Persistence with antihypertensive medication: Australia-wide experience, 2004–2006

Persistence with long-term medication in patients with hypertension or dyslipidaemia is generally unsatisfactory outside the context of controlled trials.1-7 Of 32 000 Australian patients initiated on a lipid-modifying drug in a single month of 1999, 30% had discontinued therapy within 6 months.5 European and North American studies have estimated that around 50% of all patients using antihypertensive (AHT) drugs had discontinued within 6 months to 4 years.3,8,9

We analysed Medicare Australia Pharmaceutical Benefits Scheme claims for AHT drugs over the period 2004–2006, with special reference to the most prominent classes of AHT drugs currently used in Australia, namely angiotensin II receptor antagonists (A2RAs), angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs). Using these data as a broad surrogate for persistence with medication, we derived a picture of persistence and adherence in Australian patients prescribed these drugs.

Information on 48 690 patients prescribed AHT drug therapy was obtained. Fifty-six per cent were females. The age distribution was as follows: 13% < 50 years, 38% 50–69 years, 49% ≥ 70 years. General practitioners issued 86% of prescriptions, the balance being provided by specialists. The proportions of the respective drug classes prescribed were: A2RAs 27%, A2RA+s 6%, ACEIs 52%, ACEI+s 4%, CCBs 19% (the total of these exceeded 100%, as some patients were initiated on multiple drugs). We grouped the findings into three classes: A2RAs (including A2RA+s), ACEIs (including ACEI+s) and CCBs.

Persistence curves for the three drug classes are shown in Box 1, and key derived statistics are summarised in Box 2. Apparent persistence was unsatisfactory for all drug classes, but poor persistence was notably higher in patients prescribed CCB therapy. Compared with patients taking A2RAs, 57% more patients who began on CCBs had discontinued therapy by the end of the period studied (log-rank P < 0.001). There were no major differences in persistence patterns between patients taking A2RAs and ACEIs. Poor persistence in this analysis was defined as complete cessation of all AHT drugs.

Key persistence statistics for individual drugs are summarised in Box 3 (this analysis is specific to the drug prescribed and takes no account of switching to an alternative drug). Within the A2RA class, patients commencing on candesartan or telmisartan showed the best apparent persistence (by a margin of 10%–20%); within the ACEI class, patients prescribed perindopril showed the best apparent persistence (about 25% better than other class members); and within the CCB class, patients prescribed lercanidipine showed the best apparent persistence (at least 25% better than other class members). Median MPRs (based on the assumption that patients are prescribed, and take, one dose per day) were close to 100%, with the notable exception of captopril (72%).

Key persistence statistics, by age and sex, are shown in Box 4. Poor persistence in this analysis was defined as complete cessation of all AHT drugs. The best apparent persistence data were observed in the age group 60–69 years, the poorest in patients aged under 40 years. There were no major differences between male and female patients, or according to prescriber (GP or specialist prescriber) (data not shown).

Our results confirm that long-term persistence with AHT drugs (44% of patients) is still relatively unsatisfactory. On the other hand, patients who continue with therapy seem to adhere to the treatment regimen reasonably well. Our findings are consistent with the observation that hypertension worldwide is poorly controlled in many patients,7 despite the availability of safe and effective drugs to treat the condition.4,7,10

Persistence analyses were recently published by the Australian Institute of Health and Welfare (AIHW).11 Persistence was examined only in patients who had filled a minimum of two prescriptions (in contrast with our study, which had no such restriction). Given the high proportion of patients in our study who failed to fill a second prescription, the AIHW analysis would have produced a more optimistic outcome than ours. For example, persistence at 24 months on A2RAs and ACEIs was about 75%–77% in the AIHW analysis, compared with around 50% in our study. The AIHW report did present directly comparable data on the proportions of patients using A2RAs and ACEIs who failed to collect a second prescription (15% and 18%, respectively) — proportions that were in close agreement with our own findings.

Our approach had certain limitations: we did not know patients’ medical histories; some patients may have used AHT medications for indications other than hypertension; and only concession card holders were studied (nevertheless, they represent about 65% of Australian patients using these medications — a highly meaningful proportion). Patients without concession cards are likely to be younger, to make higher copayments and to be poorer compliers (as suggested in Box 4). We have also made the broad assumption that patients in our study were new to AHT therapy. It is possible that some patients were actually returning to therapy after previous cessation.

Adverse events associated with AHT drugs may contribute to poor persistence with therapy.3 In one study, more than 40% of patients changed their AHT therapy because of adverse events.12 In our study, we observed broadly similar apparent persistence whether patients were initiated on A2RAs or ACEIs, yet there was poorer persistence in those initiated on CCBs. This pattern, reported previously,3,4,11,13 is probably related to the propensity of some CCBs to induce peripheral oedema.14 Brand price premiums attached to CCBs could also affect patients’ willingness to persist in using them. It is a therapeutic challenge that the poorest persistence was in the youngest and oldest age groups, but some of the oldest patients may have died during the time period studied.

Does poor persistence affect clinical outcomes? Analysis of cardiovascular disease outcomes in the Second Australian National Blood Pressure Study showed a 20%–23% higher event rate in patients reporting poor compliance with medication.15 A North American study of patients with diabetes and coronary disease reported 40% lower mortality in patients complying with “cardioprotective” medications, while those poorly compliant had the same mortality rate as their peers not using medications.16

What can be done to improve persistence? Better patient education, as well as the availability of drugs with fewer side effects, more convenient once-daily dosing schedules and combination products, may encourage greater compliance. Ultimately, better persistence and better control of hypertension will rest on a partnership between health professionals and individual patients. If we cannot achieve better persistence, we will be wasting valuable resources, and an opportunity for cardiovascular disease prevention will be lost.

1 Persistence curves for the three main classes of antihypertensive drugs initiated in Australia, January 2004 to September 2006

* A2RA = angiotensin II receptor antagonist. ACEI = angiotensin-converting enzyme inhibitor. CCB = calcium channel blocker.