Common Painkillers Lead To Heart Failure

The BMJ has issued a press release on a study stating that common prescription painkillers increase the risk of heart disease. The drugs include traditional non-steroidal anti-inflammatory drugs (NSAIDs) as well as new breed of anti-inflammatory drugs, known as COX-2 inhibitors. COX-2 inhibitors are a type of NSAIDs that directly attack cyclooxygenase-2 or COX-2 enzyme responsible for pain and inflammation.

Current use of any NSAIDs, which was calculated as use in preceding 14 days, was found to be associated with a 19% increase of risk of hospital admission for heart failure compared with past use of NSAIDs, which was set as use greater than 183 days old.

Studies have shown an association between use of traditional NSAIDs and COX 2 inhibitors and an increased risk of heart failure, but the risk and dose-response relation associated with individual drugs is still largely a mystery.

The team of researchers, led by Giovanni Corrao at the University of Milano-Bicocca in Italy, wanted to investigate the risk of hospital admission for heart failure with the use of individual NSAIDs.

Their research is based on approximately 10 million NSAIDs users from four European countries including the United Kingdom, the Netherlands, Germany and Italy. The study included 27 different NSAIDS and 4 different COX 2 inhibitors.

A total of 92,163 hospital admissions for heart failure were identified in adult patients aged 18 and older, and matched with 8,246,403 control patients. The mean age was 77 and 76 among case and control participants respectively, where 55% of the total population including case and control was female.

The researchers concluded that current use of NSAIDS were linked with higher hospital admission risk for heart failure, compared to NSAIDS use in the past.

The researchers further added that the risk of admission for heart failure increased for seven commonly used NSAIDs and two COX2 inhibitors, after they had accounted for potential confounders. The seven commonly used NSAIDS were: diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam and two COX 2 inhibitors: etoricoxib and rofecoxib.

The researchers further noted that the enormity of risk varied between individual NSAIDs and the dose prescribed. At extremely high drug doses, risk of admission for heart failure doubled for some NSAIDs.

There was however no evidence that celecoxib was related to an increased risk of admission for heart failure at normal commonly used doses. However, celecoxib was used mostly in low doses because of which the safety of celecoxib at higher doses still needs to be figured out.

There were limitations to the study. Some diseases that change both the risk of heart failure and probability of current NSAIDs use might not have been fully taken into consideration in the study. Some individual NSAIDs, more frequently used for different acute or chronic conditions could, have resulted in different use behaviors as well as in different types of populations of users. Hence the researchers had to adjust for the different conditions including osteoarthritis, rheumatoid arthritis and inflammatory polyarthritis.

Since the drugs are so easily available over the counter in all four countries, patients categorized as non-current users of NSAIDs in the study might actually have been current users of over the counter NSAIDs, which could have undermined the actual association between use of individual NSAIDs and heart failure risk.

Relative risk estimates for individual NSAIDs among patients with prior outpatient or secondary hospital diagnoses of heart failure did not seem to differ significantly from the risk calculated in the overall analysis.

This is an observational study, so no conclusive evaluation can be made about cause and effect, and information on absolute risks was not made available to the researchers.

Despite these minor setbacks, the authors said that their study “offers further evidence that the most frequently used individual traditional NSAIDs and selective COX 2 inhibitors are associated with an increased risk of hospital admission for heart failure. Moreover, the risk seems to vary between drugs and according to the dose”.

The researchers concluded: “Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practices and regulatory activities.”

Owing to the widespread use of NSAIDs, even if there is a tiny increase in cardiovascular disease risk, it is an alarming situation for the sake of public health, according to two Danish heart experts’ statements made in a related editorial.

They further went on to say that due to the wide availability over the counter in supermarkets and convenience stores, it further adds the risk since they are so easily available.

They wrote that the wide availability of these drugs “further fuels the common misconception that NSAIDs are harmless drugs that are safe for everyone”. They added that stricter regulations are needed and “requirements for healthcare professionals providing advice on their use and potential harm is warranted”.

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