Some patients with diabetes may not benefit from aggressive management of cardiovascular risk factors and some may even be harmed, according to a statistical model based on a government health survey.…
Intensive, stepped-care management of dyslipidemia and hypertension led to gains of 1 to 1.5 quality-adjusted-life-years (QALY) in people who had a life expectancy of 10 to 11 years. But adjustment for potential harms of treatment reduced the benefits.
Only the patients at highest risk benefited from intensification beyond the first step of management protocols, suggesting that current clinical guidelines often recommend inherently flawed strategies, authors of the study reported.
Senior author Justin W. Timbie, PhD, of the RAND Corp. in Arlington, Va., wrote, “Below average to average-risk patients seem to receive virtually no net benefit from titrating beyond standard dose of a statin and two to three blood pressure medications, even if commonly recommended LDL-C and blood pressure goals have not been met.”
“Given the large set of factors that moderate the benefit of treatment intensification … the diminishing effects of combination therapy, and increasing polypharmacy and adverse effects, we recommend a strategy of tailoring treatments to individual patients on the basis of their expected benefit of intensifying treatment. Current treatment approaches that encourage uniformly lowering risk factors to common target levels can be both inefficient and cause unnecessary harm.”
Almost all clinical guidelines for diabetes recommend aggressive treatment of LDL cholesterol and blood pressure. However, the recommendations are based on averaging of benefits from clinical trials, the authors wrote.
Tailoring treatment to individual patient risk has received little or no attention in diabetes risk management, apparently because of “an implicit assumption that all patients with diabetes are at equally high risk, requiring all patients to be treated aggressively.”
In fact, the benefit of intensified stepped-care therapy or treating to targets could vary substantially across the diabetic population, depending on the distribution of cardiovascular disease risk in the population, the authors continued.
Recent substudies of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed no survival advantage and suggested possible harm associated with a blanket approach to aggressive treatment of dyslipidemia and high blood pressure (N Engl J Med 2010; 362: 1563-74, N Engl J Med 2010; 362: 1575-85). Nonetheless, some high-risk patients might still benefit from an aggressive strategy.
In an effort to clarify the role of aggressive risk-factor management in diabetic patients, Timbie and co-authors designed a study to assess the variability in benefit and harm associated with treating to target. They identified adult diabetic participants in the third National Health and Nutrition Examination Survey (NHANES III) and developed models to simulate treat-to-target strategies for LDL and blood pressure.
The LDL target was 100 mg/dL and the blood pressure target was 130/80 mm Hg. Patients could progress through five titrations of statin therapy for LDL and eight titrations of antihypertensive therapy. The models incorporated adverse effects of treatment and the risks and burdens of polypharmacy.
Treating to the specified target for LDL resulted in a gain of 1.50 QALY and 1.35 QALY for treatment to the blood pressure target. After accounting for treatment-related harms, the QALY gain declined to 1.42 for LDL and 1.16 for blood pressure.
“Most of the total benefit was limited to the first few steps of medication intensification or to tight control for a limited group of very high-risk patients,” the authors wrote.
“Intensifying beyond the first step for LDL or third step for blood pressure resulted in either limited benefit or net harm for patients with below-average risk,” they added.
Statistical modeling has inherent limitations in its ability to simulate reality. Even so, “the lessons to be gleaned from this simulation are profound,” Andrew L. Avins, MD, of Kaiser Permanente Northern California in Oakland, wrote in an editorial.
“Most important, the results starkly challenge some fundamental assertions regarding the appropriate treatment of patients with diabetes mellitus. Over the years, practice guidelines have advocated increasingly tighter control of blood glucose and cardiovascular risk factors, often relying on logical inference to extend thresholds beyond the available empirical evidence.”
“The more and more tightly risk factors are controlled, the less benefit there will be in treating each additional risk factor,” Avins continued. “The failure to account for this effect results in substantial overtreatment. Despite the fact that this phenomenon has been known for many years, it is generally ignored, to the detriment of our patients and our limited healthcare resources.”
The principles reflected in the model by Timbie and colleagues apply to virtually all preventive interventions.
“One wonders why such examinations are not generally incorporated into the guideline development process rather than, as in this case, conducted in response to it,” Avins concluded.
- Note that this study found that most patients with diabetes do not benefit from an aggressive, stepped-care approach to managing cardiovascular risk factors.
- Note that the findings are based on a statistical model, not a prospective clinical trial.
Timbie JW, et al “Variation in the net benefit of aggressive cardiovascular risk factor control aceross the U.S. population of patients with diabetes mellitus” Arch Intern Med June 2010; 170: 1037-44.