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28 July 2010
Intensive blood pressure control in type 2 diabetes: the Blood Pressure Treatment arm of the ACCORD* study

Intensive antihypertensive therapy targeting a ‘normal’ blood pressure (i.e., systolic BP <120 mmHg) does not significantly reduce residual risk of major cardiovascular events in high-risk type 2 diabetes patients. There was, however, suggestion of benefit in reducing stroke incidence, compared with conventional blood pressure control.

The ACCORD Study Group
Summary
Comments & References
STUDY SUMMARY
Methods 4,733 type 2 diabetes patients enrolled in the ACCORD study with mean systolic blood pressure (BP) 130-180 mmHg at baseline were randomly assigned to intensive therapy (targeting a systolic BP <120 mmHg) or standard therapy (targeting a systolic BP <140 mmHg). A wide variety of blood-pressure lowering medications were permitted. The primary outcome was a composite of nonfatal myocardial infarction (MI), nonfatal stroke or cardiovascular death. Mean follow-up was 4.7 years.
Main results • At 1 year, mean systolic BP was 119 mmHg in the intensive therapy group versus 134 mmHg in the standard therapy group.
• Intensive blood pressure control did not significantly reduce risk of the primary outcome.
• Mortality rates (all-cause and cardiovascular) were similar in each group.
• Intensive BP lowering did significantly reduce the risk of incident stroke versus standard therapy, but was also associated with higher rates of serious adverse events attributed to blood pressure-lowering medication(s).

Endpoint Intensive vs. standard BP control, HR (95% CI) p-value
Primary 0.88 (0.73-1.06) 0.20 (NS)
Any stroke 0.59 (0.39-0.89) 0.01
Non-fatal stroke 0.63 (0.41-0.96) 0.03
Serious adverse events* 3.3% vs. 1.3% <0.001
*attributed to antihypertensive therapy

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.

References 1. Adler AI, Stratton IM, Neil HA et al. BMJ 2000;321:412-9.
2. Chobanian AV, Bakris GL, Black HR et al. JAMA 2003;289:2560-72 [Erratum, JAMA 2003;290:197].
3. Law MR, Morris JK, Wald NJ. BMJ 2009;338:b1665.
4. Cooper DeHoff RM et al. Rethinking lower BP goals for diabetics with documented coronary artery disease - findings from the INternational VErapamil SR - Trandolapril STudy (INVEST). ACC 2010; Abstract 3010-10.