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COMMENT

Despite best treatment efforts, individuals with type 2 diabetes remain at high residual vascular risk. The Action to Control Cardiovascular Risk (ACCORD) trial aimed to address this unmet clinical challenge by evaluating whether intensifying treatment of glycemia (ACCORD glycemia arm, prematurely discontinued) or blood pressure (ACCORD BP arm) or extending dyslipidemia management with addition of fenofibrate to simvastatin regardless of baseline non-LDL levels (ACCORD Lipid arm) could impact residual vascular risk.

Recommendations versus evidence for intensive BP control in diabetes

Previous studies have shown that cardiovascular risk in diabetes patients is continuous across the range of systolic BP.1 This prompted the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) to recommend a target BP goal of <130/80 mmHg.2 However, the evidence base to support this recommendation is limited. Therefore ACCORD BP aimed to evaluate whether intensive blood pressure lowering can reduce residual cardiovascular risk in type 2 diabetes patients.

Intensive BP control and residual cardiovascular risk

Overall, the results of ACCORD BP are somewhat mixed. While lowering systolic BP to levels below current recommendations (<120 mmHg) does not impact residual risk of major cardiovascular events, the study did suggest some benefit in reducing risk of stroke. These findings are consistent with a recent meta-analysis which showed that reducing systolic BP by 10 mmHg reduced stroke incidence by 41% in randomized clinical trials and by 36% in observational studies.3

However, caution in interpreting these results is warranted. Firstly, ACCORD BP was underpowered as the event rate in the standard therapy group was almost 50% lower than expected. Second, the number of incident stroke events was low (36 in the intensive therapy group vs. 62 in the standard therapy group). Thus, the possibility that these results were due to chance cannot be discounted. Thirdly, it is possible that the trial duration was too short to discern the benefits of intensive blood pressure lowering therapy, given that patients were already receiving current standards of care, including background statin. Finally, it is noteworthy that intensive blood pressure control was also associated with increased rates of developing serious complications typically attributed to antihypertensive treatment, including hypotension, syncope, heart rate disturbances, elevated potassium levels and/or renal dysfunction.

Further, a retrospective analysis of the INVEST (International Verapamil SR-Trandolapril)4 study in 6,400 type 2 diabetes patients with coronary artery disease, adds supports to the ACCORD BP findings. Although patients who achieved a systolic BP of 130-140 mmHg (usual care) had a better outcome than those with values >140 mm Hg, there was no additional benefit observed in the group achieving target systolic BP (< 130 mmHg).

In conclusion, ACCORD BP shows that intensive blood pressure lowering to achieve normalization of systolic BP (<120 mmHg) does not sufficiently impact residual cardiovascular risk in type 2 diabetes patients.

Taking into account the study limitations, there remains a need for additional strategies to reduce residual cardiovascular risk in high-risk type 2 diabetes patients managed according to current standards of care.