Target BP levels for patients with diabetes, high-risk hypertension remain debatable

American College of Cardiology 60th Annual Scientific Sessions

NEW ORLEANS — The amount and quality of evidence indicating ideal target BP levels in patients with diabetes or high-risk hypertension was up for discussion at the American College of Cardiology 60th Annual Scientific Sessions.

“The current ACCORD trial was designed to answer the question of optimal BP control,” Stanley S. Franklin, MD, of the University of California, Irvine Heart Disease Prevention Program, said during a presentation here. “But targeting systolic BP to 119 mm Hg vs. 133.5 mm Hg did not reduce composite rate of CV events in ACCORD, so the crux of this debate is: Should office systolic BP be less than 140 mm Hg, less than 135 mm Hg or lower?”

Contradictory evidence

Franklin, who spoke in support of targeting BP below 130/80 mm Hg, cited population studies from the Prospective Study Collaboration Oxford Group that show that systolic BP correlates with cardiovascular risk to as low as 115 mm Hg at all ages. He also noted that the Framingham Heart Risk Equations indicate an additive effect of combining diabetes with hypertension and an even higher risk when combining with other risk factors, suggesting that BP levels are “only one part of global risk of assessment.”

In addition, Franklin said, stages of CV disease may yield different endpoints for therapy. “Indeed, the wide spectrum of disease over time may require different treatment thresholds and different treatment goals.”

Accuracy of BP measurements must also be taken into consideration, according to Franklin. The 11-country International Database on Ambulatory BP monitoring in relation to CV Outcomes (IDACO) study revealed that researchers found sustained hypertension in a little less than 50% of patients, white coat hypertension in more than 50% of patients and approximately 10% of clinic-normotensive patients had masked hypertension. About 73% of middle-aged to older patients, however, were misdiagnosed by clinic measurements, spurring Franklin to question whether a high rate of misclassification by office assessment played a role in recruitment for the ACCORD study.

Furthermore, another study denoted only a 5-mm Hg difference between patients with masked hypertension and normotensive patients. Results also revealed a statistically higher percentage of target organ damage, kidney disease or left ventricular hypertrophy in patients with masked hypertension, according to Franklin.

“Perhaps the question is not whether lower is better but if whether the earlier you diagnose and treat, the better,” he said.

Franklin stressed the importance of measuring standing BP and nocturnal dipping as well, highlighting one study that indicated a correlation between postural hypertension and increased stroke risk in certain patients, such as the elderly, patients with type 2 diabetes or those with peripheral neuropathy. He pointed out that, because of high rates of misclassification by clinic or office BP measurements, the American Heart Association and the American Society of Hypertension recommend beginning therapy with raised office BP, borderline or prehypertension in the presence of organ damage. In the absence of organ damage, home BP measurement can be valuable, Franklin said, noting that treatment may also be initiated if daytime ambulatory BP exceeds 135/85 mm Hg. Nevertheless, he warned against lowering BP too much in frail patients with diabetes.

The need for more data

In response, William C. Cushman, MD, chief of preventive medicine section at Veterans Affairs Medical Center in Memphis, Tenn., explained that no data confirm the benefits of targeting a systolic BP of 130 mm Hg in patients with diabetes or high-risk hypertension. The ACCORD trial, he noted, afforded robust data in a high-risk population of more than 4,700 participants. The systolic BP was lower than 140 mm Hg in the majority of participants in the standard BP goal group, which targeted a BP less than 140 mm Hg, he said. In the intensive therapy group, which targeted a systolic BP goal of less than 120 mm Hg, the average number of drugs required to achieve a systolic BP of 119.3 mm HG was 3.4 and slightly more than two in the regular therapy group. The benefits of attaining this target for the primary composite CVD outcome, however, did not reach statistical significance.

“Results of ACCORD and previous studies provide no conclusive evidence that BP should be reduced with antihypertensive drugs below 120 mm Hg or 130 mm Hg,” Cushman said. “These trials also do not conclusively prove that we shouldn’t aim for less than 120 mm Hg, but they provide the best evidence to date, and, therefore, do not offer conclusive evidence that we should do it.”

Moreover, Cushman emphasized that lowering BP targets would mean millions of new diagnoses of hypertension. These "new" patients will require therapy and monitoring, and those patients already diagnosed with hypertension will need more drugs and monitoring to reach desired BP levels. This may also have a negative effect in the form of a J-curve, Cushman said, and if treatment is neither harmful nor beneficial, then that poses other problems. Monitoring would become more frequent and costly while adverse event would also become more common.

“It could waste patients’ and payers’ resources and time, and possibly deflects us away from something we have the resources to do,” he said.

Adherence may also decline, according to Cushman. Patients who are already taking eight to 10 drugs, for example, may decide to stop buying certain medications to alleviate cost or just because they want to take fewer pills. Nevertheless, they may be making the wrong choices, he said.

Both Cushman and Franklin acknowledged that more research is needed in this area and expressed hope that future trials will provide more conclusive data. – by Melissa Foster

Disclosures: Dr. Cushman has served as a consultant for Takeda Pharmaceuticals, Sanofi Aventis, Bristol Meyers-Squibb, Novartis, Daiichi Sankyo and Theravance. Dr. Franklin reports no relevant financial disclosures. Dr. Vongpatanasin reports receiving research grants from the NIH and Forrest Research Laboratories.

For more information:

• Franklin S. Session 0140-4. Presented at: ACC 60th Annual Scientific Sessions; April 2-5, 2011; New Orleans.
• Cushman W. Session 0140-5. Presented at ACC 60th Annual Scientific Sessions; April 2-5, 2011; New Orleans.

This is a topic in hypertension in which we have to continue to do research. Obviously, as the two debaters pointed out, the method of blood pressure measurement is also important. In addition, the ACCORD trial so far has been done in diabetics and those with higher risks and whether that can be generalized to other hypertension populations, we don’t know, but I think it’s something that’s really worth looking into.

– Wanpen Vongpatanasin, MD
Associate Professor, University of Texas Southwestern Medical Center,
Dallas, TX