PURE: CV Drugs Underused in Poor Nations, Rural Populations

August 28, 2011

(Updated August 28, 2011) (Paris, France) — Gaps between affluent and underdeveloped nations and between city and rural populations are apparent in many ways, and among the most devastating may be in the penetration of proven medical therapy for secondary prevention of cardiovascular diseases, suggests a survey of 628 communities in 17 high-, middle-, and low-income countries [1].

"Effective preventive drugs for coronary heart disease and stroke are underused globally, with striking variation between countries at different stages of economic development," write the authors, led by Dr Salim Yusuf (McMaster University, Hamilton, ON), based on their findings from the Prospective Urban Rural Epidemiology (PURE) study.

"Even the use of accessible and inexpensive treatments such as aspirin . . . varied sevenfold between low-income and high-income countries," they write; statin use varied 20-fold. And even in the highest-income countries in the survey, only one-half to two-thirds of people with a history of MI or stroke were taking either aspirin or statins.

"For every group of countries classified by economic development, rates of drug use were consistently lower in rural than in urban settings." The analysis--which looked at the use of antiplatelets, beta blockers, ACE inhibitors or angiotensin receptor blockers (ARBs), statins, and other agents among persons with coronary heart disease or stroke--was published online today in the Lancet to coincide with its presentation by Yusuf here at the European Society of Cardiology (ESC) 2011 Congress.

These are the cheapest, the safest, and the most effective drugs. And yet we have a collective global failure.

In his formal presentation, Yusuf said the worldwide pattern of drug underuse "represents a colossal human tragedy that is easy to overcome, relatively speaking. Of everything in cardiology, these are the cheapest, the safest, and the most effective drugs. And yet we have a collective global failure."

Speaking with heartwire , Yusuf said the failure occurs at every level, from political and economic systems down to the care of individuals by physicians. Indeed, he notes, secondary prevention of CV disease would likely reach more people if nonphysician health workers had a larger role. Perhaps 90% of the people who should be receiving these drugs, he said, shouldn't actually have to see a doctor to get them.

Focus on the Well-Known Risk Factors

As the featured discussant after Yusuf's presentation, Dr Aldo Pietro Maggioni (Italian Association of Hospital Cardiologists Research Center, Firenze, Italy) pointed out that some of the variation in secondary-prevention drug use could be explained by international differences in extent of reimbursement, regardless of degree of national economic development.

Moreover, he said, "it is my firm opinion that a real improvement in global cardiovascular health could likely be obtained through preventive strategies focused on the well-known risk factors, including lifestyle changes."

Also useful, according to Maggioni, would be "sociopolitical strategies focused to increase the use of preventive drugs more than through the identification of new sophisticated predictive biomarkers or modest refinements of the pharmacological properties of existing classes of drugs."

In an editorial accompanying the Lancet report from Yusuf et al [2], Dr Anthony M Heagerty (University of Manchester, UK) notes there is a prevailing assumption that physicians will adapt their management strategies in response to overwhelming clinical-trial data, but "considering issues such as national prosperity and availability of healthcare, do doctors respond as expected?"

We in this room should delegate, give up the role of prevention to other people who can do the work just as well with much more limited training and much less cost.

The current analysis "provides a stark and alarming message," he writes. The shortfalls in wealthier countries are "disappointing," but a daunting 80% of patients surveyed in the low-income countries are taking none of the proven secondary-prevention medications.

In those countries, "Drug availability and access to healthcare will conspire to worsen the situation, together with the need for coordinated strategies to provide long-term preventive programs for diseases of the heart and circulation," according to Heagerty.

"Partnership with industry, as undertaken in the fight against HIV, could reap immediate and valuable rewards where cheap generic drugs are not available." The study from Yusuf et al, he writes, "suggests that strong action is needed. An epidemic of cardiovascular disease is just beginning in many countries that are ill-prepared for what is to come."

"High-Quality Data on a Modest Budget"

The survey, covering 2003 to 2009, encompassed 153 996 adults from urban and rural communities in countries categorized as high-income (Canada, Sweden, and United Arab Emirates), upper-middle-income (Argentina, Brazil, Chile, Malaysia, Poland, South Africa, and Turkey), lower-middle-income (China, Colombia, and Iran), and low-income (Bangladesh, India, Pakistan, and Zimbabwe). The specific countries were chosen with consideration of needs for long-term follow-up and "high-quality data with a modest budget."

Based on individual participant responses, 5650 people overall had experienced a CHD event a median of five years previously, and 2292 had had a stroke a median of four years earlier.

Cardiovascular Drug Use for Secondary Prevention Among Patients With CHD or Stroke, by Nation Economic Status

CV drug category High-income (%) Upper-middle income (%) Lower-middle income (%) Low-income (%) Overall
Antiplatelets 62.0 24.6 21.9 8.8 25.3
Beta blockers 40.0 25.4 10.2 9.7 17.4
ACE inhibitors or ARBs 49.8 30.0 11.1 5.2 19.5
BP-lowering agents 73.8 48.4 37.4 19.2 41.8
Statins 66.5 17.6 4.3 3.3 14.6

All decreasing trends from higher- to lower-income, p<0.0001

Consistently, secondary-prevention CV drug use was more prevalent among patients in urban than in rural communities, with the gaps most pronounced in the lowest-income countries.

Cardiovascular Drug Use for Secondary Prevention Among Patients With CHD or Stroke, Urban vs Rural Populations Across All Surveyed Countries

CV drug category Urban (%) Rural (%)
Antiplatelets 27.7 21.5
Beta blockers 20.3 13.1
ACE inhibitors or ARBs 22.3 15.4
BP-lowering agents 47.1 33.7
Statins 17.2 10.6

All differences urban vs rural, p<0.001

It was also found that patients <60 years of age were significantly less likely to be on one of the drugs than were older patients, and female patients significantly less likely than male patients. However, according to Yusuf et al, "The economic status of the country accounted for about two-thirds of the variations in drug use, whereas only a third was accounted for by individual factors," including age, sex, education, smoking status, body-mass index, and whether the patient had hypertension or diabetes.

That, Yusuf said in his presentation, "means that the biggest flaw is the fact that most systems in the world do not have an organized approach to secondary prevention." It also means that efforts to improve the penetration of secondary-prevention CV drugs should focus on "national policies and structured health systems," he said.

"This large global gap in use of proven, inexpensive, and safe strategies can be readily dealt with if we have the political will" to redefine the role of physicians in this setting, in that "delivery of simple preventive strategies should be done by nonphysicians," Yusuf said.

"We in this room should delegate, give up the role of prevention to other people who can do the work just as well with much more limited training and much less cost."

The report discloses that funding for PURE comes from independent, public sources around the world (details are in the report) as well as industry, including grants from "several pharmaceutical companies, [with] major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline, and additional contributions from Novartis and King Pharma," as well as the Unilever Health Institute in Brazil and the South African Sugar Association. The study authors declare they have no conflicts of interest. Heagerty discloses that he has consulted or received fees for speaking from Servier, Merck Serono, Novartis, and Daiichi-Sankyo. Maggioni had no disclosures.

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