Key Learnings from Recent Hypertension Clinical Trials: What Do We Know Now?

Newswise — Data presented today at the American Society of Hypertension's Twenty Fourth Annual Scientific Meeting (ASH 2009) summarize the optimal initial antihypertensive treatment to reduce two of the most common and deadly cardiovascular events related to blood pressure ─ stroke and coronary heart disease. Researchers conducted two separate and stringent types of meta-analyses that included all clinical trials, including those done very recently, to better estimate the overall benefits achieved with initial drug treatments for hypertension. These analyses were completed for all long-term (> 1 year) clinical trials that compared outcomes when an antihypertensive drug was given as initial therapy. They concluded only angiotensin receptor blockers (ARBs) were not a significantly better choice than placebo or no treatment to prevent heart attacks, probably because this is the newest class of commonly-used medications, and had the smallest numbers of patients enrolled in the fewest trials. For stroke prevention, all antihypertensive drugs were superior to placebo or no treatment, but an initial diuretic, ARB or calcium channel blocker (CCB) was slightly but significantly better than a beta-blocker or angiotensin-converting enzyme (ACE) inhibitor.

"Since the last comprehensive meta-analysis of cardiovascular outcomes was published in 2003, more than 25 new comparative trials (involving more than 398,000 subjects overall) have been completed," said William J. Elliott, M.D., Ph.D., of RUSH Medical College, Chicago IL. "It was important for us to reexamine this wealth of data to help summarize this knowledge for clinical practice."

Initial Drugs for Coronary Heart Disease Prevention in Hypertensive PatientsAll types of initial antihypertensive drug therapy were significantly better at preventing coronary heart disease than placebo or no treatment, with the exception of the newest class of antihypertensive drugs, the ARBs. One possible explanation for this is that ARBs are the newest class of the drugs studied, have been a treatment option for only 12 trials (8 as initial therapy), with the fewest number of subjects with (1,518) and at risk for (41,807) heart disease. By contrast, -blockers have been studied in 20 trials, in which 2,429 of 61,170 subjects developed heart disease. Of all types of drugs tested, ACE inhibitors were numerically more effective than other classes, although the differences were not statistically significant. Researchers note that these findings confirm the suggestion in recent literature that ARBs may not be as effective at preventing heart attack as other antihypertensive drugs, while ACE-inhibitors are especially effective at preventing heart disease (with benefits that some believe are greater than their blood pressure-lowering effects).

Importantly, additional meta-analyses may help clarify the recent debate about diuretics spurred by the contrasting results from the ACCOMPLISH and ALLHAT trials. Researchers subdivided the trials that used different diuretics: chlorthalidone, hydrochlorothiazide/chlorothiazide and "other," and found no significant differences across the various diuretics in their ability to prevent heart attack or sudden cardiac death.

"These results suggest that there are some differences in heart disease prevention between the different types of antihypertensive drugs," said Dr. Elliott. "However, hypertensive patients who take most (and all generically-available) medications to lower blood pressure can rest assured, based on all available evidence, that antihypertensive drugs have been effective in preventing many types of cardiovascular diseases, including heart disease."

Initial Drugs for Stroke Prevention in Hypertensive PatientsAs with coronary heart disease, results of both meta-analyses produced very similar results regarding treatment of stroke. Researchers found that all types of antihypertensive drugs were statistically superior to placebo or no treatment. An initial diuretic was significantly better by about 55 percent, a beta-blocker by about 22 percent, and an ACE-inhibitor by about 16 percent. The differences between the initial diuretic, ARB, or calcium-channel blocker (CCB) were not significant. These results were relatively little changed after including 17 other clinical trials that enrolled patients who were not hypertensive or used "add-on" antihypertensive drugs (rather than initial therapy). Similarly, subdividing the studies by their use of "low-dose" or "high-dose" diuretics had a minimal effect on the overall results.

When researchers subdivided the trials that used different diuretics: chlorthalidone, hydrochlorothiazide/chlorothiazide or "other," no significant difference was found across the diuretics in their ability to prevent stroke.

Researchers concluded that while there are some differences in stroke prevention between the different types of antihypertensive drugs, the data suggest that diuretics and CCBs may protect better against stroke, but not against heart attack.

"While these and other meta-analyses have limitations, they do provide insights beyond those of single trials, helping us to better and more critically contrast and compare different approaches," said Dr. Elliott. "Ultimately, we hope these results can improve our understanding of how to effectively treat hypertension and ultimately impact health outcomes positively."

About the American Society of HypertensionThe American Society of Hypertension (ASH) is the largest U.S. professional organization of scientific investigators and healthcare professionals committed to eliminating hypertension and its consequences. ASH is dedicated to promoting strategies to prevent hypertension and to improving the care of patients with hypertension and associated disorders. The Society serves as a scientific forum that bridges current hypertension research with effective clinical treatment strategies for patients. For more information, please visit www.ash-us.org.