Angiotensin II receptor blockers (ARBs) are coming under some disrepute due to several recent studies showing that they don't prevent heart disease or reduce death rates as well as other blood pressure medications.  They have been quite popular with American physicians thanks to heavy advertising promotions with the help of drug sales reps who visit doctor offices frequently and leave many goodies, including "free samples."  Since very few physicians keep a supply of inexpensive generic alternatives, expensive patent-protected medications usually are prescribed.

One problem is that the studies are written by physicians being paid by the manufacturer.  I have been very distressed by the fact that what is written is often written in a way to intentionally mislead the physician reader into thinking that the manufacturer's medication did better than it actually did.  

I admit to being misled.  A recent review in the British Medical Journal exposed facts that appear to show that ARBs are inferior when it comes to helping you live longer (BMJ  11/27/2004; 329:1248-1249).  I know that the names of big name American medical schools and physicians can be and are sometimes bought off by industry.  The FDA has also become much more corrupted since the Bush administration took over.  It makes it hard to know who is right.  Many of the original articles below were written in favor of ARBs.  The BMJ appears to have uncovered short-comings of ARBs by reanalyzing the data of the studies, themselves.

In any case, several ACE Inhibitors are very inexpensive generics, while ARBs are all more expensive.  The evidence shows that ACE Inhibitors are at least as good as ARBs and probably better at helping you live longer and happier.

Angiotensin II Antagonist Raised Heart Attack Risk: CHARM-Alternative: According to the BMJ, the 2,028 patient DB CHARM-alternative trial showed a significant 36% increase in myocardial infarction with candesartan (versus placebo) despite a reduction in blood pressure (4.4 mm Hg systolic and 3.9 mm Hg diastolic vs. placebo treatment).  Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-alternative trial. Lancet 2003;362: 772-6

ACE Inhibitors Better Than ARBs: In doing a meta-analysis of all relevant published studies (1966-August 2004), researchers concluded that ACE inhibitors have been definitively shown to prevent death. However, studies with ARBs in similar populations have not reduced death or heart attacks. Angiotensin Receptor Blockers versus ACE Inhibitors: Prevention of Death and Myocardial Infarction in High-Risk Populations. Epstein BJ, Gums JG. University of Florida, Gainesville, FL. Ann Pharmacother. 2005 Mar;39(3):470-80.

Angiotensin II Antagonist No Mortality Benefit: CHARM-Preserved: According to the BMJ, in a 4,539-patient 3-year DB PC study of chronic heart failure with preserved left-ventricular ejection fraction, candesartan reduced admissions for chronic heart failure by 13% but did not prevent death despite a mortality of 11.3% and a reduction in blood pressure of 7 mm Hg systolic and 3 mm Hg diastolic compared with placebo. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, et al; CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-preserved trial. Lancet 2003;362: 777-81

ARB Candesartan Reduces Death in Heart Failure: In the 37-month Candesartan in Heart failure Assessment of Reduction in Mortality (CHARM) study of 7,599 patients with heart failure, candesartan reduced both sudden death (HR 0.85; P=0.036) and death from worsening heart failure (HR 0.78, P=0.008). Effect of Candesartan on Cause-Specific Mortality in Heart Failure Patients. The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Program. Solomon SD, Wang D, Finn P, Skali H, Zornoff L, McMurray JJ, Swedberg K, Yusuf S, Granger CB, Michelson EL, Pocock S, Pfeffer MA. Harvard-Brigham and Women's Hospital. Circulation. 2004 Oct 4. Ed: With the two above reports being questioned by independent researchers, I don't know if this article can be relied upon.  I do know that many studies and reports by Harvard psychiatrists have been poorly done and misleading while others are critical to advancing scientific knowledge.

Angiotensin II Antagonist: Losartan Slightly Better Than Atenolol But Not for Heart Attacks: The LIFE study of 1380 isolated systolic hypertensive men found 25% decrease in mortality with larger decreases in cardiovascular disease, stroke, and diabetes in the 3 year DB study. Stevo Julius, U Mich, JAMA 9/25/02. However, losartan in the LIFE study did not reduce rates of myocardial infarction despite a 1.7 mm Hg lower pulse pressure compared with atenolol. BMJ  11/27/2004; 329:1248-1249. Losartan's advantage was primarily in fewer strokes. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. LIFE Study Group. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359: 995-1003.

Angiotensin II Antagonist: SCOPE Study Found No Advantage Over Placebo Except Fewer Strokes: In the 3.7-year DB PC study on cognition and prognosis in the elderly (SCOPE) covering 4964 elderly ages 70-84 with MMSE over 24 and BP over 160/90, candesartan was associated with a non-significant 10% increase in fatal plus non-fatal myocardial infarction despite lower blood pressure (3.2 mm Hg systolic and 1.6 mm Hg diastolic for candesartan vs. placebo). There was no difference in mortality or dementia score changes. Candesartan did well at lowering stroke risk. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, et al. The study on cognition and prognosis in the elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003;21: 875-86. 

Angiotensin II Antagonist: No Benefit to Heart or Mortality in RENAAL Study: In the RENAAL trial, a DB PC 3.4-year study performed in 1315 diabetic patients with nephropathy, the angiotensin receptor blocker losartan offered nephroprotection, but no reduction in cardiovascular mortality, although about 30% of patients died of a cardiovascular event and no decrease in overall mortality. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, et al. RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345: 861-9.

Angiotensin II Antagonist: Irbesartan More Heart Attacks, Strokes, and Death than Calcium Channel Blocker Amlodipine: In a DB PC 2.6-year study of 1715 hypertensives with diabetic nephropathy, irbesartan 300 mg/day protected kidney function, but seemed to have no impact on the 24% incidence of cardiovascular events (a secondary composite end point). Although irbesartan lowered blood pressure (4 mm Hg systolic and 3 mm Hg diastolic v placebo), no reduction occurred in myocardial infarction, stroke, or cardiovascular death. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345: 851-60. Compared with amlodipine, irbesartan was associated with a 36% increase in non-fatal myocardial infarction (P = 0.06), a 48% non-significant increase in stroke, and a 29% non-significant increase in death  despite similar blood pressure reduction. Angiotensin receptor blockers and myocardial infarction. Subodh Verma, Marty Strauss. Toronto General, BMJ  2004;329:1248-1249 

Angiotensin II Receptor Blocker Better than Calcium Channel Blocker for Elderly Systolic Hypertension: In a 421-patient 24-week DB study of angiotensin II receptor blocker valsartan 160 mg/day vs. calcium channel blocker amlodipine 10 mg/day for isolated systolic hypertension in the elderly, both meds did equally well but the rate of side-effects were 20% vs. 31% with edema 6% vs. 24%. A randomized, double-blind, active-controlled, parallel-group comparison of valsartan and amlodipine in the treatment of isolated systolic hypertension in elderly patients: The Val-Syst study. Malacco E, Vari N, Capuano V, Spagnuolo V, Borgnino C, Palatini P, Val-Syst Investigators. Clin Ther. 2003 Nov;25(11):2765-80.

Angiotensin II Antagonist Lowers Stroke, DM, Death: 9,193 men and women with hypertension in Scandinavia and the United States. All had signs of thickening of the heart's main pumping chamber, an ominous sign of blood pressure damage. Lancet 3/25/02

ACE Inhibitors and Angiotensin II Blockers Better for Sex Drive: A study reports that for men diuretics, alpha-agonists and beta-blockers appear to affect sexual function more than calcium antagonists and ACE inhibitors. Angiotensin II antagonists may actually improve sexual function. A small study of 105 women found the beta-blocker atenolol impaired sexual desire and performance while the angiotensin II antagonist valsartan did not. Roberto Fogari Am J Hypertens 1/2004;14:77-81

Thomas E. Radecki, M.D., J.D.

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