Valsartan, amlodipine in high-risk patients
VALUE randomized 15,245 high-risk hypertensive patients to valsartan (Diovan) and amlodipine.15,37 Trial researchers sought to study the difference—for the same level of blood pressure reduction—between the 2 regimens in the incidence of cardiac events defined as sudden cardiac death, hospitalized heart failure, nonfatal MI, and emergency procedures to prevent MI. That said, the attained blood pressure was lower on the calcium channel blocker: 4.0/2.1 mm Hg at 1 month and 2.1/1.7 mm Hg at the end of study.
After 4.2 years, there was no significant difference in the primary endpoint of first cardiac event (10.6% valsartan/10.4% amlodipine; RR=1.04 [95% CI, 0.94–1.15]; P=.49). Diabetes was lower, but the rate of MI was higher on valsartan. After correction for the blood pressure difference, the composite of cardiac events, stroke, death, or MI was similar in the 2 groups.38
VALUE patients reaching adequate blood pressure control by 6 months fared better, regardless of drug type used. Thus demonstrating that the benefit from good blood pressure control was more important than the subtle differences between antihypertensive drugs. The better metabolic profile in the angiotensin receptor blocker arm did not translate into a reduction in adverse clinical disease.
The VALUE trial suggests (as did ALLHAT) that drugs targeting the reninangiotensin system do not provide special cardiovascular protection.10,15
Where to begin when there are coexisting conditions
Choosing an antihypertensive drug according to the clinical disease and target organ most at risk of damage is logical and in keeping with numerous guidelines.42-45 Thus, you’ll want to treat hypertensive patients with these conditions as follows:
- Angina pectoris. Therapy should include a beta-blocker or calcium channel blocker, given their definite antianginal and possible anti-atherosclerotic effects.16,46,47
- Prior MI. Start the patient on a beta-blocker.47
- Poor left ventricular function. Start the patient on a diuretic, and then add an ACE inhibitor and beta-blocker, as needed.10,49,50
- Prior stroke (or a patient at special risk of stroke). Begin therapy with a calcium channel blocker or a diuretic.33,34
- Diabetic proteinuria. An ARB or an ACE inhibitor is best suited to prevent and delay nephropathy.51-54
Consensus emerges from studies spanning 10 years
This objective review of the comparative hypertension drug trials shows that there are no great differences in the cardiovascular protective efficacy of the diuretics, beta-blockers, calcium channel blockers, ARBs, and ACE inhibitors.
There was no significant difference in the cardiovascular primary endpoint in 11 of the 13 trials reviewed, involving 91% of the randomized 168,593 patients (TABLE).4-8,10,11,13-17 Of the remaining 2 trials, the difference in ANBP2 just reached a P value of .05, while the result in LIFE was driven by a lower stroke incidence on ARB treatment that is not noted in any of the other studies involving an ARB or ACE inhibitor.4-6,10,12-15
Focus on controlling blood pressure with combination of drugs
Given the very large number of patients studied in these well-conducted trials, if there were any especially useful, or detrimental, cardiovascular effect of a particular class of antihypertensive drug, it would have been obvious by now. Since most patients will require multiple drugs, the equivalent protective efficacy of different antihypertensive drugs is reassuring and suggests that physicians should not worry too much about which drug to start the patient on.28 Rather, the emphasis should be on how best to reach adequate blood pressure control by combining several antihypertensive drugs.
Small blood pressure differences, big impact
In LIFE (losartan vs atenolol), ALLHAT (doxazosin, amlodipine, lisinopril vs chlorthalidone), VALUE (amlodipine vs valsartan), and ASCOT (amlodipine vs atenolol), where a secondary cardiovascular endpoint was lower in one of the treatment arms, it was always the arm with the lower achieved blood pressure that had the better clinical outcome.9-11,15,17
Report takes aim at America’s other drug problem: Poor adherence
Marya Ostrowski, JFP Editor
With only 50% of patients typically taking their medications as prescribed and the cost of poor adherence reaching an estimated $177 billion annually in direct and indirect health care costs, one medication safety group is saying enough is enough.
The National Council on Patient Information and Education (NCPIE), a nonprofit coalition that includes health professional associations, government agencies, and pharmaceutical companies, issued a report this summer detailing a 10-step action plan for reducing the adverse health and economic consequences of poor medication adherence.
The plan, developed by a panel of experts that NCPIE convened, calls on the government and health care community to, among other things:
- address the barriers to patient adherence for patients with low health literacy.
- develop a curriculum on medication adherence for use in medical schools.
- mount a unified national education campaign to make patient adherence a national health priority.
“Medication adherence is America’s new drug problem,” said Carolyn M. Clancy, MD, director of the Agency for Healthcare Research and Quality. AHRQ has been working with NCPIE, the FDA, and the National Consumers League to develop a public education campaign on medication adherence, according to Clancy. The NCPIE report helps to bolster those ongoing efforts, she said.
On the heels of the report, NCPIE is planning on releasing videos that will teach seniors about properly taking their medications, according to Ray Bullman, NCPIE’s executive vice president.
To learn more about NCPIE’s initiatives, or for a copy of the report, Enhancing Prescription Medicine Adherence: A National Action Plan, point your browser to: www.talkaboutrx.org.