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Higher intensity of statin therapy associated with lower risk of death in patients with atherosclerotic cardiovascular disease

November 09, 2016

Among more than 500,000 patients with atherosclerotic cardiovascular disease, researchers found an inverse association between intensity of statin therapy and mortality, with patients who received high-intensity statins having the greatest reductions in risk of death, according to a study published online by JAMA Cardiology.

Statin therapy remains the cornerstone for the prevention of atherosclerotic cardiovascular disease (ASCVD). Many large, randomized trials have shown that the use of statins significantly reduces the likelihood of future cardiovascular events and mortality in diverse populations. Nevertheless, statin therapy in general, and high-intensity statin therapy in particular, is underused in patients with established ASCVD. The Veterans Affairs (VA) health care system has released dyslipidemia guidelines that recommend moderate-intensity statins for most patients with ASCVD, citing insufficient evidence for recommending high-intensity statin therapy except in some subgroups of patients at high risk for ASCVD.

Paul A. Heidenreich, M.D., M.S., of Stanford University, Stanford, Calif., and colleagues examined 1-year cardiovascular mortality by intensity of statin therapy among patients age 21 to 84 years with ASCVD treated in the Veterans Affairs health care system. Intensity of statin therapy was defined by the 2013 American College of Cardiology/American Heart Association guidelines, and use was defined as a filled prescription in the prior 6 months.

The study sample included 509,766 eligible adults with ASCVD at study entry (average age, 69 years), including 30 percent receiving high-intensity statin therapy (defined as atorvastatin, 40 to 80 mg, rosuvastatin, 20 to 40 mg, simvastatin, 80 mg), 46 percent receiving moderate-intensity statin therapy (atorvastatin, 10 to 20 mg, fluvastatin, 40 mg twice a day or 80 mg once a day [extended-release formulation], lovastatin, 40 mg, pitavastatin, 2 to 4 mg, pravastatin, 40 to 80 mg, rosuvastatin, 5 to 10 mg, and simvastatin, 20 to 40 mg), 6.7 percent receiving low-intensity statin therapy (fluvastatin, 20 to 40 mg, lovastatin, 20 mg, simvastatin, 10 mg, pitavastatin, 1 mg, and pravastatin, 10 to 20 mg), and 18 percent receiving no statins.

During an average follow-up of 492 days, there was a graded association between intensity of statin therapy and mortality, with 1-year mortality rates of 4 percent for those receiving high-intensity statin therapy, 4.8 percent for those receiving moderate-intensity statin therapy, 5.7 percent for those receiving low-intensity statin therapy, and 6.6 percent for those receiving no statin. The researchers also found that the maximal doses of high-intensity statins (atorvastatin, 80 mg, and rosuvastatin, 40 mg) conferred the greatest survival advantage compared with submaximal doses of high-intensity statins. The benefits of high-intensity statins were consistent for those older than 75 years compared with younger patients.

"We evaluated the real-world practice of statin use by intensity and its association with all-cause mortality in a national sample of patients with ASCVD in the VA health system. We found an inverse graded association between intensity of statin therapy and mortality. These findings suggest there is a substantial opportunity for improvement in the secondary prevention of ASCVD through optimization of intensity of statin therapy," the authors write.
(doi:10.1001/jamacardio.2016.4052. Available pre-embargo at

Editor's Note: The study was conducted using departmental funds from the Department of Medicine, Stanford University, and Medical Service, Veterans Affairs Palo Alto Health Care System. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

The JAMA Network Journals

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