Letter by Superko and King Regarding Article, “Lipid Treatment Assessment Project 2: A Multinational Survey to Evaluate the Proportion of Patients Achieving Low-Density Lipoprotein Cholesterol Goals”
To the Editor:
The article by Waters et al1 on the improvement in blood lipid values during the past 10 years is encouraging and certainly in large part the result of national and international cholesterol education programs. Waters et al report that the percentage of surveyed individuals who reached their low-density lipoprotein cholesterol(LDL-C) goal improved from 38% to 73%. Although this result is encouraging, the LDL-C–centric vision fails to give proper attention to the fact that many individuals with reduced LDL-C continue to experience cardiovascular events.2 For example, in the West of Scotland study, a relative risk reduction of 31% was reported, which equated to an absolute risk reduction of 2.4%.3 Forty-six patients required treatment to prevent 1 cardiovascular event, and in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a 16% relative risk reduction and a 3.9% absolute risk reduction were observed for treatment with 80 mg/day atorvastatin versus 40 mg/day pravastatin.4 Twenty-six patients required treatment to prevent 1 additional cardiovascular event.
Recent advances in the field of genetics allow the identification of a large fraction of the population that derives the majority of clinical event reduction benefit from statin therapy and event reduction that is independent of LDL-C and high-sensitivity c-reactive protein reduction.5,6 Such knowledge would allow physicians to concentrate statin therapy and statin compliance efforts in those patients who derive the most benefit (eg, KIF6 carriers) and identify another group of patients (eg, KIF6 noncarriers) who may benefit from investigation of non-LDL-C–related causes of atherosclerosis. For example, in the West of Scotland study and PROVEIT examples, KIF6 719Arg carriers treated with pravastatin in the West of Scotland study, exhibited a relative risk reduction of 50%, compared with 9% in the noncarriers. The absolute risk reduction was 5.5% in the KIF6 carriers compared with 0.1% in the noncarriers, and the number needed to treat was 18 in the KIF6 carriers and >100 in the noncarriers. In PROVEIT, treatment of KIF6 719 Arg carriers with atorvastatin (80 mg/day) versus pravastatin (40 mg/day) resulted in a 41% relative risk reduction, compared with a 6% relative risk reduction in the noncarriers. The absolute risk reduction was 10% in carriers, compared with 0.8% in noncarriers, and 10 patients in the KIF6 719Arg carrier group required treatment to prevent 1 event, compared with 125 in the noncarriers.
Achieving consensus guideline goals is a laudable accomplishment, but many patients with lower LDL-C continue to experience cardiovascular events. To dramatically reduce cardiovascular events, a more productive goal would be to differentiate patient subpopulations that benefit substantially from statin therapy and those who benefit significantly less.
Dr Gotto’s accompanying editorial7 makes the point that there is still a considerable gap in the treatment of patients at highest risk for cardiovascular events. This gap, thought to be explained mainly by LDL-C levels, may have more to do with genetics than previously thought. Genetic knowledge could allow physicians to make better therapeutic decisions for their patients.
Dr Superko is Chief of Medical Affairs at Celera, a genetic discovery company. Dr King serves as an academic consultant for Celera.
Waters DD, Brotons C, Chiang CW, Ferrières J, Foody J, Jukema JW, Santos RD, Verdejo J, Messig M, McPherson R, Seung KB, Tarasenko L, for the Lipid Treatment Assessment Project 2 Investigators. Lipid Treatment Assessment Project 2. A multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation. 2009; 120: 28–34.
Superko HR, King S III. Lipid management to reduce cardiovascular risk: a new strategy is required. Circulation. 2008; 117: 560–568.
Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM, Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004; 350: 1495–1504.
Iakoubova OA, Sabatine MS, Rowland CM, Tong CH, Catanese JJ, Ranade K, Simonsen KL, Kirchgessner TG, Cannon CP, Devlin JJ, Braunwald E. Polymorphism in KIF6 gene and benefit from statins after acute coronary syndromes: results from the PROVE IT-TIMI 22 study. J Am Coll Cardiol. 2008; 51: 449–455.
Iakoubova OA, Tong CH, Rowland CM, Kirchgessner TG, Young BA, Arellano AR, Shiffman D, Sabatine MS, Campos H, Packard CJ, Pfeffer MA, White TJ, Braunwald E, Shepherd J, Devlin JJ, Sacks FM. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J Am Coll Cardiol. 2008; 51: 435–443.
Gotto AM. Improving lipid goal attainment: is it enough? Circulation. 2009; 120: 3–5.