Abstract 5765: 9p21 Genetic Variant and Benefit From Intensive Statin Therapy After an Acute Coronary Syndrome
Background Genetic variation at 9p21 has been associated with a greater risk of MI. The relationship of this locus to risk of recurrent coronary events in patients with ACS and to benefit from intensive statin therapy is unknown.
Methods We studied 2029 pts in PROVE IT-TIMI 22, a trial of intensive (atorvastatin 80 mg/d) vs moderate (pravastatin 40 mg/d) statin therapy after recent ACS. Cox regression was used to assess risk of recurrent coronary events associated with 9p21 rs1333049 “C” allele adjusting for clinical risk factors and to test for an interaction between statin therapy and rs1333049, as well as KIF6 719Arg, a gene variant previously shown to be associated with clinical benefit of statins.
Results Among those treated with moderate statin therapy, the adj HR for CHD/MI over 2 yrs was 1.35 (95% CI 0.80 –2.28) for carriers (75% of pts) vs non-carriers. Benefit from intensive vs moderate statin therapy was significantly greater among rs1333049 “C” allele carriers than non-carriers (Fig⇓). In a multilocus model, both rs1333049 and KIF6 variants modified statin therapy (Pinteraction 0.035 & 0.029), and a particularly large benefit of intensive statin therapy was seen in carriers of both variants (HR 0.32, 95% CI 0.17– 0.59, P<0.0001).
Conclusion The rs1333049 variant at 9p21 is associated with a trend towards increased risk of recurrent CHD/MI in patients who receive moderate statin therapy following an ACS, consistent with the risk seen for MI in population studies. Carriers of the rs1333049 “C” and the KIF6 719Arg variants appear to receive significantly greater benefit from intensive versus moderate statin therapy. Further study of these pharmacogenetic interactions is warranted.