READERS’
COMMENTS
Economic Evaluation Cholesterol Lowering
of
I read the study “An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction” by Hay et al’ in the April 15 issue. One comment seems warranted. There is much data demonstrating that reducing high serum cholesterol levels is beneficial in decreasing the risk of coronary artery disease and its complications. The mortality of coronary artery disease decreases as we11.2-4 However, most importantly, there is little evidence of a decrease in total mortality attributable to reduced cholesterol,4,5 which is possibly due to the compensatory increase in mortality induced by other factors.2-4 As the authors state: “Better information on the outcome efficacy of lovastatin and other cholesterol reduction interventions is needed to establish firm guidelines for efficient allocations of health care resources in reducing coronary artery disease risk.” Wouldn’t it also be needed, in an otherwise excellent work like this, when calculating the cost per lifeyear saved? Juhani Partanen,
MD
Helsinki, Finland 10 June 1991 1. Hay JH, Wittels EH, Gotto AM Jr. An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction. Am J Cardiol 1991;67: 789-796. 2. Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br Med J 1990; 301:309-314. 3. Rossouw JE, Lewis B, Rifkind BM. The value of lowering cholesterol after Letters (from the United States) concerning a particular article in the Journal must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 doublespaced typewritten pages. Two copies must be submitted.
1120
THE AMERICAN
JOURNAL
myocardial infarction. N Engl J &fed 1990;323:1112-1119. 4. Holme I. An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. Circulation 1990; 82:1916-1924. 5. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W, and the Coronary Drug Project Research Group. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Co11 Cardiol 1986;8:1245-1255.
REPLY: Partanen raises valid considerations regarding the risks and benefits of lovastatin therapy and other cholesterol interventions. As we stated, our economic evaluation of lovastatin was performed in the context of “. . . what is currently known about the clinical, economic and safety profiles for lovastatin.“’ We consider such an evaluation to be justified by the fact that lovastatin and many other cholesterol interventions are being utilized today by millions of people worldwide. Rational allocation of increasingly strained health care resources imposes ever stricter standards of economic evaluation on all health care technologies. As better data become available, the accuracy of clinical and economic health care decisions will also be enhanced. Although Partanen is correct that the effect on all-cause mortality attributable to cholesterol reduction interventions has not been established with precision, there is evidence of significant reductions in total mortality associated with cholesterol reduction from a variety of epidemiologic studies and several cholesterol intervention trials with longer term followup.2l3 The Coronary Drug Project, Oslo Diet and Antismoking Trial, and the Stockholm Ischemic Heart Disease Study all showed reductions in total mortality, but also demonstrated the need for observing large numbers of patients for many years be-
OF CARDIOLOGY
VOLUME
68
OCTOBER
15,
1991
fore significant differences could be observed between patients undergoing treatment and control subjects.2 Much of the controversy surrounding the lack of association between cholesterol reduction and total mortality results from a misreading of such shorter term studies as the LRC-CPPT and the Helsinki Heart Study. Although these studies clearly demonstrate the clinical benefits of lipid modification, because of financial and time constraints they were not designed with the requisite statistical power to address the issue of all-cause mortality. Some studies have inaccurately concluded that a lack of mortality reduction benefits from cholesterol intervention studies that were neither designed nor expected to produce a test of such outcome differences. While coronary artery disease remains the leading fatal disease in the United States and many other industrialized nations, we take some consolation from the observation that even among those at relatively high risk for this disease, death is neither common nor immediate. Joel W. Hay, MD
Stanford, California Eikbn
Ha
witted,
MD
Antonio M. Gotto, MD, DPM
Houston, Texas 1 July 1991 1. Hay JW, Wittels EH, Gotto AM. An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction. Am J Cardiol 1991;67:
789-796. 2. Gotto AM, LaRosa JC, Hunninghake D, Grundy SM, Wilson PW, Clarkson TB, Hay JW. The cholesterol facts: a summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. Circulation 1990;8 1:172 l1733. 3. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W, and the Coronary Drug Project Research Group. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coil Cardiol 1986;8:1245-1255.
COMMENTS
Economic Evaluation Cholesterol Lowering
of
I read the study “An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction” by Hay et al’ in the April 15 issue. One comment seems warranted. There is much data demonstrating that reducing high serum cholesterol levels is beneficial in decreasing the risk of coronary artery disease and its complications. The mortality of coronary artery disease decreases as we11.2-4 However, most importantly, there is little evidence of a decrease in total mortality attributable to reduced cholesterol,4,5 which is possibly due to the compensatory increase in mortality induced by other factors.2-4 As the authors state: “Better information on the outcome efficacy of lovastatin and other cholesterol reduction interventions is needed to establish firm guidelines for efficient allocations of health care resources in reducing coronary artery disease risk.” Wouldn’t it also be needed, in an otherwise excellent work like this, when calculating the cost per lifeyear saved? Juhani Partanen,
MD
Helsinki, Finland 10 June 1991 1. Hay JH, Wittels EH, Gotto AM Jr. An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction. Am J Cardiol 1991;67: 789-796. 2. Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br Med J 1990; 301:309-314. 3. Rossouw JE, Lewis B, Rifkind BM. The value of lowering cholesterol after Letters (from the United States) concerning a particular article in the Journal must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 doublespaced typewritten pages. Two copies must be submitted.
1120
THE AMERICAN
JOURNAL
myocardial infarction. N Engl J &fed 1990;323:1112-1119. 4. Holme I. An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. Circulation 1990; 82:1916-1924. 5. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W, and the Coronary Drug Project Research Group. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Co11 Cardiol 1986;8:1245-1255.
REPLY: Partanen raises valid considerations regarding the risks and benefits of lovastatin therapy and other cholesterol interventions. As we stated, our economic evaluation of lovastatin was performed in the context of “. . . what is currently known about the clinical, economic and safety profiles for lovastatin.“’ We consider such an evaluation to be justified by the fact that lovastatin and many other cholesterol interventions are being utilized today by millions of people worldwide. Rational allocation of increasingly strained health care resources imposes ever stricter standards of economic evaluation on all health care technologies. As better data become available, the accuracy of clinical and economic health care decisions will also be enhanced. Although Partanen is correct that the effect on all-cause mortality attributable to cholesterol reduction interventions has not been established with precision, there is evidence of significant reductions in total mortality associated with cholesterol reduction from a variety of epidemiologic studies and several cholesterol intervention trials with longer term followup.2l3 The Coronary Drug Project, Oslo Diet and Antismoking Trial, and the Stockholm Ischemic Heart Disease Study all showed reductions in total mortality, but also demonstrated the need for observing large numbers of patients for many years be-
OF CARDIOLOGY
VOLUME
68
OCTOBER
15,
1991
fore significant differences could be observed between patients undergoing treatment and control subjects.2 Much of the controversy surrounding the lack of association between cholesterol reduction and total mortality results from a misreading of such shorter term studies as the LRC-CPPT and the Helsinki Heart Study. Although these studies clearly demonstrate the clinical benefits of lipid modification, because of financial and time constraints they were not designed with the requisite statistical power to address the issue of all-cause mortality. Some studies have inaccurately concluded that a lack of mortality reduction benefits from cholesterol intervention studies that were neither designed nor expected to produce a test of such outcome differences. While coronary artery disease remains the leading fatal disease in the United States and many other industrialized nations, we take some consolation from the observation that even among those at relatively high risk for this disease, death is neither common nor immediate. Joel W. Hay, MD
Stanford, California Eikbn
Ha
witted,
MD
Antonio M. Gotto, MD, DPM
Houston, Texas 1 July 1991 1. Hay JW, Wittels EH, Gotto AM. An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction. Am J Cardiol 1991;67:
789-796. 2. Gotto AM, LaRosa JC, Hunninghake D, Grundy SM, Wilson PW, Clarkson TB, Hay JW. The cholesterol facts: a summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. Circulation 1990;8 1:172 l1733. 3. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W, and the Coronary Drug Project Research Group. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coil Cardiol 1986;8:1245-1255.
