A new multinational study shows that the most popular treatment for first-line hypertension is less effective and has more side effects than an alternative that is prescribed much less frequently.
Researchers, including George Hripsack in Columbia and Dr. Patrick Ryan, analyzed electronic health records and claimed data from nearly 5 million patients who started treatment with hypertension medications. They found that patients who were first prescribed thiazide diuretics had 1
Researchers estimate that approximately 3,100 major cardiovascular events among patients who were the first to take ACE inhibitors could be avoided if they were first treated with a thiazide diuretic.
– the most comprehensive comparison of results in newly treated patients with hypertension – was published in Lancet .
Little evidence for drug selection
Current guidelines from the American College of Cardiology and the American Heart Association recommend that antihypertensive therapy be initiated with each drug of five different drug classes, including thiazide diuretics , angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers.  But there is little evidence to help physicians decide which class of medication to start with: li therapy contains data from randomized, controlled clinical trials involving only 31,000 patients – and none have started antihypertensive treatment. As a result, most clinical guidelines are based on expertise, not data.
"Randomized clinical trials demonstrate the efficacy and safety of the drug in a highly defined patient population," says George Hripsack, MD, chairman of the University of Columbia's Vagelos College of Physicians and Surgeons and author of the study. "But they are not good at comparing multiple classes of drugs to the diverse group of patients you would encounter in the real world."
Observational studies may be used to detect effects that may not have been apparent in randomized trials. But many are too small to make meaningful conclusions or suffer from other types of distortions.
"Unwittingly or not, journals and authors tend to publish studies that have exciting results, and researchers can even choose the analytical methods that are best suited to obtain results that fit their hypotheses," says Chrysak. "It comes down to a cherry picking exercise that makes the results less reliable."
Read this article to learn more about surveillance biases.
Solution: Big data
To address these limitations, researchers analyze data from millions of patients' health records and account for tens of thousands of different variables – critical for eliminating confusing factors. The method, known as Generating and Evaluating Large-Scale Evidence in a Database Network, or LEGEND, was created by a consortium of scientists participating in the Health Data Observation Network (OHDSI, pronounced "odyssey"). Using LEGEND, researchers are able to share their methodology and standardize data while minimizing bias.
"LEGEND provides a systematic framework that can generate evidence reproducibly by applying advanced analysis to a network of different databases for a wide range of exposures and results," says Patrick Ryan, MD, Assistant Professor of Biomedical Informatics at Columbia University Vagelos College of Physicians and Surgeons and Vice President of Data Health Monitoring, Janssen Research and Development. "Not only does LEGEND provide a way to scale the real needs of the healthcare community, but it also provides additional diagnostics to help us understand how much we can trust the evidence we provide."
This study analyzes insurance claims and electronic health records from 4.9 million patients in four countries who are starting single-drug antihypertensive therapy. The researchers used a sophisticated algorithm to identify the number of heart attacks, hospitalizations for heart failure, strokes, and nearly 50 side effects in patients taking any of the first line antihypertensive drugs. They have also used a number of techniques designed to minimize bias and account for about 60,000 different variables.
The study found that ACE inhibitors were the first antihypertensive drug prescribed in 48% of patients, compared with 17% of patients who were first prescribed thiazide diuretics. However, patients who were first treated with thiazide diuretics had 15% less heart attacks, hospitalizations for heart failure, and strokes than those treated with other first-line therapies. In addition, patients treated for the first time with ACE inhibitors have a higher rate of 19 side effects compared to thiazide users.
The study also found that non-dihydropyridine calcium channel blockers were less effective than all other first-line drugs.  "With LEGEND, we have found a way to fill the gaps left by randomized, controlled trials and to help guide physicians in clinical decision making," says Hripcsak.
The paper, "Comprehensive Comparative Efficacy and Safety First, Linear Classes of Antihypertensive Drugs: A Systematic, Multinational, Large-Scale Analysis," was published in The Lancet .
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Columbia University Irving Medical Center
Most prescribed blood pressure medications may be less effective than others (2019, October 24)
retrieved October 25, 2019
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