ARBs for the Treatment of Heart Failure: A Class Effect?
Study Objective: To examine the class effect of angiotensin II receptor blockers (ARBs) on mortality in patients with heart failure who were aged 65 years or older.
Design: Retrospective population-based study.
Data Source: Administrative database that stores information on hospital discharge summaries for the Canadian provinces of Quebec, Ontario, and British Columbia.
Patients: A total of 6876 patients aged 65 years or older who were discharged with a primary diagnosis of heart failure between January 1, 1998, and March 31, 2003, and who filled at least one prescription for an ARB within 90 days of discharge.
Measurements and Main Results: Times to all-cause death in patients receiving individual ARBs were compared. Models were adjusted for demographic, clinical, physician, and hospital characteristics; models were also adjusted for dosage categories, which were represented by time-dependent variables. The cohort of 6876 patients had a mean B1 SD age of 78 B1 7 years, and most (62%) were women. Losartan was the most frequently prescribed ARB (61%), followed by irbesartan (14%), valsartan (13%), candesartan (10%), and telmisartan (2%). Irbesartan, valsartan, and candesartan were associated with better survival rates than losartan (adjusted hazard ratios [HRs] and 95% confidence intervals [CIs] 0.65 [0.53–0.79], 0.63 [0.51–0.79], and 0.71 [0.57–0.90], respectively). No difference was noted in mortality in patients prescribed telmisartan compared with those receiving losartan (HR 0.92 [95% CI 0.55–1.54]).
Conclusions: Elderly patients with heart failure who were prescribed losartan had worse survival rates compared with those prescribed other commonly used ARBs. The absence of a class effect for ARBs is consistent with data showing pharmacologic differences among the drugs.
Randomized trials have shown that angiotensin II receptor blockers (ARBs), alone and in combination with angiotensin-converting enzyme (ACE) inhibitors, improve survival in patients with heart failure. Although ACE inhibitors are indicated as first-line treatment in heart failure, ARBs are being used increasingly in clinical practice. Despite the fact that not all ARBs have been studied in patients with heart failure, they may be used interchangeably on the assumption that a class effect exists. A class effect implies that all drugs in a class exert the same effects, whether positive or negative, on their target population. However, pharmacologic and dosing differences exist among the various ARBs, and these differences have the potential to affect their individual efficacy. Indeed, pharmacokinetic data suggest that losartan and its active metabolite may be the least potent and bioavailable compared with valsartan, irbesartan, and candesartan. At the clinical level, although results of a large meta-analysis suggested that all ARBs have comparable antihypertensive efficacy, several head-to-head comparisons suggest that irbesartan, candesartan, and telmisartan may control blood pressure better than does losartan, possibly due to their longer durations of action and optimum dosing regimens. To our knowledge, no study has compared several ARBs head-to-head to assess whether these differences influence mortality in patients with heart failure. Yet, these potential differences may have important implications for clinicians who need to choose an ARB when treating patients with heart failure and for policymakers who are concerned with the rising cost of drugs. We therefore designed a population-based study to examine the class effect of ARBs on mortality in patients with heart failure who were aged 65 years or older.
Study Objective: To examine the class effect of angiotensin II receptor blockers (ARBs) on mortality in patients with heart failure who were aged 65 years or older.
Design: Retrospective population-based study.
Data Source: Administrative database that stores information on hospital discharge summaries for the Canadian provinces of Quebec, Ontario, and British Columbia.
Patients: A total of 6876 patients aged 65 years or older who were discharged with a primary diagnosis of heart failure between January 1, 1998, and March 31, 2003, and who filled at least one prescription for an ARB within 90 days of discharge.
Measurements and Main Results: Times to all-cause death in patients receiving individual ARBs were compared. Models were adjusted for demographic, clinical, physician, and hospital characteristics; models were also adjusted for dosage categories, which were represented by time-dependent variables. The cohort of 6876 patients had a mean B1 SD age of 78 B1 7 years, and most (62%) were women. Losartan was the most frequently prescribed ARB (61%), followed by irbesartan (14%), valsartan (13%), candesartan (10%), and telmisartan (2%). Irbesartan, valsartan, and candesartan were associated with better survival rates than losartan (adjusted hazard ratios [HRs] and 95% confidence intervals [CIs] 0.65 [0.53–0.79], 0.63 [0.51–0.79], and 0.71 [0.57–0.90], respectively). No difference was noted in mortality in patients prescribed telmisartan compared with those receiving losartan (HR 0.92 [95% CI 0.55–1.54]).
Conclusions: Elderly patients with heart failure who were prescribed losartan had worse survival rates compared with those prescribed other commonly used ARBs. The absence of a class effect for ARBs is consistent with data showing pharmacologic differences among the drugs.
Randomized trials have shown that angiotensin II receptor blockers (ARBs), alone and in combination with angiotensin-converting enzyme (ACE) inhibitors, improve survival in patients with heart failure. Although ACE inhibitors are indicated as first-line treatment in heart failure, ARBs are being used increasingly in clinical practice. Despite the fact that not all ARBs have been studied in patients with heart failure, they may be used interchangeably on the assumption that a class effect exists. A class effect implies that all drugs in a class exert the same effects, whether positive or negative, on their target population. However, pharmacologic and dosing differences exist among the various ARBs, and these differences have the potential to affect their individual efficacy. Indeed, pharmacokinetic data suggest that losartan and its active metabolite may be the least potent and bioavailable compared with valsartan, irbesartan, and candesartan. At the clinical level, although results of a large meta-analysis suggested that all ARBs have comparable antihypertensive efficacy, several head-to-head comparisons suggest that irbesartan, candesartan, and telmisartan may control blood pressure better than does losartan, possibly due to their longer durations of action and optimum dosing regimens. To our knowledge, no study has compared several ARBs head-to-head to assess whether these differences influence mortality in patients with heart failure. Yet, these potential differences may have important implications for clinicians who need to choose an ARB when treating patients with heart failure and for policymakers who are concerned with the rising cost of drugs. We therefore designed a population-based study to examine the class effect of ARBs on mortality in patients with heart failure who were aged 65 years or older.
SHARE
