Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis

Summary

Background

Cardiovascular disease is the leading cause of death, with 80% of cases occurring in developing countries. We therefore aimed to establish whether use of evidence-based multidrug regimens for patients at high risk for cardiovascular disease would be cost-effective in low-income and middle-income countries.

Methods

We used a Markov model to do a cost-effectiveness analysis with two combination regimens. For primary prevention, we used aspirin, a calcium-channel blocker, an angiotensin-converting-enzyme inhibitor, and a statin, and assessed them in four groups with different thresholds of absolute risks for cardiovascular disease. For secondary prevention, we assessed the same combination of drugs in one group, but substituted a β blocker for the calcium-channel blocker. To compare strategies, we report incremental cost-effectiveness ratios (ICER), in US$ per quality-adjusted life-year (QALY).

Findings

We recorded that preventive strategies could result in a 2-year gain in life expectancy. Across six developing World Bank regions, primary prevention yielded ICERs of US$746–890/QALY gained for patients with a 10-year absolute risk of cardiovascular disease greater than 25%, and $1039–1221/QALY gained for those with an absolute risk greater than 5%. ICERs for secondary prevention ranged from $306/QALY to $388/QALY gained.

Interpretation

Regimens of aspirin, two blood-pressure drugs, and a statin could halve the risk of death from cardiovascular disease in high-risk patients. This approach is cost-effective according to WHO recommendations, and is robust across several estimates of drug efficacy and of treatment cost. Developing countries should encourage the use of these inexpensive drugs that are currently available for both primary and secondary prevention.

Introduction

Cardiovascular disease is responsible for about 30% of all deaths worldwide, with about 80% of total deaths occurring in developing countries.¹ Yet little global attention has been focused on the challenge of reducing this burden in developing countries.2, 3 This deficit is compounded by the fact that the resources to combat cardiovascular disease in these same countries are typically very scarce. Health-care expenditure per head in developing countries is about 2–3% of the amount spent on health care in developed countries.⁴ Thus, recommendations regarding the prevention of cardiovascular disease should account for the costs of such interventions as well as the best available evidence of efficacy.

Publications5, 6, 7 have suggested that the combination of several preventive treatments could cut more than half the occurrence of cardiovascular disease. Wald and Law⁵ specifically proposed a polypill, consisting of a statin, aspirin, a β blocker, an angiotensin-converting-enzyme inhibitor (ACEI), a thiazide, and folic acid. Although the notion of one formulation could ultimately prove beneficial, there are several reasons why the polypill as originally proposed would not work nowadays and why we should not delay in recommending a multidrug regimen that is currently known to work. First, trial results with clinical endpoints for the polypill do not yet exist, and could be several years away from validation. Second, randomised trial evidence on folate8, 9, 10, 11 shows no benefit for cardiovascular disease so far. Third, no data indicate the efficacy of any three added blood-pressure drugs given together. Finally, combination treatment does not require that the different drugs be combined in one pill. Although adherence could be improved if a polypill was used compared with drugs taken separately, this effect has not been proven. While these trials are in progress, individual components of potential multidrug prevention regimens are already available but underused in developing countries, resulting in millions of potential deaths that could be averted. For example, ACEIs and statins are used for secondary prevention by fewer than 20% and 10% of the eligible population, respectively,¹² and even less so for primary prevention. Thus current recommendations, especially for developing countries, should focus on drugs that are proven effective and are also cheap and available.

The best drugs for secondary prevention in patients with clinical ischaemic heart disease are aspirin, β blockers, ACEIs, and statins. Optimum treatment for primary prevention has had greater debate, especially with respect to antihypertensive drugs. Although the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)¹³ showed that thiazides were as effective as a calcium-channel blocker or ACEI, more than one drug was clearly needed to control blood pressure and the study was not designed to assess which combination was preferable. However, the results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA)¹⁴ showed that a calcium-channel blocker and an ACEI were more effective than than the traditionally proposed first-line drugs of thiazide and β blocker. Further, the addition of a statin in the lipid-lowering group of the same trial showed added benefit.¹⁵ The association of β blockers and diuretics with the development of diabetes in hypertension trials14, 16, 17, 18 makes this combination a less attractive choice for primary prevention.

The results of ACEI, CCB, or ACEI over β blockers for primary prevention19, 20 was assessed by the National Collaborating Centre for Chronic Conditions,²¹ leading to the British Hypertension Society²² to remove β blockers from the first three choices for hypertension. Thus, aspirin, CCB, an ACEI, and a statin should be recommended for primary prevention, which means that two different drug combinations might be needed for primary and secondary prevention. We note that all suitable protective components are now not patented in developing countries and are inexpensive.

Although treatment benefits could be widely applicable, costs and the ability to pay can vary greatly among developing countries. Hence, health-care decisions should be guided by local cost-effectiveness. Therefore, we investigated whether four generic drugs (aspirin, two anti-hypertensive drugs, and a statin) would be cost-effective in resource-poor settings for three groups: patients with cardiovascular disease, those without previous disease but with varying 10-year absolute risks of the disease, and those older than 55 years who would not need any additional risk factor assessment.