Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324 168 participants from randomised trialsDr Sripal Bangalore, MD. etal
Publication History:
Published November 30, 2010
DOI: 10.1016/S1470-2045(10)70260-6
SummaryBackgroundThe risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical trials.
MethodsWe undertook traditional direct comparison meta-analyses, multiple comparisons (network) meta-analyses, and trial sequential analyses. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from 1950, to August, 2010, for randomised clinical trials of antihypertensive therapy (ARBs, angiotensin-converting-enzyme inhibitors [ACEi], 汕 blockers, calcium-channel blockers [CCBs], or diuretics) with follow-up of at least 1 year. Our primary outcomes were cancer and cancer-related deaths.
FindingsWe identified 70 randomised controlled trials (148 comparator groups) with 324 168 participants. In the network meta-analysis (fixed-effect model), we recorded no difference in the risk of cancer with ARBs (proportion with cancer 2﹞04%; odds ratio 1﹞01, 95% CI 0﹞93每1﹞09), ACEi (2﹞03%; 1﹞00, 0﹞92每1﹞09), 汕 blockers (1﹞97%; 0﹞97, 0﹞88每1﹞07), CCBs (2﹞11%; 1﹞05, 0﹞96每1﹞13), diuretics (2﹞02%; 1﹞00, 0﹞90每1﹞11), or other controls (1﹞95%, 0﹞97, 0﹞74每1﹞24) versus placebo (2﹞02%). There was an increased risk with the combination of ACEi plus ARBs (2﹞30%, 1﹞14, 1﹞02每1﹞28); however, this risk was not apparent in the random-effects model (odds ratio 1﹞15, 95% CI 0﹞92每1﹞38). No differences were detected in cancer-related mortality for ARBs (death rate 1﹞33%; odds ratio 1﹞00, 95% CI 0﹞87每1﹞15), ACEi (1﹞25%; 0﹞95, 0﹞81每1﹞10), 汕 blockers (1﹞23%; 0﹞93, 0﹞80每1﹞08), CCBs (1﹞27%; 0﹞96, 0﹞82每1﹞11), diuretics (1﹞30%; 0﹞98, 0﹞84每1﹞13), other controls (1﹞43%; 1﹞08, 0﹞78每1﹞46), and ACEi plus ARBs (1﹞45%; 1﹞10, 0﹞90每1﹞32). In direct comparison meta-analyses, similar results were recorded for all antihypertensive classes, except for an increased risk of cancer with ACEi and ARB combination (OR 1﹞14, 95% CI 1﹞04每1﹞24; p=0﹞004) and with CCBs (1﹞06, 1﹞01每1﹞12; p=0﹞02). However, we noted no significant differences in cancer-related mortality. On the basis of trial sequential analysis, our results suggest no evidence of even a 5每10% relative risk (RR) increase of cancer and cancer-related deaths with any individual class of antihypertensive drugs studied. However, for the ACEi and ARB combination, the cumulative Z curve crossed the trial sequential monitoring boundary, suggesting firm evidence for at least a 10% RR increase in cancer risk.
InterpretationOur analysis refutes a 5﹞0每10﹞0% relative increase in the risk of cancer or cancer-related death with the use of ARBs, ACEi, 汕 blockers, diuretics, and CCBs. However, increased risk of cancer with the combination of ACEi and ARBs cannot be ruled out.
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