Issue 26 / 9 July 2012

US research showing high doses of antihypertensives significantly decrease mortality in patients with congestive heart failure highlights the importance of pushing for the highest tolerable dose, according to Australian experts.

The population-based, retrospective study, published in Archives of Internal Medicine, examined data on more than 43 000 patients after discharge following their first CHF-related hospital admission. (1)

The researchers followed patients who filled prescriptions for any angiotensin II-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) after discharge. They found 73% filled a prescription for an ACE inhibitor and 27% for an ARB. Overall, 29% received a low-dose of either drug.

Patients on the highest doses of either drug had the best outcome, particularly those on high doses of ACE inhibitors, who had significantly reduced mortality and composite end point (comprising reduced all-cause mortality or CHF readmission). Those on the lowest doses of either drug were found to have a significantly higher mortality and CHF readmissions than those on medium and high doses.

“Our results demonstrate that target doses of ACE inhibitors or ARBs are reached in only one-third of patients with CHF. Physicians should strive, whenever possible, to treat patients with CHF with high doses of ACE inhibitors or ARBs to improve outcomes”, the researchers wrote.

Professor Henry Krum, director of the Centre of Cardiovascular Research and Education in Therapeutics at Monash University, told MJA InSight that low doses of drugs were invariably associated with increased events, especially in community-based trials, “because the sickest patients are the ones who can only tolerate the lowest doses of drugs”.

“Having said that, the guidelines do push for the highest tolerated dose of these drugs, so that is a good message [from this study]”, Professor Krum said.

In the study, patients on low doses were more likely to have renal disease, while those on high doses were more likely to have hypertension and diabetes than those on low and medium doses.

Professor Derek Chew, professor of cardiology at Flinders University, agreed that the problem with the analysis was that patients who could tolerate high doses of medication were clearly of much lower risk than those who could only tolerate low doses.

Despite the limitations of the study, Professor Chew said it did suggest that where possible, physicians should push for higher doses of these drugs in CHF patients.

“We should always strive for the evidence-based dose. [However,] the real issue is that the patients who need the therapies the most are excluded from clinical trials and more often can’t tolerate the higher doses”, Professor Chew said.

– Kath Ryan

1. Arch Intern Med 2012; Online 2 July

Posted 9 July 2012