An epidemiological study suggests that people with hypertension taking a diuretic plus a calcium-channel blocker (CCB) may have a higher risk of myocardial infarction (MI) than those taking diuretics with beta-blockers or with ACE-inhibitors and angiotensin receptor blockers (ARB). Risk of stroke was similar.

Low dose diuretics are a mainstay of antihypertensive treatment and are recommended as the first-line therapy for many patients in both US and UK guidelines. There is no controlled trial evidence, however, on the optimum second-line drug. The authors of this reports therefore carried out a case-control study using data from a US Health Maintenance Organisation to compare clinical outcomes in patients with hypertension who were treated with low-dose diuretic plus another commonly-used antihypertensive drug. Cases were patients with hypertension who had a diagnosis of incident fatal or non-fatal MI  between January 1989 and December 2005 or a fatal or non-fatal stroke between July 1989 and December 2005 (excluding events complicating a medical or surgical procedure). Controls were treated hypertensive patients with no MI or stroke and were selected in the ratio between 2:1 to 3:1. Patients with existing cardiovascular morbidity or diabetes were excluded to minimise confounding by indication. Primary outcome was MI or stroke.

There were 1,305 eligible patients identified who were treated with a two-drug anti-hypertensive regimen; 211 who had a first MI, 142 who had a first stroke, and 952 controls. Of these, 629 were treated with diuretics plus beta-blockers, 273 with diuretics plus CCB, and 403 with diuretics plus ACE-inhibitors or ARB. As a result of the exclusion criteria, they were a relatively low-risk population.

Patients being treated with diuretics plus CCB had a higher risk of MI than those being treated with diuretic plus beta-blocker (adjusted odds ratio (OR) 1.98, 95% CI 1.37 to 2.87). Their risk of stroke however, was similar (OR 1.02, 95% CI 0.63 to 1.64). There was a suggestion that those treated with diuretics plus ACE-inhibitors or ARB may have had a lower risk of MI or stroke compared to the diuretic plus beta-blocker group, however the differences were not statistically significant.

The authors conclude that in this patient population, antihypertensive drug treatment including a diuretic plus CCB was associated with a higher risk of MI than treatments including diuretic plus beta-blocker or ACE-inhibitor / ARB. They note that as an observational study, the difference may be due to unmeasured confounding, however they note that there is a plausible explanatory mechanism and suggest that a randomised controlled trial is needed to identify the optimum second-line drug to be added to low-dose diuretic for hypertension.