High-Intensity Statin Therapy Offers Survival Benefit Over Moderate-Intensity Statins in CVD Patients

High-intensity statin therapy is associated with a “small but significant” reduction in the risk of all-cause mortality when compared with moderate-intensity statin therapy in individuals with existing atherosclerotic cardiovascular disease, a new analysis shows.

Treatment with a high-intensity statin, which includes rosuvastatin 20 or 40 mg and atorvastatin 40 or 80 mg, was associated with a 9% reduction in the risk of death at 1 year compared with taking a moderate-intensity statin. For those treated with the maximal dose of rosuvastatin or atorvastatin, there was a 10% reduction in the risk of death when compared with those taking submaximal doses.

Based on their data, lead investigator Fatima Rodriguez, MD (Stanford University, CA), told TCTMD that physicians “should really push the high-intensity statin in secondary prevention and not only that but also the highest dose of high-intensity statins, as they offer a survival advantage and should really be the target in patients who are able to tolerate it.”    

The study was published November 9, 2016, in JAMA Cardiology.

Conflicting Recommendations for VA Patients

In 2013, the American College of Cardiology (ACC) and American Heart Association (AHA) released guidelines for the treatment of cholesterol and recommended the use of high-intensity statin therapy in all patients with atherosclerotic cardiovascular disease regardless of their LDL cholesterol levels.

Rodriguez noted that the US Department of Veterans Affairs (VA) and Department of Defense (DoD) have their own separate dyslipidemia guidelines. These recommend moderate-intensity statins for most patients with cardiovascular disease, reserving high-intensity statins for high-risk secondary-prevention subgroups. The VA/DoD writing committee felt the data are not strong enough to recommend high-intensity statins for all secondary-prevention patients and also had concerns about statin intolerance.

Given those two separate recommendations, the researchers evaluated the association between all-cause mortality and statin intensity in 509,766 patients with documented cardiovascular disease enrolled in the VA healthcare system. Overall, there was graded association between statin intensity and death, even among older individuals. The 1-year mortality rate was 4.0% for those taking a high-intensity statin, 4.8% for those taking a moderate-intensity statin (atorvastatin 10-20 mg, fluvastatin 80 mg, lovastatin 40 mg, pitavastatin 2-4 mg, pravastatin 40-80 mg, rosuvastatin 5-10 mg, and simvastatin 20-40 mg), 5.7% for those taking a low-intensity statin, and 6.6% for those not taking any statin (P < 0.001).

“It’s very interesting that despite doing multiple statistical analyses, including adjusting for the propensity to be on a statin and excluding patients not on a statin to account for statin intolerance, there was still a very clear dose-response relationship,” said Rodriguez. “When you see this kind of dose-response relationship, it really suggests—again, it’s an observational study—that the effect we’re seeing is real.”

To TCTMD, Rodriguez there might be a sense of complacency among physicians, even among cardiologists, when treating patients with existing atherosclerotic cardiovascular disease. “The patient might be on a moderate-intensity statin and their LDL cholesterol is OK, so they’ll probably just leave it as it is,” she said. “But now this is compelling data that suggests we really should push high-intensity statins in these patients. One thing we also document in this study, and there are other papers showing it, too, but the use of high-intensity statins is quite low in this population.”

Just 29.6% of patients included in the analysis were taking a high-intensity statin while 45.6% were taking a moderate-intensity statin. In addition, 6.7% were being treated with a low-intensity statin and 18.2% were not taking statin therapy at all.

Benefit Observed in Older Patients   

Among individuals aged 76 to 84 years, a group in whom the 2013 ACC/AHA cholesterol guidelines recommend moderate-intensity statins, there was a 9% reduction in the risk of death at 1 year among the high-intensity statin users compared with those taking a moderate-intensity statin. Rodriguez said that with an older population, physicians may worry about polypharmacy and their ability to metabolize medications.

“We completely understand that concern, but some of those patients are the ones at highest risk and it would make sense to treat them aggressively to prevent an event, especially given our data,” she said.

In an editor’s note, Robert Bonow, MD, and Clyde Yancy, MD (Northwestern Medical, Chicago, IL), point out that the evidence base for high-intensity statin therapy in those 75 years and older is small—such patients are not enrolled frequently in clinical trials—and for that reason the ACC/AHA guidelines recommend only-moderate intensity statins for secondary prevention. The finding of equivalent benefit in the older cohort, with no excessive risks, should lead to more randomized controlled trials in these older patients, they state.

“Clearly the prescription of statin therapy and its intensity remains highly individualized, but we find these findings confirmatory that high-intensity statin therapy when appropriate is beneficial for secondary prevention, and these benefits are seen even in older persons,” write the editors. “These data, along with close adherence to the prevailing guidelines, offer effective strategies to reduce death and disability owing to death and disability from [atherosclerotic cardiovascular disease].”

Michael O’Riordan is the Managing Editor for TCTMD. He completed his undergraduate degrees at Queen’s University in Kingston, ON, and…

Read Full Bio
  • Rodriguez F, Maron DJ, Knowles JW, et al. Association between intensity of statin therapy and mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiology. 2016;Epub ahead of print.

  • Bonow RO, Yancy CW. High-intensity statins for secondary prevention. JAMA Cardiology. 2016;Epub ahead of print.

  • Rodriguez and colleagues report no conflicts of interest.
  • Bonow and Yancy report no conflicts of interest.