ACCORD BP History and Rationale
The ACCORD Trial began in September of 1999. At the time of the trial start date (not publication date which occurred later during the reign of JNC 7), JNC6 was the current blood pressure guideline which recommended targeting a blood pressure of <140/90mmHg. It was known that diabetes increased the risk for CV events at every level of systolic or diastolic blood pressure, incurring increased risk at even prehypertensive BP levels. Despite this, the available trials did not support BP targets below the standard recommendation of <140/90.
The HOT and UKPDS trials had provided the strongest guidance for BP targets. The HOT Trial included a subgroup of patients with diabetes which showed a reduction in major CV events in the group targeted to a DBP <80mmHg, but the achieved BP in this group was 144/81mmHg. The UKPDS Study randomized patients with HTN and diabetes to tight BP control of <150/85mmHg or less tight BP control of <180/105mmHg. Strokes were reduced by 44%, microvascular endpoints were reduced by 37% in the tight BP control group. The achieved BP in the tight BP group in UKPDS was 144/82mmHg. On the basis of these trials and other trials, there was benefit to lowering SBP to <140mmHg, but there was no apparent benefit to more aggressive goals.
The ACCORD investigators chose to evaluate the benefit of more aggressive BP lowering. In addition, After the ACCORD Study began, JNC 7 was published in 2003 and it’s guidelines provided an even better justification for this trial. Despite a paucity of strong evidence, JNC 7 recommended a goal BP of <130/80 for patients with DM and HTN. This was somewhat unfounded and so the ACCORD investigators went out to see if there was actual benefit to this degree of BP lowering.
JNC PUBLICATION DATES
JNC 8: 2014
JNC 7: 2003
JNC 6: 1997
JNC 5: 1992
JNC 4: 1988
JNC 3: 1984
JNC 2: 1980
JNC 1: 1976
ACCORD BP DESIGN
The main question for this trial was if, in patients with T2DM at high risk for CV events, does intensive BP control (SBP <120 mmHg) reduce rates of nonfatal MI, nonfatal stroke, or CV mortality when compared to standard BP control (SBP <140 mmHg)? The ACCORD BP trial was a part of a much larger trial when tested three complementary medical treatment strategies for reducing CV morbidity and mortality in patents with type 2 diabetes. The overall ACCORD Trial was a randomized, multicenter trial which recruited 10,251 patients. It followed a double 2x2 factorial trial testing the interventions of BP targets as noted, intensive vs standard glycemic control (HbA1c <6% vs 7-7.9%), and statin+fibrate vs statin alone).
The ACCORD BP trial, however, enrolled 4733 patients and randomized them to intensive (SBP <120) vs standard (SBP <140). The reason it used a BP of <140/90 for the standard BP group was that it was based off JNC 6 guidelines when the trial was desinged (not JNC 7 guidelines which came out part way through the ACCORD Trial). BP was measured by AOBPM. Patients with a Cr >1.5 were excluded. Mean follow up was 4.7 years. Overall, intensive BP control did not reduce the primary outcome of the composite goal of nonfatal MI, nonfatal stroke, or CV mortality. In addition, the intensive BP target was associated with more serious adverse events including hypotension, bradycardia/arrhythmia, hyperkalemia , hypokalemia, elevatrion in serum creatinine. Conversely, intensive BP control did reduce the risk of the secondary outcomes of total stroke as well as nonfatal stroke.
Overall, this trial showed no benefit for intensive BP control for the primary outcome. The trial did have limitations which included possibly inadequate follow up. Longer follow-up may have detected benefit. Secondly, the event rate for primary outcomes in the standard BP group was also almost 50% lower than the expected. Lastly, there was a high prevalence of statin use among patients recurted to the overall ACCORD Trial and these patients were directed towards the ACCORD lipid trial. This reduced the power of the ACCORD BP trial and this can be seen in the wide confidence interval for the primary outcome.
CONTRIBUTION TO THE LITERATURE
This trial contributed to JNC8’s recommendation for a relaxed goal BP of <140/90 mmHg for patients with diabetes and hypertension (as compared to JNC 7 recommendation for <130/80 mmHg.
REFERENCES
The ACCORD BP Trial: ACCORD Study Group. (2010). Effects of intensive blood-pressure control in type 2 diabetes mellitus. New England Journal of Medicine, 362(17), 1575-1585.
ACCORD BP Trial PMID: 20228401
Other references: Cushman, W. C., Grimm Jr, R. H., Cutler, J. A., Evans, G. W., Capes, S., Corson, M. A., ... & Basile, J. N. (2007). Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. The American journal of cardiology, 99(12), S44-S55.
Useful summaries of the ACCORD BP Trial: