Long-term Survival after a Heart Attack

Summarized by Robert W. Griffith, MD
February 19, 2007

Summary

Adherence to medication with statins, and to a lesser extent, with beta-blockers, is linked to a reduced mortality during the 3-4 years following an infarct.

Introduction

We have summarized previously the importance of adherence to doctors' recommendations on medication use after a severe cardiac event (see first link below). A new study illustrates this. Data on the long-term survival of over 30,000 heart attack victims in Canada have been analyzed by the National Institute of Public Heath in Denmark. The findings in this study, however, provide valuable information for all countries, including the USA, where adherence to prescribed medications is not particularly good. Not only is the role of adherence evaluated, but also the value of adherence to particular types of medication is assessed. Here's a summary of the study that's published in the Journal of the American Medical Association.

What was done

The Ontario Myocardial Infarction Database collects health information, including medication history, on people in the Ontario area who have had a heart attack. The investigators selected for their study those patients aged 66 and over who had survived for at least 15 months after their hospitalization, covering the period 1999 to 2003.

The 30,000-plus patients were classified according to three types of drugs they were prescribed - statins, beta-blockers, and calcium-channel blockers. The first two are recommended as being able to help prevent a second heart attack, while the third (calcium-channel blockers) hasn't been demonstrated to have this effect, and served as a 'control'.

Adherence to a medication regimen (sometimes called compliance) is defined as the extent to which patients take their drugs as prescribed by their physician. It's usually reported as the percentage of the prescribed doses of a medication actually taken over a given period. In this study three categories of adherence were used - high (proportion of days covered more than 80%), intermediate (proportion of days covered 40% - 79%), and low (proportion of days covered less than 40%).

The average follow-up time was 2.4 years. Percentage survival curves (Kaplan-Meier curves) were constructed for a 4-year follow-up period.

What was found

The average 1-year adherence rate for all three drugs was high (~80%), with 88% still taking statins at one year. Over the 2.4 years' observation period, 13%, 20%, and 34% of patients taking statins, beta-blockers, and calcium-channel blockers, respectively, permanently discontinued their medication at some point.

The hazards ratios (HRs) for mortality based on the adherence at one year (high, medium, or low), with "high" adherence set as 1.0, are given in the table:

Adherence level at one year	Calcium-channel blockers	Beta-blockers	Statins
High	1.0	1.0	1.0
Medium	1.07	1.01	1.12*
Low	1.03	1.13*	1.25*

* statistically significant difference from "high" value 1.0

This means that, in the statins users, the risk of mortality was greatest for low adherers and least for high adherers. The findings were similar for beta-blockers, but less pronounced. There was no link between mortality and adherence to medication for those taking calcium-channel blockers.

Looking at the data another way, it was shown that mortality during the follow-up period for statin users was 24% for low adherence, 20% for intermediate adherence, and 16% for high adherence to medication. Beta-blocker users had similar but less pronounced findings. And there was no link between mortality and degree of adherence to calcium-channel blockers.

An analysis of the results separated according to the severity of the mortality risk for each patient was done. Recognized predictors of mortality (the Ontario AMI 30-day mortality prediction rule)¹ were used to classify the participants into three groups - low, medium, and high mortality risk. The analyses of these subgroups showed the same trends for adherence-linked mortality for the statin and beta-blocker users.

Comment

Previous studies of the advantages of adherence to cardiovascular medications have implied that the actual benefits may be due to an improved lifestyle in so-called "healthy adherers". This is based on an unexpected effect called "placebo adherence"; in this, participants in a placebo group in a clinical trial who demonstrated high adherence to taking their prescribed placebo had a lower mortality than low-placebo adherers.² The fact that the adherence benefits in the present study were different with the different drugs shows that the benefits were actually due to the drugs, rather than a lifestyle change.

From a practical viewpoint, this study shows that the protective effect of statins and, to a lesser extent, that of beta-blockers may be diminished by poor adherence to medication. Even if your cholesterol is within normal limits, that's not a reason to stop taking a statin; its cholesterol-lowering action is distinct from its cardioprotective effect (see second link below).

Source

• Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JN. Rasmussen, A. Chong , DA. Alter , JAMA, 2007, vol. 297, pp. 177--186

Footnotes
1. Development and validation of the Ontario acute myocardial infarction mortality prediction rules. JV. Tu, PC. Austin, R. Wallid ,  et al., J Am Coll Cardiol, 2001, vol. 37, pp. 992--997
2. A meta-analysis of the association between adherence to drug therapy and mortality. SH. Simpson, DT. Eurich, SR. Majumdar,  et al., BMJ, 2006, vol. 333, pp. 15--

Related Links
Not taking Your Meds Can Be Dangerous to Your Health
Statins Work Even When the Cholesterol Isn't Raised
Risk of Stopping High Blood Pressure Medication

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