By: Dr. Geoffrey Modest
A large meta-analysis recently looked at studies of blood pressure in diabetics (baseline BP and achieved BP) and clinical events (all-cause mortality, cardiovascular events, coronary heart disease, stroke, heart failure, retinopathy, new or worsening albuminuria, and renal failure) –see JAMA.2015;313(6):603-615. 40 studies were found with “low-risk of bias”, with 100,354 patients.
Results:
–Each 10-mm decrease in systolic BP was associated with:
–significantly lower all-cause mortality: RR 0.87 [0.78-0.96] and absolute risk reduction per 1000 patient-years ARR of 3.16 [0.90-5.22]
–significantly lower cardiovascular events: RR 0.89 [0.83-0.95] and absolute risk reduction per 1000 patient-years ARR of 3.90 [1.57-6.06]
–significantly lower coronary heart disease : RR 0.88 [0.80-0.98] and absolute risk reduction per 1000 patient-years ARR of 1.81 [0.35-3.11]
–significantly lower stroke: RR 0.73 [0.64-0.83] and absolute risk reduction per 1000 patient-years ARR of 4.06 [2.53-5.40]
–significantly lower albuminuria: RR 0.83 [0.79-0.87] and absolute risk reduction per 1000 patient-years ARR of 9.33 [7.13-11.37]
–significantly lower retinopathy: RR 0.87 [0.76-0.99] and absolute risk reduction per 1000 patient-years ARR of 2.23 [0.15-4.04]
–differences in heart failure and renal failure did not reach significance, though reanalysis of heart failure to include trials not standardized to a 10-mmHg BP reduction did reach significance
–When mean initial systolic was >=140 mmHg vs <140, for essentially all of these outcomes, there was significant relative risk reduction only if initial systolic was >= 140 (other than stroke and albuminuria, where BP reductions were also significant in those <140)
–When achieved systolic was >=130 vs <130, again, there was significance only for those with systolic >=130 (again, other than stroke and albuminuria, where achieved systolic <130 was also beneficial)
–In looking at the results by drug class, there were few difference. Diuretics were better for the outcome of heart failure (largely through the results of ALLHAT); ARBs were also beneficial (but there were only 2 trials with ARBs); ACE-I were worse, and again, I suspect, ALLHAT played a role; calcium channel blockers had worse heart failure but better stroke outcomes.
One issue not addressed is the BP goal in people with very high blood pressure. Should they have the same target as those with only marginally increased blood pressure? Or are they different, either pathophysiologically different because they develop such high pressures, or perhaps because the very high blood pressure itself changes them physiologically (eg by leading to more vascular remodeling, perhaps changes in local vascular autoregulation which could affect the blood flow to local tissues …).
So, this study differs from and adds a bit of nuance to the recent JNC8 recommendations. Whereas JNC8 raised the BP threshold to treat diabetics from a systolic of >130 to >140, this study challenges that by suggesting a systolic goal of 130 and goes further to suggest that for some targets (eg stroke, albuminuria, and marginally for retinopathy), an even lower blood pressure may be better. Perhaps some risk stratification may be useful in assigning a blood pressure goal (eg, those at higher risk of stroke or kidney/eye disease should have an even lower goal. 120??). JNC8 largely based their recommendations for diabetics on the ACCORD trial, which did find an increase in adverse events in the group with tighter BP control (achieved BP of 119 vs 133). But the absolute rate of adverse events was low and dwarfed by the potential improved outcomes noted in the above study. So, how do we reconcile these differences (and, more importantly, how should we treat patients?). First and foremost, guidelines are just guidelines and should not supercede clinical judgment and the specifics of the patient in front of you. One perhaps relevant point is that the JNC8 recommendations come out of one specialty society (and not from the Natl Heart, Lung, and Blood Institute of NIH, which developed prior JNC guidelines). In terms of individualizing therapy, for some patients it might be better to have a lower target (especially younger patients, who can easily achieve lower blood pressure without adverse events). My major caution is that many older diabetics have significant autonomic dysfunction and very frequently orthostatic hypotension. So, I really think it is important to check orthostatics on diabetics regularly (at least yearly), and shoot for a higher blood pressure goal if needed to maintain an adequate standing pressure. But consider lower goals in those who tolerate the medications, especially if they have a reasonably long life expectancy. And, as per usual, continue to reinforce lifestyle changes (and I have seen several patients come off meds by losing weight, doing exercise, eating well…)
For JNC 8 review, see here.