Little Difference among Drugs Treating Long Term Elevated Blood Pressure

At a mean 8.8 years of follow-up in the trial, outcomes were nearly identical with the diuretic chlorthalidone as compared with the calcium channel blocker amlodipine (Norvasc) and the ACE inhibitor lisinopril (Prinivil, Zestril).

Paul Whelton, MD, MSc, of Loyola University Medical Center in Maywood, IL, reported that the only significant differences actually favored the diuretic.

Heart failure hospitalization and fatalities remained lower at 8.8 years with the diuretic compared with the calcium channel blocker (hazard ratio 1.12 for amlodipine, P=0.01).

Fatal strokes remained lower compared with the ACE inhibitor at 8.8 years (HR 1.20 for lisinopril, P=0.03).

The data "demonstrated some diminution of the differences between treatment effects of chlorthalidone and the newer agents, but provided no evidence that either amlodipine or lisinopril was superior to chlorthalidone in preventing major cardiovascular disease events," Whelton told attendees of the China Heart Congress and International Heart Forum in Beijing.

These findings largely matched the 10-year ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) results reported by other researchers at the 2009 American Heart Association meeting.

By that point, all differences between the treatment arms had been lost, with the exception of a 34% elevated heart failure risk with amlodipine.

The initial five-year analysis significantly favored the diuretic in several outcomes, showing elevated risk of heart failure with amlodipine (HR 1.38) and lisinopril (HR 1.20), and an elevated risk of stroke with lisinopril (HR 1.15).

The ALLHAT investigators have consistently pointed to cost as yet another advantage of thiazide-type diuretics. Generic diuretics cost $25 to $40 per year compared with up to $300 to $600 annually for newer brand-name hypertension drugs. However, since the study started, the calcium channel blocker and ACE inhibitor used have become available generically as well.

Joint National Committee (JNC7) guidelines give preference to diuretics as a first-line agent after lifestyle measures, although international guidelines have tended to disagree. But the message may simply be that the specific drug or method used doesn't matter much as long as it controls blood pressure, Stephen L. Kopecky, MD, of the Mayo Clinic in Rochester, MN, explained.

Kopecky stated that, "It can be lifestyle, it can be exercise, it can be weight loss, it can be not smoking and drinking… What we're finding over and over again is, it really is important getting your numbers under control no matter how you do it."

The ALLHAT trial was designed to compare the three classes primarily on occurrence of a composite endpoint of fatal coronary heart disease or nonfatal myocardial infarction.

The trial's initial five-year double-blind phase included 33,357 high-risk hypertensive patients ages 55 years or older randomized to treatment with one of the three drugs between 1994 and 2002.

A fourth arm using the alpha-blocker doxazosin (Cardura) stopped early because of elevated cardiovascular mortality, heart failure, and stroke risks and was not included in Whelton and colleagues' analysis.

All treatments were titrated to doses to reach a blood pressure under 140/80 mm Hg with additional protocol-designated medications added as second and third steps for those who required them.

After the conclusion of the randomized therapy period, passive surveillance through administrative databases continued for four to five years for a total follow-up experience of eight to 13 years from the time of randomization (mean 8.8 years).

The primary outcome during this extended period was cardiovascular disease mortality which showed no differences overall (HR 1.00 for amlodipine, P=0.89, and HR 0.97 for lisinopril, P=0.33).

• Note the commenter's emphasis that the amount of the blood pressure decrease is the major determinant of cardiovascular risk reduction in hypertensive patients, not the choice of antihypertensive drug.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The journal Work, August 2010