Strategies to Lower Cardiovascular Risk: What the Latest Evidence Shows
Despite the many double-blind, placebo-controlled trials that have demonstrated the efficacy of statins in reducing the risk of cardiovascular events, a large number of patients who are treated with these drugs still experience such events. This may be because patients who require intensive lipid lowering are not receiving adequate dosages of statins.
Here I report on recent study results that illustrate the problem of undertreatment. I also discuss evidence that greater decreases in low-density lipoprotein cholesterol (LDLC) levels are associated with greater reductions in the incidence of cardiovascular events. In addition, I present the results of studies of novel therapies that may someday reduce the toll of coronary events (Box).
UNDERTREATMENT: A COMMON PROBLEM
In a study by Jönsson and colleagues,1 a total of 9789 patients were given lipid-lowering therapy for 10 years. During the first year of treatment, only 5% of patients were titrated to a higher dose; overall, 70% of the patients did not attain lipid goals. Those who did reach their goals experienced fewer events and incurred lower health care costs.
Herbert and associates2 reported that a significant number of patients with documented coronary artery disease are not given lipid-lowering drugs at all. In an analysis of 6914 patients who underwent coronary artery bypass grafting between January 2000 and July 2003, only 32% of patients who received 2 types of cardiovascular drugs on discharge were given a lipid- lowering agent as one of their 2 medications.2
EVIDENCE THAT “LOWER IS BETTER”
The REVERSing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study, which included 502 patients with stable coronary artery disease (CAD), demonstrated that atorvastatin, 80 mg/d, provided greater LDL-C reduction than pravastatin, 40 mg/d; this greater decrease was associated with less progression of CAD as measured by intravascular ultrasonography.3
The Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE-IT) trial compared intensive (atorvastatin, 80 mg/d) and more moderate (pravastatin, 40 mg/d) lipid-lowering therapy in 4162 patients hospitalized at major US medical centers for an acute coronary syndrome. After a mean follow-up of 2 years, intensive statin treatment had lowered LDL-C levels to a median of 62 mg/dL, compared with a median of 95 mg/dL with standard lipid lowering (P < .001).4 Patients who received the intensive lipidlowering regimen experienced a 16% greater reduction in risk of death or major cardiovascular events than those who received moderate lipid-lowering therapy (P = .005).4 Interestingly, more than half of the patients enrolled in the trial had preexisting CAD, diabetes mellitus, or peripheral vascular disease— all of which are major indications for statin therapy—but only 25% of the patients in the trial were receiving statin therapy at baseline.
Taken together, the REVERSAL and PROVE-IT trials foreshadowed an increased awareness of the need for appropriate but aggressive lipid-lowering therapy. An LDL-C goal of less than 70 mg/dL was proposed as a therapeutic option in very high-risk patients in a recent update to the National Cholesterol Education Program Adult Treatment Panel III guidelines. 5 However, there is insufficient evidence to recommend this treatment goal in less high-risk patients.
The results of the Treating to New Targets (TNT) trial, which are expected to be reported at the November 2004 meeting of the American Heart Association, will help experts reach a definite decision about changing the guidelines for this larger patient population. The TNT trial has randomized 10,003 patients to double-blind treatment with either atorvastatin, 10 mg, or atorvastatin, 80 mg; the average followup is 5 years.6 In the meantime, practitioners are advised to focus on helping patients achieve an LDL-C level of 100 mg/dL or lower. Fewer than 50% of all patients who have had an acute myocardial infarction currently reach this goal, which indicates that better compliance is needed.
OPTIONS FOR AGGRESSIVE LIPID LOWERING
To meet the need for more aggressive lipid-lowering therapy, the newest statin, rosuvastatin, might be used. There is evidence that rosuvastatin is the most efficacious for lowering total cholesterol, LDLC, and non–high-density lipoprotein cholesterol.7 A randomized, parallel-group, open-label trial compared rosuvastatin with 3 other currently marketed statins and demonstrated that rosuvastatin, 10 to 40 mg/d, produced LDL-C reductions ranging from 46% to 55%, compared with reductions of 37% to 51% for atorvastatin, 10 to 80 mg/d; 28% to 46% for simvastatin, 10 to 80 mg/d; and 20% to 30% for pravastatin, 10 to 40 mg/d.8
Combination therapy that includes fibrates, niacin, and/or ezetimibe in addition to a statin can sometimes be helpful as well. Significant results can also be achieved with the addition of such nonpharmacologic therapies as soluble fiber, stanol-ester margarine, and sterol-enriched orange juice.