Parker Waichman is investigating potential lawsuits on behalf of individuals who suffered injuries related to NSAIDs, including ibuprofen, one of the most popular over-the-counter (OTC) pain relievers used worldwide. According to the Atlanta Journal-Constitution (AJC.com), researchers have long warned against the risk of heart attack and stroke associated with ibuprofen.

Study: NSAIDs may be Unsafe for Arthritis Patients Diagnosed with Cardiovascular Risk

The NSAID, ibuprofen (sold under the brand name Advil), has been associated with increased blood pressure and hypertension risks when compared to the drug, celecoxib (sold under the brand name Celebrex), in patients diagnosed with osteoarthritis or rheumatoid arthritis and who are also at an increased risk of cardiovascular disease, according to results from the PRECISION-ABPM study in a Hot Line Session at ESC Congress on August 28, 2017 and published in EHJ, News-Medical.net.

Nonsteroidal anti-inflammatory drugs and both non-selective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most broadly prescribed drugs around the world; however, the popular medications are tied to increased blood pressure and adverse cardiovascular events. In fact, 19 percent of the United States population uses at least one NSAID medication on a regular basis. This includes 30 million Americans who have been diagnosed with osteoarthritis. Of these individuals, more than 40 percent are also diagnosed with hypertension (abnormally high blood pressure), News-Medical.net wrote.

NSAID labels include warnings concerning the potential increases in blood pressure; however, there is minimal data on the effects of individual drugs, notes News-Medical.net. More than 70,000 deaths occur from stroke and 60,000 deaths occur from coronary heart disease each year; therefore, maintaining or achieving blood pressure control in patients who are diagnosed with arthritis and concomitant hypertension it critical as is additional research into the effects of various NSAID medications on blood pressure.

PRECISION-ABPM, which is a pre-specified four-month sub-study of the landmark PRECISION trial, was designed to determine the blood pressure effects of the selective COX-2 inhibitor celecoxib when compared to the non-selective NSAIDs naproxen and ibuprofen, according to News-Medical.net. PRECISION-ABPM was a prospective, double blind, randomized, non-inferiority cardiovascular safety trial that was conducted at 60 sites in the United States. The research included 444 patients. Of these patients, 408 (92 percent) were diagnosed with osteoarthritis and 36 (eight percent) were diagnosed with rheumatoid arthritis. All of the patients had evidence of, or were at a greater risk for, coronary artery disease.

Patients were randomized in a 1:1:1 manner to receive celecoxib at 100-200 mg twice a day, ibuprofen at 600-800 mg three times a day, or naproxen at 375-500 mg twice a day with matching placebo participants. The study’s primary endpoint was the change from the baseline in 24-hour ambulatory blood pressure following the four-month study period, according to News-Medical.net.

The researchers discovered that celecoxib decreased the average systolic blood pressure level measured over 24 hours by -0.3 mmHg. Ibuprofen and naproxen increased the average systolic blood pressure level by 3.7 and 1.6 mmHg, respectively. The resulting difference of -3.9 mmHg seen between celecoxib and ibuprofen was described by the researchers as significant (p=0.009).

The principal investigator, Professor Frank Ruschitzka, professor of cardiology and co-head of the Department of Cardiology, University Heart Centre, Zurich, Switzerland, said: “PRECISION-ABPM showed differential blood pressure effects between the different NSAIDs, ibuprofen and naproxen, and the COX-2 inhibitor celecoxib. While celecoxib and naproxen produced either a slight decrease (celecoxib) or a relatively small increase (naproxen) in blood pressure, ibuprofen was associated with a significant increase in ambulatory systolic blood pressure of more than 3 mmHg” News-Medical.net reported.

An additional analysis revealed that the percentage of patients diagnosed with normal baseline blood pressure who also developed hypertension was 23.2 percent for ibuprofen, 19.0 percent for naproxen, and 10.3 percent for celecoxib. According to study data, this means there was an odds ratio [OR] of 0.39, p=0.004 and OR 0.49, p=0.03 for celecoxib versus ibuprofen and naproxen, respectively). In other words, “Patients receiving ibuprofen had a 61 percent higher incidence of de novo hypertension compared to those receiving celecoxib,” said Professor Ruschitzka, News-Medical.net reported. “De novo hypertension can be caused by endocrine conditions, obesity, pregnancy, and certain medications,” according to Human Research Roadmap.

The results from this study support and extend the findings from the PRECISION trial, which demonstrated non-inferiority for the primary cardiovascular outcomes involving moderate doses of celecoxib when compared with naproxen or ibuprofen. These findings may have the greatest clinical significance in the elderly population, who tend to have a higher level of arthritis and hypertension. Professor Ruschitzka said that, “The current findings suggest that the elevated cardiovascular risk with NSAIDs may be partly due to drug-specific increases in blood pressure. This challenges the widely advocated belief that conventional NSAIDs, like naproxen and ibuprofen, with their higher COX-1 (and thromboxane reducing) effects would provide greater cardiovascular safety than other more COX-2 selective agents, particularly celecoxib.”

Professor Ruschizka concluded that, “PRECISION-ABPM clearly demonstrates that NSAIDs, particularly ibuprofen, may be not as safe as previously thought. Patients should continue to consult their doctor before taking NSAIDs or coxibs and clinicians need to weigh the potential hazards of worsening blood pressure control when considering the use of these agents,” according to Medicine-News.net.

Danish Study Reveals That NSAIDs Increase Heart Attack Risk

A Danish study published in the March 2017 issue of the European Heart Journal-Cardiovascular Pharmacotherapy found that taking any type of NSAID, including ibuprofen, may increase risks of heart attack by 31 percent. Gunnar H. Gislason, study author and professor of a cardiology, said in a news release that, “Allowing these drugs to be purchased without a prescription, and without any advice or restrictions, sends a message to the public that they must be safe.” He added that, “The findings are a stark reminder that NSAIDs are not harmless.”

According to the study, more than half of all the adult Danish population received at least one NSAID prescription during 1997-2005. Also, in 2010, 29.6 million adults in the United States used an NSAID on a regular basis.

The risk of different events varies depending upon the clinical context, medication, and dosage. Nonselective NSAIDs and cyclooxygenase (COX)-2 selective NSAIDs (coxibs) increase these risks, according to UpToDate.com.

In the last 10 years, evidence of cardiovascular risk tied to the use of NSAIDs has arisen, according to the research. The selective COX-2 inhibitors, and to a lesser extent, the non-selective NSAIDs, have been tied with cardiovascular adverse events. Randomized and observational studies of cardiovascular events included myocardial infarction, stroke, and heart failure. Cardiac arrest was found to be the “ultimate adverse drug event,” and while closely associated with ischemic disease and cardiovascular morbidity, the association between NSAIDs and cardiac arrest had never previously been probed, according to the research.

Also, there is no research concerning NSAIDs pro-arrhythmic effects on ventricular arrhythmias as isolated events; however, an association with NSAIDs and sudden cardiac death as part of a “composite endpoint” with myocardial infarction was observed. Because of this, additional research was found to be needed to establish that NSAIDs use may be associated with cardiac arrest. This prompted the research team to conduct the observational case–time–control study. The researchers used data from the Danish nationwide registries to analyze the association between NSAID use and the risk of out-of-hospital cardiac arrest (OHCA).

The researchers’ primary endpoint was OHCA; a cause of cardiac arrest is not registered in the Danish Cardiac Arrest Registry. The presumed cause of cardiac arrest was classified using discharge diagnoses from The Danish Patient Registry, as well as death certificates from The National Causes of Death Registry. “A presumed cardiac cause of cardiac arrest was defined as an event with diagnosis code covering a known cardiac disease, unknown disease, or unexpected collapse according to the Utstein template.” Other medical conditions, trauma, drug overdose, attempted suicide, and violent attack were considered non-cardiac causes. “Cardiac arrest of presumed cardiac cause represented about 75 percent of all OHCA recorded in the Danish Cardiac Arrest Registry during 2001–10.” The Utstein template is a set of guidelines for uniform reporting of cardiac arrest. The European Society of Cardiology noted that the researchers used the Danish Cardiac Arrest Registry to collect the medical history of approximately 30,000 patients who suffered a heart attack outside of the hospital from 2000 to 2010. The team also reviewed all NSAID prescriptions filled at Danish pharmacies since 1995.

The researchers concluded that, “In a nationwide cohort of persons with OHCA, we found that short-term treatment with non-selective NSAIDs, particularly ibuprofen and diclofenac, was associated with an increased early risk of cardiac arrest. We found no association between cardiac arrest and use of the COX-2 selective inhibitors, rofecoxib and celecoxib, nor the non-selective NSAID naproxen. Our findings support the accumulating evidence of an unfavorable cardiovascular risk profile associated with use of the non-selective NSAIDs. This calls for special awareness in order to balance risks against benefits in treatment with NSAIDs.

According to The European Society of Cardiology, Professor Gislason said “I don’t think these drugs should be sold in supermarkets or petrol stations where there is no professional advice on how to use them. Over-the-counter NSAIDs should only be available at pharmacies, in limited quantities, and in low doses.” He added, “Do not take more than 1200 mg of ibuprofen per day,” noting that “Naproxen is probably the safest NSAID and we can take up to 500 mg a day. Diclofenac is the riskiest NSAID and should be avoided by patients with cardiovascular disease and the general population. Safer drugs are available that have similar painkilling effects so there is no reason to use diclofenac.”

Professor Gislason concluded: “The current message being sent to the public about NSAIDs is wrong. If you can buy these drugs in a convenience store then you probably think ‘they must be safe for me.’ Our study adds to the evidence about the adverse cardiovascular effects of NSAIDs and confirms that they should be taken seriously, and used only after consulting a healthcare professional.”

According to Time, ibuprofen, which is sold under the brand name Advil, and naproxen, which is sold under the brand name Aleve, are both available over the counter in the United States but require prescriptions in Denmark. The only NSAID sold without a prescription in that country is ibuprofen in 200mg, which corresponds to regular-strength Advil in the United States. Diclofenec requires a prescription in Denmark and the United States.

Diclofenac and ibuprofen were found to be the most popularly used NSAIDs seen in heart attack cases, the study found. In fact, diclofenac and prescription-strength ibuprofen contributed 50 percent and 31 percent of the increased risk for cardiac arrest, respectively.

In addition to Gislason warning that NSAIDs should be used with caution, he offered a number of tips:

• Avoid taking NSAIDs if you have cardiovascular disease or many cardiovascular risk factors.
• Do not take more than 1,200 mg. per day of ibuprofen.
• Do not buy NSAIDs in locations where there is no professional advice available.
• Naproxen is “probably the safest NSAID” and patients may take up to 500 mg a day.
• Diclofenac is “the riskiest NSAID” and should be avoided by patients diagnosed with cardiovascular disease and the general population. Choose other safer drugs with similar painkilling effects.

The European Society of Cardiology reported that NSAIDs lead to a number of adverse effects on the cardiovascular system, which may explain the association with cardiac arrest, including influencing platelet aggregation and causing blood clots, causing the arteries to constrict, increasing fluid retention, and raising blood pressure.

The study’s results confirm what is already known about NSAIDs, which is that they may lead to sodium retention and making blood thicker and stickier, which creates a “small but finite risk” for cardiovascular events, said Dr. Christopher O’Connor, editor-in-chief of the American College of Cardiology journal JACC-Heart Failure. “I would say the message here is to be careful taking nonsteroidals, particularly high doses, and particularly if you have a preexisting cardiovascular disease,” Dr. O’Connor said.

Legal Help for Individuals Injured by NSAIDs

If you or someone you know has suffered injuries from NSAIDs, you may have valuable legal rights. Contact Parker Waichman LLP today for a free, no-obligation case evaluation. For more information, fill out our online form or call one of our experienced attorneys today at 1-800-YOURLAWYER (1-800-968-7529).