Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes .
Although no overall benefit was noted in all-cause or cardiovascular mortality , such benefit may be achievable in patients with higher baseline low-density lipoprotein cholesterol
BACKGROUND We sought to examine the efficacy and safety of 2 PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitors : alirocumab and evolocumab .
Determinants of Residual Risk in Secondary Prevention Patients Treated With High- Versus Low-Dose Statin Therapy: The Treating to New Targets (TNT) Study
Background — Cardiovascular events occur among  statin-treated patients , albeit at lower rates . Risk factors for this “ residual risk ” have not been studied comprehensively . We aim ed to identify determinants of this risk above and beyond lipid-related risk factors . Methods and Results — A total of 9251 coronary patients with low-density lipoprotein cholesterol < 130 mg/dL r and omized to double-blind atorvastatin 10 or 80 mg/d in the Treating to New Targets ( TNT ) study had complete on-treatment 1-year lipid data . Median follow-up was 4.9 years . The primary end point was major cardiovascular events ( n=729 ) : coronary death , nonfatal myocardial infa rct ion , resuscitation after cardiac arrest , or fatal or nonfatal stroke . Multivariable determinants of increased risk were older age ( adjusted hazard ratio [ aHR ] , 1.13 per 1 SD [ 8.8 years ] ; 95 % confidence interval [ CI ] , 1.04–1.23 ) , increased body mass index ( aHR , 1.09 ; 95 % CI , 1.02–1.17 per 4.5 kg/m2 ) , male sex ( aHR , 1.33 ; 95 % CI , 1.07–1.65 ) , hypertension ( aHR , 1.38 ; 95 % CI , 1.17–1.63 ) , diabetes mellitus ( aHR , 1.33 ; 95 % CI , 1.11–1.60 ) , baseline apolipoprotein B ( aHR , 1.19 ; 95 % CI , 1.11–1.28 per 19 mg/dL ) , and blood urea nitrogen ( aHR , 1.10 ; 95 % CI , 1.03–1.17 per 4.9 mg/dL ) , in addition to current smoking , prior cardiovascular disease , and calcium channel blocker use . Determinants of decreased risk were high-dose statin ( aHR , 0.82 ; 95 % CI , 0.70–0.94 ) , aspirin use ( aHR , 0.67 ; 95 % CI , 0.56–0.81 ) , and baseline apolipoprotein A-I ( aHR , 0.91 ; 95 % CI , 0.84–0.99 per 25 mg/dL ) . On-treatment 1-year lipids or apolipoproteins were not additionally associated with risk in multivariable models . Known baseline variables performed moderately well in discriminating future cases from noncases ( Harrell c index=0.679 ) . Conclusions — Determinants of residual risk in statin-treated secondary prevention patients included lipid-related and nonlipid factors such as baseline apolipoproteins , increased body mass index , smoking , hypertension , and diabetes mellitus . A multifaceted prevention approach should be underscored to address this risk . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique identifier : NCT00327691
Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes .
Although no overall benefit was noted in all-cause or cardiovascular mortality , such benefit may be achievable in patients with higher baseline low-density lipoprotein cholesterol
BACKGROUND We sought to examine the efficacy and safety of 2 PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitors : alirocumab and evolocumab .