What’s new in lipids?

Highlight: EPCCS satellite symposium held at WONCA meeting in September 2008 in Istanbul
Cardiovascular disease (CVD) is one of the leading causes of death and disability worldwide and its prevalence is predicted to increase in the next decade. Elevated low-density lipoprotein cholesterol (LDL-C) levels are the most important modifiable risk factor for CVD, followed by smoking, stress, diabetes mellitus, hypertension and obesity (Yusuf et al, INTERHEART study, Lancet 2004). A highly significant correlation exists between mean LDL-C reduction and CVD reduction. In fact, an LDL-C reduction of 1 mmol/l after one year of cholesterol lowering treatment by statins results in a 23% reduction of major coronary events and a 21% reduction of major vascular events respectively (Cholesterol Treatment Trialists’ Collaborators, Lancet 2005;366:1267). The event-reducing effects of statins are now well-established on the long-term (Ford, N Engl J Med 2007; 357:1477). Moreover, a recent meta-analysis demonstrated the importance of intensive LDL-C lowering (Cannon, J Am Coll Cardiol 2006; 48:438) and recent trials using coronary intravenous ultrasound (IVUS) techniques have shown that LDL-C lowering is directly associated with coronary atheroma volume reduction (R2= 0.95, p<0.001).
Conversely, levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to CVD risk. In contrast to successful LDL-C lowering by statins, HDL-C rising therapies have not been successful to date. Recently, the ILLUMINATE trial, evaluating the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib, was terminated due to a significantly increased risk of mortality and morbidity in the atorvastatin/torcetrapib treatment arm (Barter, N Engl J Med 2007; 22;357(21):2109). Hence, intensive LDL-C lowering with statins remains the mainstay of CVD prevention. Total cholesterol (TC) and LDL-C levels below 5 and 3 mmol/l or 4.5 and 2.5 mmol/l respectively, depending on treatment setting, are currently recommended. In subjects with myocardial infarction and unstable angina, reducing TC and LDL-C levels below 4 and 2 mmol/l respectively, has been proven cost effective (EUROASPIRE).
Finally, it has recently been investigated whether statins are also beneficial in subjects with heart failure (HF) and in subjects with valve disease. In the CORONA trial, the effect of 10mg of rosuvastatin versus placebo on top of optimal HF treatment (diuretics, ACE inhibitors, ATII- receptor- and beta-blocker therapy) was evaluated in 5011 patients with chronic ischemic systolic heart failure. Rosuvastatin did not reduce the primary outcome (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) or the number of deaths from any cause, although the drug did reduce the number of cardiovascular hospitalizations. Rosuvastatin did not cause safety problems (Kjekshus, N Engl J Med 2007; 357 (22):2248). In the SEAS trial, the effect of 40mg simvastatin combined with 10mg ezetimibe or placebo was evaluated in 1873 patients with mild to moderate asymptomatic aortic stenosis. Simvastatin/ezetimibe combination therapy did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis when compared to simvastatin alone. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis (Rossebo, N Engl J Med 2008; 359(13):1343).

In summary, dyslipidemia remains the single most important cardiovascular risk factor and statins remain the cornerstone of CVD prevention. By lowering LDL-C levels, statins reduce all CVD endpoints, including fatal and non-fatal myocardial infarction, stroke and overall hospital admissions, without causing major adverse effects. These benefits have been demonstrated in subjects across all ages, in subjects with diabetes and in both primary and secondary prevention setting. Statins, however, do not improve heart failure.