How do calcium channel blockers compare with beta-blockers, diuretics, and angiotensin-converting enzyme inhibitors for hypertension? - Patient-Oriented Evidence that Matters - Brief Article

Journal of Family Practice, May, 2002 by Rex W. Force

Opie LH, Schall R. Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy. J Am Coll Cardiol 2002; 39:315-22.

* BACKGROUND Calcium channel blockers are used extensively in the treatment of hypertension. The authors systematically reviewed recent large, long-term trials that compared calcium channel blockers with beta-blockers or diuretics. A secondary analysis compared calcium channel blockers with ACE inhibitors in hypertensive patients with diabetes.

* POPULATION STUDIED The patients in this meta-analysis were pooled from 3 large European, multicenter studies (n = 21,611), that compared calcium channel blockers with diuretics or beta-blockers in elderly men and women with hypertension. A separate analysis included 3 smaller studies, bringing the total patients to 24,322. Most of these patients did not have active cardiovascular disease, including coronary artery disease and left ventricular hypertrophy; approximately 25% smoked; and approximately 50% had hypercholesterolemia. Only 1318 were included in a separate analysis of calcium channel blockers and ACE inhibitors in patients with hypertension and diabetes.

* STUDY DESIGN AND VALIDITY This was a metaanalysis of several randomized, controlled studies, which were double-blinded or assessed by a committee blinded to treatment assignment. Patients were followed for at least 2 years. The studies evaluated patients for major cardiovascular events, including myocardial infarction (MI), stroke, heart failure, and death. In the 3 major trials, target blood pressures were < 140/90 mm Hg, < 160/95 mm Hg, and < 90 mm Hg diastolic, respectively.

This meta-analysis was well done. Although the authors did not provide their specific search strategy, they included pertinent mega-trials of calcium channel blockers compared with the gold standard therapies for hypertension. Additionally, the authors rigorously evaluated the quality of the trials, tested the data for homogeneity, and corrected for multiple comparisons. The blood pressure goals in the studies were heterogeneous, possibly influencing event rates in the trials and limiting generalization of the data to typical clinical practice. The inability to generalize data was particularly true in the diabetes group analysis, in which patients achieved a mean systolic blood pressure of 159 mm Hg, which is considerably higher than the 130 mm Hg that the national hypertension guidelines and the American Diabetes Association currently recommend.

* OUTCOMES MEASURED The outcomes measured were fatal and nonfatal MI and stroke, development of congestive heart failure, and cardiovascular and total mortality.

* RESULTS Calcium channel blockers were associated with fewer nonfatal strokes than diuretics or betablockers (relative risk [RR]=0.751; 95% confidence interval [CI], 0.653-.864; absolute risk reduction [ARR]=0.9%; number needed to treat [NNT]=111). Fatal stroke rates were not different between the 2 groups (RR=0.918; 95% CI, 0.779-1.083). Also, there were fewer total strokes with calcium channel blockers (RR=0.869; 95% CI, 0.769-0.982; ARR=0.6%; NNT=167). Calcium channel blockers were associated with more nonfatal myocardial infarctions (RR=1.177; 95% CI, 1.011-1.370; absolute risk increase [ARI]=0.5%; number needed to harm [NNH]=200) and total myocardial infarctions (RR=1.182; 95% CI, 1.036-1.349; ARI=0.6%; NNH=167) compared with betablockers or diuretics. Rates of congestive heart failure, cardiovascular mortality, and total mortality were not different between the 2 groups.

In patients with diabetes and hypertension, ACE inhibitors were associated with fewer nonfatal, fatal, and total myocardial infarctions (RR=2.204; 95% CI, 1.501-3.238; ARR=6.0%; NNT=17 for total MIs) than were calcium channel blockers. The rates of development of congestive heart failure or stroke were similar with ACE inhibitors and calcium channel blockers. Cardiovascular and total mortality also were not different between the 2 groups.

RECOMMENDATIONS FOR CLINICAL PRACTICE

Calcium channel blockers are associated with slightly fewer strokes and slightly more myocardial infarctions compared with beta-blockers or diuretics. No significant differences in total or cardiovascular mortality between the classes of medications were noted in this meta-analysis. These data support the notion that calcium channel blockers are as safe as, but no more effective than, conventional treatments for hypertension. In diabetic patients, an angiotensin-converting enzyme (ACE) inhibitor should be used before a calcium channel blocker. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared the calcium channel blocker amlodipine and the ACE inhibitor lisinopril with the diuretic chlorthalidone in 30,000 elderly patients with hypertension and 10,000 with comorbid diabetes. Results of ALLHAT should be available by fall 2002. Meanwhile, primarily because of high costs, calcium channel blockers should remain fourth-line agents in the treatment of hypertension, "after diuretics, beta-blockers, and in diabetic patients particularly, ACE inhibitors.