Drug combinations improve survival for patients with heart disease

May 31, 2017

This is the first large scale, long term trial to report the effect of different combinations of drugs to prevent deaths in patients with heart disease,

The study involved over 13,000 patients who were diagnosed with ischaemic heart disease between 1996 and 2003. Cases were patients with heart disease who died, while controls were patients with heart disease who were matched for age, sex, and year of diagnosis and were alive at the time their matched case died.

Treatments associated with the greatest reduction in deaths (83%) were statins (cholesterol lowering drugs), aspirin, and beta-blockers (a type of blood pressure lowering drug). Adding another type of blood pressure lowering (an angiotensin converting enzyme inhibitor) conferred no additional benefit.

Treatments associated with the smallest reduction were beta-blockers alone (19%) and angiotensin converting enzyme inhibitors alone (20%).

Combinations of statins, aspirin, and beta-blockers improve survival in high risk patients with cardiovascular disease, say the authors.

It has previously been proposed that these three treatments, along with folic acid, be combined into a "polypill" to be taken daily by everyone from age 55. These results support the synergic action of the polypill for people with pre-existing heart disease, but provide no evidence that it should be prescribed to all patients over 55, they conclude.

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Treatment was generally well tolerated. Despite similar improvements in metabolic control after 24 weeks, (HbA1c: -0.8 +/- 0.9% pioglitazone vs. -0.6 +/- 0.8% glimiperide) carotid IMT was reduced from baseline only in the pioglitazone group after both 12 weeks (-0.033 +/- 0.052mm in the pioglitazone treated patients vs. -0.002 +/- 0.047mm in the glimepiride-treated patients, p<0.01 between groups) and after 24 weeks of treatment (-0.054 +/- 0.059mm vs. -0.011 +/- 0.058mm, respectively, p<0.005 between groups).

In addition, insulin resistance was significantly improved in the pioglitazone group versus the glimepiride group (-2.2 +/- 3.4 vs. -0.3 +/- 3.3, p<0.0001 between groups). Changes in IMT correlated with improvement in insulin resistance were found to be independent from the improvement in metabolic control.

The pioglitazone group also realized an improvement in CRP (pioglitazone - 0.80 +/- 0.29 mg/L; glimepiride -0.14 +/- 0.23, p< 0.0005).

In parallel, a statistically significant improvement was seen in blood pressure in the pioglitazone group at 24 weeks (systolic -9.4 +/- 20.1 mmHg, p<0.0001 diastolic -4.4 +/- 11.2 mmHg, p=0.001), while the glimepiride group was unchanged from baseline (systolic -1.4 +/- 19.6 mmHg, p=0.2788, diastolic 1.2 +/- 11.2 mmHg, p=0.6919). The difference between blood pressure levels at 24 weeks between the pioglitazone and glimepiride groups was statistically significant (p<0.01).

Treatment with pioglitazone was associated with a higher number of cases of increased body weight (20 vs. 2; p<0.0001) and edema (21 vs. 2; p<0.0001). Two patients in the pioglitazone arm experienced a clinically significant deterioration in their preexisting cardiac insufficiency.

Findings from this study were initially reported during the American Heart Association's Scientific Sessions 2004 proceedings.