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ONTARGET: Medication adherence and outcomes in high-risk cardiovascular patients in the ONTARGET trial

Cardiovascular Pharmacology and Pharmacotherapy

Presenter | see Discussant report

Michael Bohm (Germany)

Presentation webcast

Presentation slides

List of Authors:


Discussant | see Presenter abstract

Luigi Tavazzi (Italy)

Presentation webcast

Presentation slides



Non adherence to prescribed medications is reported in all chronic diseases including very symptomatic or fatal diseases, such as asthma, tuberculosis, epilepsy, leprosy and all cardiovascular diseases. In the real world no more than 50% of patients adhere to long-term therapy.

Individuals with cardiovascular (CV) diseases who do not adhere to prescribed medications have increased risk for CV outcomes. A question rises whether this occurs because non adherers cannot benefit from the treatment effect, or non-adherence is an indicator of worse outcome itself, unrelated to the treatment.

The effects of non-adherence are difficult to disentangle. Two ways have been pursued:
1) analysis of “placebo populations” in randomized controlled trials, and 2) analyses of populations of “neutral” randomized controlled studies, that can be pooled for analyses.

The placebo populations were analyzed by comparing adherers vs non adherers to placebo. In several clinical trials, including Coronary Drug Project (CDP), Beta Blocker in Heart Attack trial and CHARM programme, adherence to placebo was associated with a lower risk of death. In CHARM the Hazard Ratio for death was 0.66 (95%CI 0,55 – 0,81) for patients adherent to candesartan as compared to non adherers, in the placebo group the hazard ratio for death of adherers was 0.64 (95% CI 0.53 – 0.78) with respect to non adherers to placebo.

The effects of adherence to placebo have also been tested in the ONTARGET study, a large randomized controlled trial with neutral results. The resulting data are reported in this meeting. The trial evaluated patients above 55 years with high CV risk and showed similar treatment effects between the AT1-antagonist telmisartan and the ACE-inhibitor ramipril but the combination was not superior to either agent used alone. Since there were no differences related to treatment, non-adherence to study medication was evaluated in the total study population.

Results of these analyses showed that patients non-adherent to study therapies showed several characteristic traits, and had higher event rates.. The increase in events occurred rapidly after stopping and events themselves led to higher non-adherence rates subsequently. So the patients entered a vicious cycle exposing them to a higher risk of further CV outcomes.

These findings may suggest either that stopping whatever RA system modulator may worse outcome (but about 60% of non adherers to the study drug took an open label RA system modulator after stopping the study drug) or that non-adherence is a marker of poor outcome in itself. So this study does not answer such critical question. However the finding that in several RCTs adherence to even placebo was strongly related to outcome suggests that adherent behaviour “itself” is associated with outcome. This is related in part to a poorer health profile of non-adherers. In part adherence to placebo is a surrogate for healthier behaviours, better self-management, adherence to recommended drugs, compliance to behaviours that favourably affect outcome. The need to improve adherent behaviour is obvious.


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Clinical Trial Update I - Drug treatment

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.