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Maximising secondary prevention therapies in patients with coronary heart disease
  1. S Capewell,
  2. M O’Flaherty
  1. Division of Public Health, University of Liverpool, UK
  1. Dr S Capewell, Division of Public Health, Whelan Building, Quadrangle, University of Liverpool, L69 3GB, UK; m.oflaherty{at}

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Population-based primary prevention strategies are the only affordable solution for most developing countries. However, wealthier countries have the luxury of being able to support the complementary strategies of primary and secondary prevention. Ideally, almost all patients with coronary heart disease (CHD) can change their behaviour (smoking cessation, healthy diets and exercise-based rehabilitation) and receive secondary prevention medications (antiplatelet therapy, statins, ACE inhibitors and β-blockers, if there are no specific clinical contraindications).1

Secondary prevention drugs are important; they may explain about 10% of the fall in CHD death rates seen in the UK population between 1981 and 2000, much as in the USA between 1980 and 2000 and elsewhere.2 3 Furthermore, secondary prevention medicine is relatively cheap and cost effective.4

Recognising that uptake by 100% of eligible patients with CHD might be unrealistic, the UK CHD National Service Framework (NSF) in 1999 sensibly started with 80% targets. Yet even these remain challenging, given the disappointing service performance across Europe, quantified by two Euro ASPIRE studies.5 6

In this issue of Heart, DeWilde and colleagues describe their review of UK trends in CHD secondary prevention therapies between 1994 and 2005 using DIN, a UK GP prescribing database (see article on page 83).7 This was a large dataset covering 201 general practices “comparable to the UK norm”. Some data validation occurred but year-to-year repeatability was only 74% in men and 69% in women. This was not ideal, and may suggest a population in flux. Case ascertainment will inevitably be less than 100%. Thus the observation that the population-based prevalence of disease may have apparently increased slightly is problematic, particularly given the decreasing prevalence reported by the slightly more robust British Regional Heart Study.7 However, revascularisation rates undoubtedly did increase, consistent with many other studies.

Given that these DIN results are broadly consistent with earlier studies, what are the main messages?

Despite slow improvements, few patient groups hit the 80% target for secondary prevention drugs, and barely half were receiving desirable combinations.7 By 2005, 80% of men were taking a statin, 75% antiplatelet drugs and some 55% β-blockers or ACE inhibiters (in women, 70%, 75% and 50%, respectively). But only about 55% men and 45% women were receiving a three-drug combination, and only 26% men and 19% women four drugs. This did, however, represent substantial increases since 1994; the proportion of patients receiving no treatment decreased massively, from 43% to 5%. Medication rates were twice as high in patients surviving infarction or revascularisation as in patients with angina; this is disappointing, considering that their event rates are also high.8 Medication rates in elderly patients were just one-third of those of younger groups.7

The improving medication trends were gradual, with no sudden steps visible after the NSF in 2000. This is perhaps unsurprising given the inertia seen in large complex systems, such as the UK National Health Service. The new remuneration systems for general practitioners (Quality and Outcomes Framework (QOF)) may achieve some further improvements.

Although medication uptake rates were better than the ASPIRE studies of hospital-based patients, the NSF targets are still being missed. Furthermore, important inequalities persist, with substantial gradients disadvantaging older patients and women. These inequalities are particularly frustrating because the oldest patients have the highest event rates and would potentially benefit the most. Indeed, our group has suggested that consistently hitting the 80% target might result in some 20 000 fewer CHD deaths each year in the UK.9 Corresponding reductions in morbidity and hospital admissions might also be reasonably expected, along with decreasing demands for costly revascularisation procedures.9

Curiously, medication gradients were not seen across social groups. This conflicts with clinical experience, and with other studies examining social gradients and prescribing in CHD.1012 This anomaly raises the possibility of differential case ascertainment. In other words, because a CHD “iceberg of disease” may still exist, disproportionately more deprived patients with CHD might have failed to get onto the DIN registers. That concern merits further study, not least because of the higher case fatality likely in deprived groups.13

Further interesting questions remain. First, we still do not know how best to calculate the cumulative benefits of combination therapy in patients with cardiovascular disease. Common sense suggests that simply summing the relative mortality reductions is inappropriate. For instance, if combining aspirin, β-blocker, ACE inhibitor, statin and smoking cessation, adding 10%, 15%, 20%, 25% and 40%, respectively, together would exceed 100%, and yet we know that even our most compliant patients do not live forever. The current convention is therefore to use Mant and Hick’s cumulative relative risk (RR) approach where the total relative risk reduction (RRR)  =  1– (1−RR treatment A) × (1−RRR treatment B), etc.2 14 15 This appears plausible, and is acceptable to most clinical pharmacologists, but some more empirical data are still urgently required. The second question is, what is the true scale of the potential increase in life expectancy?. The median survival following a first myocardial infarction is barely 6 years.8 Thus even optimal treatment may generate surprisingly few additional life-years.4 Again, empirical data would be valuable.

Despite this yet unanswered questions, increasing prescribing rates of evidence-based therapies is a necessary and desirable objective. Furthermore, we still need to overcome many barriers to evidence-based decisions in everyday clinical practice.16

We must also remember that increasing prescribing rates is just part of the solution; encouraging patients to take their prescribed treatment is as important, because poor compliance is associated with substantial risk.17 Yet medical practice exists within a complex social environment. In reality, sustained long-term treatment usually follows a successful negotiation between patient and practitioner. Illness behaviour and wider social factors powerfully influence this process. For instance, despite having some knowledge of their condition patients with CHD may still not fully appreciate their risk of further events;18 they therefore may feel less involved in their own treatment. Furthermore, recent studies suggest that long-term treatment compliance might vary by symptom status or CHD severity; medication compliance in asymptomatic patients may be 50% or less.19 20

Doctors therefore face real frustrations, because asking patients with CHD to take three, four or five different treatments can mean handfuls of tablets every day; simplifying drug regimens is therefore a fundamental tool for improving compliance. Combination tablets such as the “polypill” offer substantial theoretical attractions.14 However, the history of pharmacology is littered with broken dreams. Both impoverished health service planners and sceptical clinicians may require convincing evidence of benefits from randomised control trials of the polypill focusing on patients with CHD, not just the current trials in disease-free subjects.


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  • Competing interests: None.

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