Drug Topics - January 28, 2008 - (Page 14) 14 DRUG TOPICS JANUARY 28, 2008 www.drugtopics.com Cover Story of newly diagnosed hypertenDT CAPSULE sive patients do not receive drug treatment in the first year of their diagnosis. “We believe that physicians are prescribing lifestyle modifications to the majority of these patients; however, this non-pharmacologic approach is contrary to the advice of thought leaders, who only recommend a two- to three-month trial of lifestyle interventions,” said Jeremy Goldman, M.D., analyst at Decision Resources. Compliance is still considered one of the biggest barriers to treating HTN—even in highly educated patients. Just prior to undergoing coronary bypass surgery, former President Bill Clinton publicly admitted to mistakenly stopping his own medication after assuming that his BP was well controlled. Noncompliance appears to be particularly common among patients who have reached target BP levels and believe that medication is no longer needed. and myocardial fibrosis, may improve diastolic function to a greater extent than other antihypertensive agents. VALIDD results, however, showed that valsartan was not more effective than non-RAAS antihypertensives in improving diastolic function, although it was associated with significantly greater improvement in isovolumetric relaxation time and systolic longitudinal velocity. Critics of the study point out that while the absence of an additional effect of valsartan might be disappointing, this study does not preclude a benefit of RAAS inhibition in a population with more advanced left ventricular remodeling. Marc Cohen, M.D., FACC, appears to agree with the concept of prioritizing BP reduction over other facets of therapy, stressing that clinicians should essentially “use whatever antihypertensive gets the job done.” Cohen is a director of the division of cardiology at Newark Beth Israel Medical Center in New Jersey. Of a somewhat different opinion, Weber indicated that there “is evidence that different antihypertensive classes have subtle advantages that are independent of their BP lowering actions.” And, in fact, the AHA guidelines point out that for secondary prevention in patients with compelling indications (e.g., ischemic heart disease), not all drug classes confer the same effects on clinical endpoints. In a review published in the August issue of the Lancet, Messerli et al referred to evidence suggesting that CAD is best prevented by ACE inhibitors, CCBs, and thiazide diuretics; stroke by angiotensin-receptor blockers (ARBs), CCBs, and diuretics; and congestive heart failure by diuretics, ACE inhibitors, and ARBs. The authors do caution, however, that most of the evidence for these recommendations is based on metaanalyses—the largest of which being the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), which has suggested that antihypertensive benefits come from specific agents as opposed to BP reductions. The latest BPLTTC findings, which diverge significantly from the VALIDD implications, indicate that BP-independent effects of ACE inhibitors are equivalent to the effect of an additional 3 mm Hg reduction in systolic BP. The BPLTTC results also add credence to data from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), which showed that amlodipine and perindopril significantly reduced total and cardiovascular mortality in comparison with atenolol and a thiazide diuretic. These findings appear to redeem RAAS inhibitors, which researchers have kept a close eye on AHA guidelines consider BP lowering to be more important than the choice of drug class. Agreeing to disagree The good news comes in the form of new guidelines, research, and FDA approvals, all of which offer insight into and the promise of better HTN management, but they also bring somewhat conflicting news. The American Heart Association (AHA) has made several points of distinction in its recently released scientific statement on the treatment of HTN for preventing and managing ischemic heart disease. For primary prevention of coronary artery disease (CAD), these guidelines recommend aggressive BP lowering to <140/90 mm Hg, or to <130/80 mm Hg in patients with risk factors, such as diabetes mellitus, chronic kidney disease, or known CAD. Patients with left ventricular dysfunction should be considered for an even lower BP target (<120/80 mm Hg). These goals appear rather ambitious compared with those of other guidelines, discussed below. In the context of primary prevention of atherosclerotic complications, authors of the AHA guidelines consider BP lowering to be more important than the choice of drug class. They remain unconvinced that certain classes of antihypertensive drugs may have greater anti-atherosclerotic actions than others. This thinking, which is somewhat contrary to the well-known JNC-7 concept of compelling indications, appears somewhat tied to a trial (VALsartan in Diastolic Dysfunction; VALIDD) published recently in the June issue of the Lancet. Researchers originally set out to prove that agents blocking the renin-angiotensin-aldosterone system (RAAS), which have the ability to reduce ventricular hypertrophy http://www.drugtopics.com
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