CV Events, Death Lower After Statin Rechallenge

Patrice Wendling

July 26, 2017

BEIJING, CHINA — New research shows that nearly 30% of patients did not receive a statin prescription after an adverse reaction, but those who continued on therapy had a 10% to 20% lower risk of cardiovascular events and death[1].

In multivariable analysis, continued statin therapy was associated with hazard ratios of 0.87 (P<0.001) for the composite primary end point of MI, stroke, and all-cause death; 0.79 (P<0.001) for death; and 0.92 (P=0.054) for CV events.

"We are providing evidence that it may be worthwhile to try a statin again," senior author Dr Alexander Turchin (Brigham and Women's Hospital, Boston MA) told | Medscape Cardiology.

Although randomized trials have shown similar benefits, he said, "We didn't think that the outcome of this analysis was preordained, because if patients actually had a high rate of recurrent adverse reactions that were intolerable, even if they tried a statin again they wouldn't be continuing it and experiencing any benefits."

The fact that they found benefit in resuming treatment, he added, "is evidence that patients are able to continue to tolerate statins and get these benefits, and that's why it's worthwhile to try again."

In this analysis of 28,266 adults who had at least one adverse reaction to a statin, 8277 did not continue statin therapy.

In an accompanying editorial[2], Dr Steven Nissen (Cleveland Clinic, OH) rails against the deadly consequences of the "statin-denial cult" and the proliferation of websites developed by "people with little or no scientific expertise, who often peddle 'natural' or 'drug-free' remedies for elevated cholesterol levels."

"It's what happened to us with the antivaxers," Nissen said in an interview. "The antivaxers somehow got the public's attention and they created a cult and people wanted to believe it. It's like the whole fake news thing that has come to the fore."

He added, "Physicians and physician scientists have to stand tall for scientific truth, and we can't be passive. Really my editorial, among other things, is a call to action."

Dr Rita Redberg (University of California, San Francisco), a vocal proponent of shifting the emphasis from cholesterol to healthy lifestyle measures to reduce CV risk, said in an email, "This study provides additional evidence to support the frequent complaints I hear from many of my patients taking statins about adverse effects."

She said the investigators and editorialist rightly point out that "one cannot rely on outcomes from observational data" and that "as Nissen notes, 'Most thoughtful observers consider the reliability of epidemiologic research low unless the observed odds ratio or relative risk is less than 0.5.' The hazard ratio in this epi study is 0.87."

"Furthermore," Redberg said, "We know that people who take their medicines do better than people who do not take their medicines related to other characteristics and nothing to do with the actual medicines."

The study was published July 25, 2017 in the Annals of Internal Medicine.

Statin Intolerance

The investigators used a combination of electronic medical record coding and natural-language processing of chart notes to identify 28,266 adults receiving statin prescriptions between 2000 and 2011 who had at least one adverse reaction presumed due to the statin. Myalgia (24.6%) and other musculoskeletal complaints (17.8%) were the most common reactions.

After a mean of 4.4 years follow-up, the composite primary end point occurred in 12.2% of patients with and 13.9% of patients without continued statin prescriptions (P<0.001). Death was reduced 1.2% (5.4% vs 6.6%; P<0.001) and CV events 0.9% (7.6% vs 8.5%; P=0.024).

Notably, those with continued statin prescriptions were older; more likely to have a personal or family history of coronary artery disease, diabetes, or obesity; and to be evaluated by a cardiologist.

"Provider specialty seemed to play as strong a role as the patient's risk factors," the authors write.

A 2015 Danish study also found an increased risk of MI and death in patients who stopped statins early on and reported that statin noncompliance increases when negative stories about statins dominate the media.

At that time, Nissen urged restraint in how the media report stories generated by "antistatin zealots" and called on the major cardiology societies to take the lead in educating patients about statin benefits and safety.

Nissen doubled down on that message with the new results but added, "I don't think the professional societies have done enough to educate the public about the importance of statin adherence. We can do better, but it will require the willingness of professional societies to directly engage the public, not just their physician and nurse membership."

A Second Statin

In a secondary analysis of patients prescribed a different statin after the first adverse reaction, the primary end point occurred in 11.9% vs 14.5% who did not continue receiving statins.

The authors note that 26.5% of patients had a recurrent adverse reaction to the second statin but that 84.2% of those continued receiving statins, "suggesting that the symptoms were mild or tolerable. Both the absolute risk and symptom severity must be weighed against the potential benefits of continuing statin therapy after a presumed adverse event."

Because the study enrolled largely high-risk patients with a 10-year combined CV event and death rate of more than 20%, or well above the >7.5% CV risk threshold for statins in the recent guidelines, the authors say future studies are needed "to establish the cardiovascular risk threshold below which a statin rechallenge after an adverse reaction may be more harmful than beneficial for the patient."

Redberg remarked, "Weighing risks and benefits, the best strategy for reducing CV risk in primary prevention remains a healthy diet, regular physical activity, and not smoking. For patients with established heart disease, there is a benefit to statins in addition to lifestyle measures and other medical therapies."

The study was funded by grants from the Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College Hospital. Turchin reported grants from Sanofi and Merck. Disclosures for the coauthors are listed in the paper. Nissen reported grants from Esperion Therapeutics during the conduct of the study and grants from Amgen, Pfizer, and AstraZeneca outside the submitted work. Redberg has no relevant financial relationships.

Follow Patrice Wendling on Twitter: @pwendl. For more from | Medscape Cardiology, follow us on Twitter and Facebook.


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