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7.1 Antihypertensive Therapy

Supplemental Information

Uncontrolled hypertension is a major cardiovascular risk factor that also accelerates the progression of diabetic nephropathy (Morrish, 1991).  When hypertension is identified, it should be aggressively treated to achieve a target blood pressure of less than 140/90 mmHg.  In many patients with diabetes, two or three or more antihypertensive agents may be needed to achieve this goal. The use of generic combination tablets (such as ACE plus calcium-channel blocker or beta-blocker plus diuretic) can reduce the complexity of the regimen and out-of-pocket costs.

The UKPDS, HOT, ADVANCE and ACCORD trials are all large randomized clinical trials that allow comparison of more stringent to less stringent blood pressure levels on major cardiovascular outcomes (ACCORD Study Group, The, 2010b; Zoungas, 2009; Hansson, 1998; UK Prospective Diabetes Study Group [UKPDS], 1998b). The UKPDS, HOT and ADVANCE trials all found reduced cardiovascular outcomes with lower achieved blood pressure levels. However, none of these trials achieved average systolic blood pressure levels below 130 mmHg (Table 2).  The ACCORD trial found no difference in major cardiovascular outcomes between a more intensive blood pressure intervention targeting systolic blood pressure < 120 mmHg compared to a more standard intervention targeting systolic blood pressure between 130 and 139 mmHg (Table 2).  The more intensive blood pressure regimen was associated with a small reduction in the rate of stroke, greater medication use and more serious adverse events (ACCORD Study Group, The, 2010b).

The above studies support a systolic blood pressure goal < 140 mmHg for people with T2DM. We would estimate that targeting a systolic blood pressure < 140 mmHg would result in an achieved blood pressure around 135 mmHg for most people.

Only the HOT trial specifically targeted diastolic blood pressure.  In the HOT trial, targeting a lower diastolic blood pressure was associated with fewer cardiovascular events in subjects with T2DM. The average achieved diastolic blood pressure values in the three HOT intervention arms ranged from 81-85 mmHg (Table 2).  Based on results from the ADVANCE and ACCORD trials, it appears likely that achieved systolic blood pressure values in the mid-130 range will be associated with diastolic blood pressure values well below 80 mmHg.

The general recommendation from The 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) to treat to a goal of a blood pressure < 140/90 mmHg does not preclude setting individual patient goals lower than that based on patient characteristics, comorbidities, risks or the preference of an informed patient (James, 2014).

Table 2. Comparison of Goal to Mean Achieved Blood Pressure Levels in Randomized Trials of Blood Pressure Control in People with Type 2 Diabetes

While ACE inhibitors and ARBs are preferred first-line therapy, two or more agents (to include thiazide diuretics) may be required. For patients with T2DM, thiazide diuretics in the treatment of hypertension may reduce cardiovascular events, particularly heart failure (James, 2014; Wing, 2003; ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, 2002; Heart Outcomes Prevention Evaluation Study Investigators, The, 2000; Alkharouf, 1993; Lewis, 1993).