| Author | White HD. |
| Title | Adherence and outcomes: it's more than taking the pills. |
| Full source | Editorial - Lancet. 2005 Dec 10;366(9502):1989-91 |
| Text |
In
today's Lancet, Bradi Granger and colleagues1 report the findings of the
CHARM trials which show that high adherence, even if to placebo, was associated
with a 35% lower mortality than low adherence in patients with congestive
heart failure. Outcomes, including decreased admissions to hospital for
heart failure, were better in patients randomised to receive placebo who
adhered to treatment (took their study medications >80% of the time)
than in patients randomised to receive candesartan who did not have high
adherence (took their study medications <=80% of the time). Overall,
the CHARM patients randomised to receive candesartan in an adjusted analysis
had a 10% lower relative mortality than patients randomised to receive
placebo (p=0.032). Thus high adherence to placebo had a 3.5 times greater
effect on reducing mortality than the overall effect of candesartan. This
is not the first time that high adherence to placebo in patients with
heart disease has been associated with improved survival (eg, in three
previous trials, one of blockers in acute myocardial infarction,2 one
of cholesterol-lowering with niacin after myocardial infarction,3 and
one of amiodarone in patients with frequent ectopic beats after myocardial
infarction.4 Patients who are more unwell might not adhere to treatment,
but disease severity has not explained the association between adherence
to placebo and lower risk of mortality. The CHARM investigators found
no relation between adherence and ejection fraction or New York Heart
Association classification. Unique aspects of CHARM include the large
study population (nearly 7600) with symptomatic congestive heart failure
and receiving high rates of contemporary treatments for heart failure,
the 38-month follow-up, and the time-dependent analysis of events and
adherence. In CHARM, patients with high adherence were more likely to
be men and on blockers or diuretics, less likely to smoke, and to have
more comorbidities. In clinical trials, adherence is usually high because
of the frequent follow-up, the availability of free drugs and care, and
patients' selection. In CHARM, adherence was assessed by clinicians' estimates
and pill counts. 86% of patients took more than 80% of their medications.
Discontinuation rates other than for adverse events were similar in both
the candesartan and placebo groups. Without a direct measure of adherence-such
as blood levels-it is possible that adherence was overestimated,5 but
if more accurate assessments were made, the findings relating better outcomes
to better adherence would be expected to be stronger. The reasons that
adherence may result in lower mortality, even if the treatment is a placebo,
might relate to the same reasons that taking placebo works and to expectations
and belief that a therapy will work.6 The results of CHARM suggest that
adherence to the study drug is a marker for adherence to other effective
treat-ments or a surrogate for healthier behaviours that result in better
outcomes. Several factors that could affect outcomes were not measured,
including participation in cardiac rehabilitation programmes and management
of weight, diabetes, blood lipids, and blood pressure. Lifestyle approaches
such as increased physical activity,7 which could reduce obesity, hypertension,
dyslipidaemia, and insulin resistance, a cardioprotective diet, not smoking,
and moderate alcohol intake might also be associated with major reductions
in mortality.8 In clinical practice, patients with chronic asymptomatic
conditions such as dyslipidaemia or hypertension often take less than
half of their prescribed medications.9 Patients with heart failure take
only 70% of their medications.10 It is estimated that 64% of hospital
readmissions of patients with heart failure are caused by non-adherence.11
Patients with heart failure also have high rates of non-adherence for
advice about diet, sodium intake, and fluid restriction, daily weighing,
and daily exercise.12 Patients may also delay seeking medical advice despite
having been advised to do so if they have increasing shortness of breath,
fatigue, weight gain, or increased oedema.13 Non-adherence to advice about
limiting alcohol intake is also associated with readmissions for heart
failure.14 Several other factors are associated with poor adher-ence,
including age, socioeconomic status (education, income, occupation, and
population density), complexity of regimens, and social support and participation.15
The relation between adherence and social activities might indicate higher
motivation to adhere to treatment in those who are more engaged in enjoyable
activities.4 Adherence is also strongly influenced by the community where
patients live, how health providers practise, and the type of medical
practice. A retrospective study of 8406 patients to assess adherence with
starting concomitant antihypertensives and lipid-lowering therapies within
3 months found that at 6 months, only 36% of patients filed prescriptions
to request at least 80% of their prescribed medication. Patients were
more compliant if they began both therapies together.16 This finding could
have implications for the management of patients with heart failure because
there are now multiple therapies that have been shown to improve mortality,
and suggests that therapies such as angiotensin-converting-enzyme inhibitors,
blockers, and aldosterone antagonists should be started as closely together
as possible. Adherence is a complex behavioural process and should be
thought of as a combination of behaviours rather than one particular type
of behaviour.17 For example, reasons for non-adherence to regular physical
activity might be different from reasons for non-adherence to medications.
Several methods can improve adherence, including patient's and family
education, improved dosing schedules, and improved communication between
patients and doctors. Specialist heart-failure nurses can also make a
major difference.18 Several quality-improvement initiatives have been
developed to change physicians' behaviour to improve patients' adherence.17
New techniques, such as cell-phone reminders, medication kits with paging
systems, and electronic reminders are being evaluated. An updated Cochrane
review found that less than half of interventions tested in randomised
trials improved adherence, and less than a third improved outcomes. Effective
interventions were usually complex, involving combinations of several
interventions. The interventions did not have sustained benefits beyond
6 months. It is not known which component of these combined inter-ventions
is effective.19 Integrating the patient's perspective into treatment plans
with agreement that the treatment is more helpful than harmful may be
the most practical way to increase adherence.20 Poor adherence is common
in congestive heart failure, and results in poor outcomes and increased
costs. If adherence is improved, efficacy will be improved and treatment
will be more cost effective. However, the frequency of adverse events
may also increase and the risk-benefit ratio may be different than in
trials. Novel ways to improve adherence to both pharmaco-logical and lifestyle
measures must be developed, evaluated, and widely applied, so that patients
can reap the full benefits of the remarkable advances made in the management
of congestive heart failure. |