View More 2019, Scientific Sessions, Session Coverage

Experts debate benefits of aggressive lowering of LDL cholesterol

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A pair of experts addressed the ongoing controversy about how intensive therapy should be to lower low-density lipoprotein (LDL) cholesterol during Friday’s session Is Very Aggressive Lowering of LDL Cholesterol Worthwhile?

Steven E. Nissen MD, MACC
Steven E. Nissen, MD, MACC

Arguing in favor of aggressive therapy, Steven E. Nissen, MD, MACC, Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, said studies have shown the benefits of LDL reduction are continuous and extend to extremely low levels.

“Going back about 15 years ago, we started this march toward lower and lower LDL levels,” he said. “One of the key trials was PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), which suggests that achieved LDL-C (cholesterol) levels less than 80 mg/dL might be associated with improved outcomes, compared with achieved levels of 80 to 100 mg/dL.”

Similar results, he said, have been shown in numerous clinical trials.

“Every time we lower LDL, we get more reduction in morbidity and mortality,” Dr. Nissen said. “Compelling evidence from trials in hundreds of thousands of patients demonstrate that reducing LDL-C to very low levels reduces cardiovascular events in broad populations and is extremely safe. We used to say you can’t be too rich or too thin, we now say you can’t be too rich, too thin, or have too low an LDL.”

Sanket Dhruva, MD
Sanket Dhruva, MD, MS

Sanket Dhruva, MD, MS, Assistant Professor of Medicince at the University of California, San Francisco, countered that while results from clinical trials are important, they don’t always reflect “real world” patients.

“Randomized clinical trials are a best-case scenario with tightly controlled conditions that may have run-in periods. While they are the gold standard, they may not mimic what happens in the real world, and observational studies give us a lot more insight into outcomes in the real world,” he said. “We assume, for example, that all patients with diabetes are at equally high risk of cardiovascular disease and should be treated equally aggressively. It should be noted, though, that most clinical trials suggesting benefits from intensive risk factor control involve high-risk patients.”

Dr. Dhruva cited a 2010 study that showed that aggressively lowering LDL-C in diabetes patients led to an average of 1.50 quality adjusted life years (QALY). Reaching target LDL-C levels translated to a mean net gain of less than one QALY in low-risk patients and a mean net gain of 4.1 QALY in high-risk patients.

“Highest risk patients benefit much more compared with low-risk patients. Those with the highest cardiovascular disease risk are accounting for the majority of the benefit,” he said. “This means that benefit is related to baseline risk, and not all patients with diabetes should be treated aggressively. For low risk patients, there’s little benefit to gain.”