Cardioprotection in diabetes

Achieving Cardiovascular Protection In Type 2 Diabetes Management

News - Mar. 30, 2011

Erland Erdmann, Professor of Cardiology, University of Cologne, Germany


Seven thousand deaths were directly attributed to diabetes in the UK in 2001, however this is a vast underestimate of the true mortality figures, since the cause of death of diabetics is usually recorded as that of the associated co-morbidities. The WHO estimate for developed countries is that 5 times more unattributed deaths occur as the direct result of diabetes1, equating to 35,000 UK deaths, representing 1 in 20 of the UK all-cause total. The greatest cause of mortality in T2DM is as a result of macrovascular events, comprising of CHD (~36%), cerebrovascular disease (~22%) and general atherosclerosis (~3%)2. The overall macrovascular event rate in diabetes is 5-8% per annum for MI, stroke or death3, whilst the recent BARI trial data has reported that the annual mortality rate following PCI or CABG is 2-6% in diabetic patients4. Hence for the cardiologist, the diabetic patient is a high-risk patient, having double the risk of non-diabetics, with death, MI, and stroke determining the patient’s outcome. The STENO-2 trial has demonstrated that a multi-factorial intervention is helpful in reducing mortality5, but only after 8 to 9 years, the 2 mortality curves diverge and it takes a long time for patients to be treated well, until benefit is observed.

Current Situation

The most recent European Heart Survey has reported that patients are still not treated optimally, with only 50-60% of patients receiving ACEI and statins6 (Figure 1). At the same time, the German DUTY register of 51,000 diabetics revealed that more than 54% had an HbA1c >7%, blood pressure exceeded 140/90 mmHg in 65% and LDL-C was >100mg/dl in 84%7, revealing that these patients are not achieving guideline goals and this is a matter of some concern. Yet even when patients are treated well, diabetic patients continue to suffer high event rates, evidenced in the BARI-2D trial, in which patients maintained an acceptable HbA1c level (7.5%), LDL 80mg, BP 125/70 mmHg, GFR 70 ml/min and mean BMI of 32 kg/m2. Despite this, the event rates remained high over the 5 year trial, reporting MACE at 24%, CHF 22% and mortality at 12%8. ACCORD and ADVANCE failed to demonstrate that tight glucose control alone improves macrovascular risk, whilst the combination of metformin and sulphonylureas (SUs) might have actually increased CV risk9. As a result of the high CV risk in such patients and the negative outcome results seen with the older conventional anti-diabetic agents, it is important to give more attention to positive outcome studies, such as seen with pioglitazone.

A recent retrospective cohort of 19,000 patients has reported that, compared to other oral antidiabetic drugs, thiazolidendiones (TZDs) reduced all cause mortality by 46% over a 6 year sample period10 (Table 1). Notably, when separating these data into rosiglitazone versus pioglitazone, it appeared that the benefit on mortality outcomes was due only to pioglitazone, since it alone reached significance, and since this study was funded by the National Health, Lung and Blood Institute and by the NIH, it is unlikely that there were outside interests affecting results10 . Further evidence for the superiority of pioglitazone over rosiglitazone comes from the open-label RECORD study, comparing rosiglitazone with metformin and SUs, in which rosiglitazone failed to demonstrate any advantage in the rates of CV death or CV hospitalisation and there were no significant changes in the rate of MI or stroke11. Heart failure (HF) rates were found to be elevated in RECORD and upon investigating which of the patients were more vulnerable, it was noted that in HF patients the presence of baseline IHD, angina, stroke and the use of diuretics, CCBs, antiplatelet medication, beta-blockers and proteinuria were double that of controls12. This indicates that it is high CV risk patients who are more likely to sustain HF with rosiglitazone treatment.

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