Making Sense Out of an Alphabet Soup of Hypertension Treatment Studies

Numerous randomized trials have evaluated antihypertensive regimens in various settings, including those complicated by at least one other vascular disorder. Among these trials are the Modification of Diet in Renal Disease (MDRD) Study in hypertensive patients with kidney disease; the Comparison of AMlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) Study and the INternational VErapamil-trandolapril STudy (INVEST) in patients with hypertension and coronary disease; and the Perindopril pROtection aGainst REcurrence of Stroke Study (PROGRESS) in hypertensive patients who have had a stroke. The Heart Outcomes Prevention Evaluation (HOPE) Study demonstrated that ramipril reduced cardiovascular (CV) events both in persons with diabetes who had vascular disease and in those who had normal blood pressure.

Despite the wealth of data from these and other prospective, randomized, blinded studies, a key challenge remains: blood pressure is adequately controlled in only 30% of Americans with hypertension-related disease.¹

But what is the best way to address this problem? Is it the drug used, the level of blood pressure reached, or the blood pressure target and the regimen together? A recent review of a broad array of trials that studied various populations and medications offers some insights.²

WHAT THE EVIDENCE SHOWS
In some trials, drug selection matters. The MDRD Study as well as other trials in patients with renal disease (eg, the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL] Study) demonstrated that blockade of the angiotensin system is the best way to treat hypertension to slow progression of renal disease. In fact, in the IrBesartan diabetic Nephropathy Trial (IBNT), which compared irbesartan with amlodipine, systolic blood pressure was only 1 mm Hg lower in the irbesartan group than in the amlodipine group, but there was a 23% greater reduction in progression of renal disease.

In other trials, however, the drug used does not matter. A meta-analysis of 27 trials compared angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers (newer drugs) with diuretics and -blockers (older standbys). There was no difference between the newer and older agents in terms of CV end points-as long as blood pressure was lowered.

Dr John Forman, the author of the review, commented: "Blood pressure reduction per se has a tremendous beneficial effect on CV events. . . . Perhaps instead of laboring to determine whether 1 drug is marginally superior to another, we should focus our efforts to improving BP control in the community, resulting in more profound public health improvements."²

THE BOTTOM LINE FOR YOUR PRACTICE
Hypertensive persons who have renal disease should be treated with an agent that blocks the renin-angiotensin system. But there is no unequivocal recommendation for hypertensive patients with other vascular disorders, such as coronary disease or a history of stroke.

In most instances, the problem is that we are not treating aggressively enough. Remember, in one analysis, for every 10 mm Hg decrease in systolic pressure or 5 mm Hg decrease in diastolic pressure, there was a 40% reduction in the risk of death from stroke and a 30% reduction in coronary disease end points.³ The best advice is to lower blood pressure and not worry as much about which drug is doing the job.

References:

REFERENCES:1. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA. 2003;290:199-206.
2. Forman JP. Controversies in blood pressure. Nephrology Rounds. January 2007; 5(1). http://www.nephrologyrounds.org. Accessed March 20, 2007.
3. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.