Coronary Event Risk in FH Remains High After ACS, Despite Statins

Patrice Wendling

August 05, 2016

LUSANNE, SWITZERLAND — Even when treated with high-dose statins, patients with familial hypercholesterolemia (FH) hospitalized for ACS face more than a twofold adjusted higher risk of a recurrent coronary event than patients without FH, new research shows[1].

"We were quite surprised that statins were very well prescribed at discharge [98.6%] but also that after 1 year 70% of patients with FH were still using high-dose statins, which is very good in fact. So these patients can tolerate high-dose statins," lead investigator Dr David Nanchen (University of Lausanne, Switzerland) told heartwire from Medscape.

But despite this use, the mean cholesterol was 120 mg/mL 1 year after ACS hospitalization, and less than 10% of patients achieved the 70-mg/dL LDL-C target.

"This is probably one thing that could explain the high risk of these patients," he said. "Statins are definitely effective, but there is still room to decrease the LDL cholesterol."

The study, published July 27, 2016 in Circulation, notes that novel lipid-lowering drugs like proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors may have a role in further reducing the risk of CVD in patients with FH.

"The problem with these drugs is that they are very expensive, so probably the best initial strategy to prescribe these drugs is to target patients with familial hypercholesterolemia after acute coronary syndrome because they are at high risk of recurrence and they cannot achieve lower cholesterol levels," Nanchen said.

To determine what happens to patients with FH after discharge for ACS, the researchers examined data for 4534 patients in the Special Program University Medicine-Acute Coronary Syndromes (SPUM-ACS) study, a prospective study of consecutive patients hospitalized with ACS in Switzerland.

Data show that FH is currently underdiagnosed, but Nanchen said it "is definitely not a rare disease among patients with acute coronary syndrome." The prevalence reached 5.5%, which may be 10 times higher than in the general population.

The prevalence was 2.5% based on the latest American Heart Association (AHA) definition combining LDL-C >190 mg/dL and family history of a first-degree relative with premature CHD; prevalence reached 5.5% based on the Simon Broome definition (recommended by National Institute for Health and Care Excellence [NICE] guidelines) using total cholesterol >290 mg/dL or LDL-C >190 mg/dL and a personal or family history of premature coronary disease.

A further 18.2% were identified with possible FH and 1.6% with probable/definite FH using the Dutch Lipid Clinic definition, which also uses LDL-C levels along with personal or family history of premature CHD.

Based on AHA, Simon Broome, and Dutch Lipid Clinic definitions, total cholesterol at admission was 270.7, 274.6, and 224.3 mg/dL, respectively, and LDL-C was 224.3, 224.3, and 166.3 mg/dL, respectively.

During the year after discharge, 153 patients died, 217 suffered a fatal or nonfatal MI, and 275 experienced a CV event.

Unadjusted rates of coronary and CV events were similar between patients with and without FH, despite patients with FH being more than 10 years younger.

After multivariable adjustment including age, however, patients with FH had a significantly higher risk of recurrent coronary events compared with those without FH.

Risk of Coronary Event a Year After ACS, Patients With vs Without FH

FH definition HR (95% CI) P
AHA 2.46 (1.07–5.65) 0.034
Simon Broome 2.73 (1.46–5.11) 0.002
Dutch Lipid Clinic (probable/definite FH) 3.53 (1.26–9.94) 0.017

For cardiovascular events, statistical significance was reached only with the Simon Broome definition (HR 2.49, 95% CI 1.43–4.34; P=0.046).

The findings suggest that "a hospitalization for acute coronary syndrome is a very good opportunity to screen and identify patients with familial hypercholesterolemia," Nanchen observed.

Once identified, clinicians should provide FH educational materials, screen family members, and take care of other cardiovascular risk factors, "because we found half of patients with FH were smokers and 40% had hypertension," he added.

The SPUM-ACS cohort is supported by the Swiss National Science Foundation. Nanchen reported no relevant financial relationships. Disclosures for the coauthors are listed in the article.

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