Richard M. Steingart, MD is chief, Cardiology Service, Memorial Sloan-Kettering Cancer Center

Practicing cardiologists often joke about putting “statins” in the drinking water to stem the epidemic of atherosclerotic cardiovascular disease, but curiously, I don’t believe that refers, even in jest, to a cocktail combination of drugs. On the other hand, the problems surrounding polypharmacy do come up frequently in management discussions, particularly in the treatment of elderly patients. Here, the discussion revolves around drugs needed to treat contemporaneous comorbidities, such as arthritis, hypertension, and diabetes. Cardiologists also discuss incremental drug therapies to control angina, stepwise pharmacologic management of heart failure, and combination therapy for the management of acute coronary syndromes. 

 in his careful analysis of the cost-utility of aspirin and statins, alone and in combination, for the primary prevention of coronary artery disease (CAD) events in men. Coronary artery disease events are defined as angina, stroke, myocardial infarction, and death from CAD. Coronary artery disease defined as only hard end points would be expected to yield somewhat different results. The authors report a potential conflict of interest, with consultancies, expert testimony, and grants received from Bayer and Pfizer, manufacturers of products analyzed in this article. 

 This article led me to review the American Heart Association guidelines for the primary prevention of cardiovascular disease.

 These guidelines set the goal of low-dose aspirin use for patients at “higher risk” for CAD, especially those with a 10-year risk > 10%. Cholesterol lowering is also recommended if the CAD risk is high and the low-density lipoprotein cholesterol level exceeds a threshold. The guidelines do not explicitly discuss the incremental cost utility of these interventions. This combined cost-utility analysis is the major conceptual advance contained in the article by Pignone and colleagues. 

 The authors employ a Markov model, which, according to Wikipedia has become a ubiquitous tool in bioinformatics since its introduction in the 1960s. Whether their model accurately reflects what would be discovered in a prospective controlled trial is, of course, at issue. Table 1 in Pignone and colleagues’ original article lists the many base-case estimates constructed,

 reminding the reader of the potentially incorrect assumptions inherent in the best theoretical analyses, including variables entered and those omitted. At least for those variables entered, sensitivity analyses were performed to show that the estimates of cost utility were robust enough to withstand major variability in base-case assumptions. 

 The authors acknowledge that although aspirin was both more effective and less costly than no therapy in the base case, the quality adjusted life years and money saved were both modest compared with no therapy. Benefits increase with the risk of CAD. They also note that errors in estimating the risk of hemorrhagic stroke due to aspirin, particularly at low baseline levels of CAD risk, could invalidate their model. Additional empirical research is needed, particularly in patients at low risk. The authors also acknowledge that they did not model a discontinuation rate for statins related to liver enzyme abnormalities. Such discontinuation would decrease the cost effectiveness of statins. In my experience, discontinuation resulting from subjective complaints of myalgia, particularly when statins are used for primary prevention, is a much larger issue. 

 In sum, this analytic model suggests that aspirin alone is efficacious and cost effective in men with an average level of risk for CAD. The addition of a statin is more cost effective as risk increases. Just imagine how powerful linked data from Medicare Parts A, B, and D could be in furthering such analyses! Right now, in part related to privacy concerns, drug and clinical data exist in their own isolated silos. 

Articles

Practicing cardiologists often joke about putting "statins" in the drinking water to stem the epidemic of atherosclerotic cardiovascular disease, but curiously, I don't believe that refers, even in jest, to a cocktail combination of drugs.

Aspirin and statins for prevention of coronary artery disease

Each municipality in      Finland is responsible for arranging health care for its inhabitants.

 Most have switched from a primary health care system to a family doctor system. Each family doctor is responsible for about 2000 patients. The aim is for a patient to be able to contact his or her doctor and to have treatment needs assessed within 3 working days. This system has proved very successful. Benefits of long-term treatment relationships include a reduced need for hospital examinations. This has helped to reduce health care costs.

 Health services are available to all citizens in Finland, regardless of their financial situation. Public health services are mainly financed from tax revenues—partly municipal tax, partly state tax. Finland spends less than 7% of its gross national product on health care. This is one of the lowest percentages among European Union member states. The public sector finances 76% of total health care expenditures, users of services finance 20%, and others finance 4%. The decline in public sector health care expenditures in recent years has led to increases in costs to households. 

 Private medical treatment supplements the care provided by municipalities and the state. Particularly in cities, many doctors, dentists, and physiotherapists offer private care. There are also a few small private hospitals. Only about 8% of Finnish doctors earn their living solely as private practitioners. However, about one third of doctors run a private practice in addition to working in a hospital or health center. Everyone in Finland is covered by obligatory sickness insurance, funded through taxes by the state, municipalities, employers, and the insured population. The sickness insurance scheme reimburses fees paid by patients to private doctors, costs of medicines prescribed, and transportation costs arising from the treatment of illness. By far, the greatest expenditure in relation to health insurance is compensation for sick leave and parental leave. 

 The life expectancy for individuals born today is 81 years for girls and 73 years for boys. The life expectancy of Finnish men is deteriorated by cardiovascular disease, excessive consumption of alcohol, and accidents. Cardiovascular mortality has declined in response to effective health and nutritional education in recent decades, but excessive blood cholesterol levels and obesity remain common in Finland. Smoking and drug abuse, however, are significantly less frequent in Finland than in Europe, on average. 

 among men and women in Finland. Their article is a remarkable contribution in that it is a study of a symptom and its consequences in an entire population. Their main point is that angina should not be considered a “soft diagnosis” in women because standardized mortality ratios (SMRs) for women and men with angina were similar. SMR is the ratio of observed to expected deaths, the latter being calculated from age, sex, and calendar year-specific coronary mortality rates from the total Finnish population. However, if one examines absolute death rates, they are very low for young women with angina, particularly “nitrate angina.” This, then, is a restatement of the problem of managing a low-prevalence, but potentially dangerous, disease (coronary heart disease) that most often presents in women as a rather nonspecific symptom (angina). 

 Although helpful from an epidemiologic perspective, SMRs are not of particular value to the clinician trying to sort through the meaning of the clinical presentation. For example, in the article, Figure 2 shows that SMRs for angina decline with increasing age, whereas in clinical practice, the positive predictive value and prognostic implications of angina increase dramatically with age. Certainly, the presence of diabetes should raise the index of suspicion that chest pain in a woman of any age is a manifestation of coronary heart disease. Test-positive angina can do the same. But to use those tests cost effectively, the clinician must incorporate patient age, sex, symptoms, and conventional risk factors into an estimate of pretest disease likelihood. Bayes’ theorem revisited. To conclude, Hemingway and colleagues should be congratulated for an excellent population study, as should the people of Finland for their health care delivery and reporting system. 

Each municipality in Finland is responsible for arranging health care for its inhabitants.