More evidence that NSAIDs are harmful to heart-failure patients

30 mar 2009- Further evidence that even commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) are harmful to heart-failure patients has come from a new study [1].

The study, published in the January 26, 2009 issue of the Archives of Internal Medicine, shows dose-related increases in risk of death and rehospitalization for heart failure or MI with all COX-2 inhibitors or other NSAIDs.

Lead author Dr Gunnar Gislason (Gentofte University Hospital, Hellerup, Denmark), commented to heartwire: "Although our study is observational, and you can never exclude all confounding factors, we have very consistent results estimated using two different statistical methods. And these results are similar to many other previous studies. In addition, we see a strong dose-related response. I think the data are very convincing."

And it is not just the COX-2 inhibitors that are the problem, as diclofenac showed a similar risk. "This is very disturbing, as this drug is so widely used and is available off prescription in many countries," Gislason noted.

He described the effect as "quite considerable." For example, for rofecoxib (Vioxx, Merck), the number of patients needed to treat for one year to cause one death was just nine, and the corresponding number for celecoxib (Celebrex, Pfizer) was 14 and diclofenac 11. "These numbers are very low," Gislason said, noting that for antihypertensive drugs, the number needed to treat for one year to save one life is in the range of 50 to 100. "Everyone agrees that it is worth treating hypertension. So the harmful effect of some NSAIDs is much greater than the beneficial effect of antihypertensive treatment."

Even naproxen risky at high dose

"Our results suggest that all NSAIDs have harmful effects in heart-failure patients, even naproxen at high doses. Naproxen is probably the best of the bunch, but it still increases fluid retention, which is bad news for heart-failure patients," Gislason added.

But he points out that these drugs are still being used in this population. "I don't think doctors are aware of this problem. We need to raise awareness. I think the main culprits are primary-care doctors, as these drugs are so widely prescribed in general practice," he commented. "The fact that some of these drugs are available over the counter makes the situation much worse, as anyone can buy them without advice from a doctor. All NSAIDs should be prescription-only drugs. Making them available in petrol stations and supermarkets gives the impression that they are not harmful. Many heart-disease patients will not be aware that they shouldn't take them."

In the current study, Gislason and colleagues used Danish national records of hospitalizations and pharmacy drug dispensing to identify 107 092 patients surviving their first hospitalization due to heart failure between 1995 and 2004 and their subsequent use of NSAIDs.

They found that 36 354 patients (33.9%) claimed at least one prescription of an NSAID after discharge; 60 974 patients (56.9%) died, and 8970 (8.4%) and 39 984 (37.5%) were rehospitalized with MI or heart failure.

After adjustment for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, the authors found a clear dose-related increase in risk with the drugs.