The more patients who adhere to the prescribed statin regimen, the lower the mortality, although they were selected for the retrospective study because they are not new to statin therapy. The entry criteria were also designed to minimize the effect of poor statin adherence due to perceived adverse effects.
The more than 340,000 patients with atherosclerotic cardiovascular disease (ASCVD) in a Veterans Affairs cohort were selected for on-going statin prescriptions without change in treatment intensity.
This resulted in a cohort in which the average follow-up of statin therapy was about 87%, which holds clinical practice high, and yet they still showed a dose-response relationship between attachment and over a period of about three years Mortality, Fatima Rodriguez, MD, MPH, Stanford University, California, told theheart.org | Medscape cardiology,
"We were surprised at how strong the adherence was even with this high degree of adherence, and there was still this graduated relationship."
This is especially true for patients who are prescribed high-intensity statins compared to moderate or low-intensity statin therapy, said Rodriguez, the lead author of the February 13 analysis JAMA Cardiology,
"Even for patients who seem to be moderately affectionate, there is still an advantage in being in the highest compliance category and taking all medications."
Such inverse relationships between statin adhesion and clinical outcomes have long been observed, but "much of the work done in this area has focused on people receiving a prescription immediately after an event," said Rodriguez.
"And we know that their compliance is very low, less than 50%, usually after a year, even though they are at a very high risk."
The current patients, who have been treated on an outpatient basis, including continued statins in stable doses, are likely to be less likely than statin recipients in the general practice to avoid taking their prescribed statins due to perceived muscle pain or discomfort or other side effects.
Nevertheless, the inverse relationship between statin adherence and mortality is "not unexpected," writes dr. Ann Marie Navar, PhD of the Duke Clinical Research Institute, Durham, North Carolina, in an accompanying editorial.
"The novelty of this study is the authors' comprehensive attempt to understand whether the link between statins and mortality is due to the drug itself and the preference for 'healthy followers', where adherence is a marker of improved self-care and healthy behavior is, "says the editorial.
A high degree of adherence even to placebo "is in fact associated with improved outcomes after myocardial infarction and lower cardiovascular mortality, and it is possible that low adherence patients are likely to have adverse health behaviors, such as smoking, or poor psychosocial support" , the report admits.
"We tried to explain that patients who take medication are different from those who do not take medication," said Rodriguez. Mortality analysis was adjusted for baseline features such as blood pressure, but also for compliance with ACE inhibitors, beta-blockers and other cardiovascular drugs.
"It has mitigated the results, but not changed," she said. Statin adherence was still significantly associated with survival in a dose-response manner.
Second, in the editorial notes, the researchers found no significant association between hospitalizations for pneumonia or gastrointestinal bleeding, which served as control of mortality.
"The adherence-mortality association was strongest among those who were given high-intensity statins and the lowest statins in the prescribed low-intensity statins," Navar writes.
"These three results show that the mortality benefit in this study is not just due to a healthy follower."
"Looking for signs of disagreement"
The analysis confirms an effect observed in other studies with different populations, Neil J. Stone, MD, Northwestern University, Chicago, agreed in an interview.
He praised the effort to focus on patients who already tolerated statins and to minimize the impact of healthy adherents.
"However, at the end of the day, it's just an observational study supporting a number of other observational studies," said Stone, co-author of the American Heart Association and the 2018 American College of Cardiology Guideline on Blood Cholesterol. "Here you have confirmation in the VA population."
There is evidence that about two-thirds of doctors do not know if their patients are taking their prescribed medications, Stone observed. "I would say, number one, look for signs of non-attachment, because it can be more common than you think, when you ask the question," How many pills have you missed in the last 30 days? "Is much better than" Take yours. "Medicines."
He also said guidelines have long recommended lipid panel follow-ups after a patient had begun with statin therapy, "both in terms of adherence and adequacy of effect."
If the adherence is not good, "it is worthwhile for the patient and the doctor to find out what's going on and to see if they can put on the patient, if not the same statin, another statin."
Liability may also decline over time, suggesting the need for continuous follow-up. "Sometimes, when you have a medicine that has been on board for some time, we just assume that you are taking it," Rodriguez noted.
High adhesion overall
The study included 347,104 adults aged up to 85 years with ASCVD for at least two evaluations within the previous 2 years who were prescribed statin therapy without intensity adjustment. They were treated in the Veterans Affairs Health System for a period of 16 months in 2013 and 2014.
Researchers defined statin use as a filled prescription for one of the medications over the last 6 months; Patients with new statin prescriptions had been excluded.
Statin adherence, defined in accordance with the drug possession rate (MPR), was the ratio of outpatient days given a prescribed daily statin dose to live off-hospital days over 12 months.
At an absolute definition of at least 80% MPR, 87.7% of the cohort was subject to prescribed statin therapy. But about 85% of the cohort had an MPR of at least 70% and more than 63% had an MPR of at least 90%.
Not surprisingly, the low density cholesterol (lipoprotein lipoprotein) (LDL-C) continued to decrease with increasing statin adherence, and in patients with an MPR of less than 50% to 92.1 mg / dl and in patients with an MPR of at least 90 at 77.2 mg / dL% (P <.001 for trend).
A similar relationship was seen for adjusted all-cause mortality, the primary endpoint. The absolute mortality averaged 24.8% over an average follow-up period of 2.9 years.
|Results by MPR level, compared to MPR ≥90%|
|MPR||Mortality rate (95% CI)||IHD or ischemic stroke rate (95% CI)|
|<50%||1.30 (1.27-1.34)||1.08 (1.03-1.14)|
|50% to 69%||1.21 (1.18-1.24)||1.02 (0.99-1.07)|
|70% to 89%||1.08 (1.06-1.09)||1.09 (1.06-1.12)|
|IHD = ischemic heart disease.
Adjusted for baseline characteristics, including compliance with ACE inhibitors and beta-blockers, age, statin intensity, gender, race or ethnicity, ASCVD diagnosis, concomitant diseases, teaching hospital or not, creatinine, vital signs, pulse oximetry and weight.
"This effect is most pronounced for patients with high-intensity statins, especially in the VA, the most risky patients are likely to be on high-intensity statins, which is appropriate, and I think we see the effect amplified for these patients," Rodriguez said.
"Not only do you want your patients to be adherent, but they also want to stick to the statin with the highest intensity they can possibly tolerate, because the benefit of a high-intensity statin is high compared to a statin high But a low-intensity statin is better than zero statins. "
|Statin intensity * mortality risk ratio * by MPR level, compared to MPR ≥90%|
|MPR||High, 25% (95% CI)||Moderate, 63% (95% CI)||Low, 12% (95% CI)|
|<50%||1.35 (1.27-1.43)||1.32 (1.27-1.36)||1.21 (1.13-1.29)|
|50% to 69%||1.23 (1.17-1.30)||1.21 (1.17-1.24)||1.18 (1.11-1.25)|
|70% to 89%||1.10 (1.06-1.14)||1.07 (1.05-1.10)||1.04 (1.00-1.09)|
|Adjusted for baseline characteristics, including compliance with other cardiac medications, age, statin intensity, gender, race or ethnicity, ASCVD diagnosis, comorbidities, hospital status, creatinine, vital signs, pulse oximetry, and weight.
* Statin Intensity: High = atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg. Moderate = Atorvastatin 10 to 20 mg; Fluvastatin 40 mg twice daily or 80 mg once daily; Lovastatin 40 mg; Pitavastatin 2 to 4 mg; Pravastatin 40 to 80 mg; Rosuvastatin 5 to 10 mg; Simvastatin 20 to 40 mg. Low = fluvastatin 20 to 40 mg; Lovastatin 20 mg; Simvastatin 10 mg; Pitavastatin 1 mg; Pravastatin 10 to 20 mg.
Rodriguez has not reported any conflicts. The information for the other authors is included in the report. Navar claims to receive grants and personal fees from Amarin, Amgen, Regeneron and Sanofi; Fees of NovoNordisk and AstraZeneca; and grants from Janssen. Stone did not report conflicts.
JAMA Cardiology, Published February 13, 2019. Report, Editorial