Many Guidelines, Mixed Consensus: Different CVD Risk Guidelines Cause Confusion in Practice

A new review has identified more than 20 clinical guidelines for cardiovascular risk assessment, noting there are considerable discrepancies between the different recommendations, particularly when it comes to the optimum screening strategy and the threshold for initiating treatment.

Overall, there was no consensus on the ideal target population, with US and Canadian guidelines for the assessment of cardiovascular risk, as well as those for dyslipidemia and hypertension, advocating screening in younger patients compared with the European, United Kingdom, and Australian guidelines.

The net result, according to senior investigator Myriam Hunink, MD (Erasmus Medical Center, Rotterdam, the Netherlands), is “confusion” for the practicing physician. That said, the different clinical guidelines are designed for different countries with different healthcare systems so the discrepant recommendations make sense on one level. “To some extent, it is logical and explainable,” she told TCTMD. “But on the other hand, it calls up questions, since it’s all based on the same evidence base. So why does it result it different recommendations?”

For example, of the five clinical guidelines for total cardiovascular disease risk assessment—which include recommendations from the European Society of Cardiology (ESC), the National Institute for Health and Care Excellence (NICE), the National Vascular Disease Prevention Alliance, the American College of Cardiology/American Heart Association (ACC/AHA), and the Centers for Disease Control and Prevention (CDC)—there are different thresholds for initiating statin therapy.

The ACC/AHA clinical guidelines recommend starting statin therapy in individuals who lack evidence of cardiovascular disease or diabetes but who have LDL-cholesterol levels between 70 and 189 mg/dL and a 10-year risk of atherosclerotic cardiovascular disease ≥ 7.5%. In contrast, the ESC and NICE propose starting therapy in patients with a 10-year risk of cardiovascular disease ≥ 10%, while the CDC recommends starting treatment in those with a 10-year risk exceeding 20%.

Sekar Kathiresan, MD (Massachusetts General Hospital, Boston, MA), who wasn’t involved in the study, told TCTMD he wasn’t particularly surprised by disparate recommendations, noting there are numerous organizations, each with a slightly different constituency and focus.

In a way, lumping in various clinical guidelines from the different organizations with different focal points creates an “artificial heterogeneity,” he said. Even among organizations with a similar focus and constituency, Kathiresan believes there will always be some degree of variability, but that for the most part there is a “general” consensus on cardiovascular risk assessment and treatment.

In the United States, the dominant clinical guidelines for the assessment of cardiovascular risk are the ACC/AHA recommendations, he noted, while in Europe the ESC is the go-to source.

“I think there’s a lot of guidelines, and they say different things,” said Kathiresan. “What does that mean? Is the expectation that there should only be one guideline, or one [message] to emerge from all the guidelines? I don’t think so. There are some legitimate issues, such as the best way to assess risk and what threshold should be used to assign treatment. Those are important questions, but I think there’s general consensus among those things. There’s some differences in the margins, but everybody generally agrees on the set of risk factors to assess risk and generally agrees on thresholds for statin and aspirin use.”

Results of the study were published online September 13, 2016, ahead of print in the Annals of Internal Medicine.

Confusion for Practicing Physician

In their review of the guidelines, Hunink and colleagues note that recommendations on when to start antihypertensive medication vary across the different groups, with no consensus on blood-pressure thresholds, as well as no agreement among clinical guidelines on which screening test should be used to detect subclinical atherosclerosis. The ESC and ACC/AHA recommend using coronary artery calcium (CAC) scoring and carotid ultrasound for the detection of atherosclerosis, but only in selected individuals. The Australia-based National Vascular Disease Prevention Alliance is the only group to recommend the assessment of left ventricular hypertrophy in primary-risk assessment.

Hunink noted that the discrepant recommendations could lead to inequalities in care across regions and countries. Even within the same country, the various regulatory bodies often make different recommendations. For example, in 2013 the American Association of Clinical Endocrinologists (AACE) publicly rejected the ACC/AHA cholesterol guidelines, arguing the ACC/AHA recommendations did not line up with their own ideas for screening and management. Specifically, they disagreed with removal of the LDL targets and the idea that statin therapy alone is sufficient for all at-risk patients.

To TCTMD, Hunink said the researchers are uncertain why the clinical guidelines they analyzed—including the five guidelines for the assessment of total cardiovascular risk, two guidelines focusing on screening for dyslipidemia, seven guidelines on screening for diabetes, and three screening for hypertension—differ to such an extent. The bottom line is that researchers and experts are interpreting the data somewhat differently and reaching different conclusions, she said.

“All of the guidelines seem to agree that you should screen for cardiovascular risk, but the disagreements are more in the area of what strategy to choose, which risk score you should use, such as the EuroSCORE, the ACC/AHA risk calculator, or the Framingham risk score,” said Hunink. “There are also disagreements on the target population, as well as the age in which to start screening and the treatment threshold.”

Steven Nissen, MD (Cleveland Clinic, OH), who was not involved in the analysis, agreed with the conclusions of the researchers, saying the study raises a very important point, namely that physicians around the world can view the same evidence yet make very different conclusions. “It’s very confusing for physicians, for patients, and it’s a huge problem,” he told TCTMD. “It really does show that we have a long way to go in terms of the guideline process.”

The present study, and the differing recommendations, suggest that the guidelines are based to a large extent on expert opinion, he added.

For Nissen, who has admittedly been critical of the US guidelines, specifically the recommendations for the treatment of cholesterol, the study highlights the fact that many other organizations, such as the ESC, don’t agree with the recent ACC/AHA guidelines. He noted the 2013 decision to abandon lipid targets was not followed by other organizations, which emphasizes the need for a “better global process for coming together for these types of guidelines.”

To rectify the guideline-writing process, Nissen believes an open commenting period would allow opportunities for other physicians and researchers to voice their opinion about proposed recommendations. For example, when the United States Preventive Services Task Force (USPSTF) is in the process of drafting recommendations, including those on the use of statin therapy, there is an opportunity for public comment. Such transparency can help limit some of the discrepant advice from differing organizations. “I think it would help a lot because there would be dialogue,” said Nissen. 

Regarding areas of agreement, Hunink and colleagues found multiple guidelines supporting cardiovascular disease risk assessment, with a consensus that selective screening should be based on patient characteristics. The guidelines recommend integrating age, sex, smoking, blood pressure, and lipid levels into risk-prediction models, but there was no consensus on which risk-prediction model to use. There was agreement that the use of novel biomarkers, such as C-reactive protein (CRP) and apolipoproteins, should be limited. Screening intervals ranged from 2 to 6 years, and there was widespread agreement that physicians should address lifestyle factors in all patients independent of drug therapy.

Consensus on Aspirin Use: It’s a No in Primary Prevention

Of the five clinical guidelines for total cardiovascular risk assessment, the ESC and National Vascular Disease Prevention Alliance do not recommend aspirin for primary prevention, while the CDC guidelines state aspirin might be useful in women 65 years and older. NICE and the ACC/AHA make no reference to aspirin use in primary prevention, while several guidelines for the treatment of impaired glucose levels recommend aspirin in high-risk patients with additional cardiovascular risk factors.

“At the very least, physicians should be aware of the differences between the guidelines and really try to come to an understanding to see what fits within their particularly context,” said Hunink. “They should really try to see what patient population the guidelines are talking about and what tests they’re recommending, and see if that fits within the healthcare system they’re working in.”

The multiple guidelines and recommendations provide a degree of flexibility for physicians, she added, noting that physicians do not need to feel boxed in if the recommendations for a particular patient don’t apply. They can consider the guidelines one of many, seeking out differing documents for a better fit for treatment, if needed.

Related Stories:

• Focus on LDL Cholesterol Targets with Statin Therapy, New ESC-EAS Cholesterol Guidelines Say
• The EU Versus US Lipid Guideline Debate: It’s the Gap that Matters, Experts Say
• ACC Updates LDL-Cholesterol Lowering Recommendations, Making Room for Ezetimibe and PCSK9 Inhibitors