses a cardiovascular risk comparable with that of heterozygous familial hypercholesterolemia and is present in 1 in 100 individuals.
“We spend a lot of time on familial hypercholesterolemia, and we should. But mind you, this severe Lp(a) elevation is more frequent than heterozygous FH,” Dr. Stroes said.
Session cochair Robert H. Eckel, MD, asked the audience for a show of hands by those who regularly measure Lp(a) in their patients. Very few hands were raised.
“I measure Lp(a) frequently, and I think it’s a very important risk factor,” declared Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.
The ANITSCHKOW study was sponsored by Amgen. Dr. Stroes reported receiving institutional research grants from and serving as a paid speaker for Amgen, Merck, Novartis, and Regeneron.
CHICAGO – according to the results of the ANITSCHKOW study, Erik S. Stroes, MD, PhD, reported at the American Heart Association scientific sessions.
“The reality is that for now we don’t have any drugs to significantly lower elevated Lp(a),” he said. “We can identify patients with elevated Lp(a), but we don’t have a clue how to treat them.”
Elevated Lp(a) is a highly prevalent lipid abnormality. It induces arterial wall inflammation, a known predictor of future cardiovascular events. The monoclonal antibodies that inhibit PCSK9 (proprotein convertase subtilisin/kexin type 9) dramatically reduce LDL cholesterol and also reduce arterial wall inflammation. In the published studies, PCSK9 inhibitors also reduced Lp(a) by an average of 27%; however, most participants in those studies had isolated high LDL with a normal or slightly elevated Lp(a).
ANITSCHKOW was the first double-blind, randomized, placebo-controlled study to look at the effects of a PCSK9 inhibitor – in this case, evolocumab (Repatha) – in patients with severe elevations in both LDL and Lp(a). The results proved disappointing yet informative, according to Dr. Stroes, professor of internal medicine and a vascular medicine specialist at the University of Amsterdam.
The 16-week, 14-site trial included 128 Dutch, American, and Canadian patients with a mean baseline LDL of 146 mg/dL and a median Lp(a) of 202 nmol/L who were randomized to monthly subcutanous injections of evolocumab at 420 mg or placebo. All participants had evidence of significant arterial wall inflammation at baseline as measured by PET-CT. Of the subjects, 54% were on statin therapy.
Evolucumab achieved a placebo-subtracted 61% reduction in LDL to 60 mg/dL but a mere 14% reduction in Lp(a) to 188 nmol/L, still far in excess of the 50 nmol/L cutoff defining elevated Lp(a).
The primary endpoint was change in arterial wall inflammation from baseline to week 16 as measured using PET-CT. Based upon the results of other studies showing a 3.3% drop in arterial wall inflammation for every 10% reduction in LDL, Dr. Stroes and his coinvestigators expected to see a 20% decrease in arterial wall inflammation in the evolocumab group. Instead, they found a mere 8.4% reduction, which wasn’t significantly different than in placebo-treated controls. And there was no difference in arterial wall inflammation between the group on concomitant statin therapy and those who weren’t.
The implication is that the residual Lp(a) elevation despite PCSK9 inhibitor therapy might explain the discrepancy, compared with previous studies in which LDL lowering did reduce arterial wall inflammation, according to Dr. Stroes.
“Persistent arterial wall inflammation on PET-CT after evolocumab, potentially related to persistent Lp(a) elevation, implies the need for additional therapies to decrease the proinflammatory state in Lp(a) elevation,” he observed.
Lp(a) in the spotlight
An elevated Lp(a) of 50 nmol/L or more is present in 20% of the general population, according to a Danish study. More than 70% of a person’s Lp(a) level is genetically driven. And a genetically driven elevated Lp(a) has been shown to be associated with a twofold to fourfold increased risk of cardiovascular events.
Moreover, other investigators have shown that a severely elevated Lp(a) (greater than 180 nmol/L) poses a cardiovascular risk comparable with that of heterozygous familial hypercholesterolemia and is present in 1 in 100 individuals.
“We spend a lot of time on familial hypercholesterolemia, and we should. But mind you, this severe Lp(a) elevation is more frequent than heterozygous FH,” Dr. Stroes said.
Session cochair Robert H. Eckel, MD, asked the audience for a show of hands by those who regularly measure Lp(a) in their patients. Very few hands were raised.
“I measure Lp(a) frequently, and I think it’s a very important risk factor,” declared Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.
The ANITSCHKOW study was sponsored by Amgen. Dr. Stroes reported receiving institutional research grants from and serving as a paid speaker for Amgen, Merck, Novartis, and Regeneron.
CHICAGO – according to the results of the ANITSCHKOW study, Erik S. Stroes, MD, PhD, reported at the American Heart Association scientific sessions.
“The reality is that for now we don’t have any drugs to significantly lower elevated Lp(a),” he said. “We can identify patients with elevated Lp(a), but we don’t have a clue how to treat them.”
Elevated Lp(a) is a highly prevalent lipid abnormality. It induces arterial wall inflammation, a known predictor of future cardiovascular events. The monoclonal antibodies that inhibit PCSK9 (proprotein convertase subtilisin/kexin type 9) dramatically reduce LDL cholesterol and also reduce arterial wall inflammation. In the published studies, PCSK9 inhibitors also reduced Lp(a) by an average of 27%; however, most participants in those studies had isolated high LDL with a normal or slightly elevated Lp(a).
ANITSCHKOW was the first double-blind, randomized, placebo-controlled study to look at the effects of a PCSK9 inhibitor – in this case, evolocumab (Repatha) – in patients with severe elevations in both LDL and Lp(a). The results proved disappointing yet informative, according to Dr. Stroes, professor of internal medicine and a vascular medicine specialist at the University of Amsterdam.
The 16-week, 14-site trial included 128 Dutch, American, and Canadian patients with a mean baseline LDL of 146 mg/dL and a median Lp(a) of 202 nmol/L who were randomized to monthly subcutanous injections of evolocumab at 420 mg or placebo. All participants had evidence of significant arterial wall inflammation at baseline as measured by PET-CT. Of the subjects, 54% were on statin therapy.
Evolucumab achieved a placebo-subtracted 61% reduction in LDL to 60 mg/dL but a mere 14% reduction in Lp(a) to 188 nmol/L, still far in excess of the 50 nmol/L cutoff defining elevated Lp(a).
The primary endpoint was change in arterial wall inflammation from baseline to week 16 as measured using PET-CT. Based upon the results of other studies showing a 3.3% drop in arterial wall inflammation for every 10% reduction in LDL, Dr. Stroes and his coinvestigators expected to see a 20% decrease in arterial wall inflammation in the evolocumab group. Instead, they found a mere 8.4% reduction, which wasn’t significantly different than in placebo-treated controls. And there was no difference in arterial wall inflammation between the group on concomitant statin therapy and those who weren’t.
The implication is that the residual Lp(a) elevation despite PCSK9 inhibitor therapy might explain the discrepancy, compared with previous studies in which LDL lowering did reduce arterial wall inflammation, according to Dr. Stroes.
“Persistent arterial wall inflammation on PET-CT after evolocumab, potentially related to persistent Lp(a) elevation, implies the need for additional therapies to decrease the proinflammatory state in Lp(a) elevation,” he observed.
Lp(a) in the spotlight
An elevated Lp(a) of 50 nmol/L or more is present in 20% of the general population, according to a Danish study. More than 70% of a person’s Lp(a) level is genetically driven. And a genetically driven elevated Lp(a) has been shown to be associated with a twofold to fourfold increased risk of cardiovascular events.
Moreover, other investigators have shown that a severely elevated Lp(a) (greater than 180 nmol/L) poses a cardiovascular risk comparable with that of heterozygous familial hypercholesterolemia and is present in 1 in 100 individuals.
“We spend a lot of time on familial hypercholesterolemia, and we should. But mind you, this severe Lp(a) elevation is more frequent than heterozygous FH,” Dr. Stroes said.
Session cochair Robert H. Eckel, MD, asked the audience for a show of hands by those who regularly measure Lp(a) in their patients. Very few hands were raised.
“I measure Lp(a) frequently, and I think it’s a very important risk factor,” declared Dr. Eckel, professor of medicine and director of the lipid clinic at University of Colorado Hospital, Aurora.
The ANITSCHKOW study was sponsored by Amgen. Dr. Stroes reported receiving institutional research grants from and serving as a paid speaker for Amgen, Merck, Novartis, and Regeneron.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: Evolocumab has no effect on arterial wall inflammation in patients with severely elevated Lp(a).
Major finding: Median Lp(a) declined modestly from 202 nmol/L to 188 nmol/L in response to evolocumab.
Study details: This multicenter, 16-week, double-blind, placebo-controlled study included 128 patients with both elevated LDL and Lp(a).
Disclosures: The ANITSCHKOW study was sponsored by Amgen. The presenter reported receiving institutional research grants from and serving as a paid speaker for Amgen, Merck, Novartis, and Regeneron.