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Grand Rounds

Results from the LEGEND-HTN study: Is There a Preferred First-Line Medication to Treat Hypertension?

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BACKGROUND AND PURPOSE:

  • ACC/AHA and other professional bodies recommend a list of medications that can be considered ‘first-line’ in the treatment of hypertension (see ‘Related ObG Topics’ below)
  • Five classes of first-line BP medications include
    • Thiazide or thiazide-like diuretics | Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or calcium channel blockers
  • Suchard et al. (Lancet, 2019) compared these medications to assess comparative effectiveness, safety and related outcomes

METHODS:

  • Systematic, large-scale cohort study
    • Observational data from millions of patients
    • Ability to adjust for confounding, publication bias and manipulation of statistical significance parameters (‘P-hacking’)
  • Study design and data analysis
    • Comprehensive framework for real-world evidence
    • Compared all first-line classes across a global network of six administrative claims and three electronic health record databases
  • Primary outcomes
    • Acute myocardial infarction
    • Hospitalization for heart failure
    • Stroke
  • Secondary outcomes
    • Effectiveness outcomes
    • Safety outcomes

RESULTS:

  • Data from 4.9 million patients initiating monotherapy for elevated BP were included
    • 22,000 calibrated, propensity score adjusted hazard ratios (HRs) were generated
  • The majority of these comparisons did not show any effectiveness differences between the different drug classes
  • However, thiazide or thiazide-like diuretics showed better primary effectiveness than ACE inhibitors for the following
    • Acute myocardial infarction: HR 0.84 (95% CI, 0.75 to 0.95)
    • Hospitalization for heart failure: HR 0.83 (95% CI, 0.74 to 0.95)
    • Stroke: 0.83 (95% CI, 0.74 to 0.95)
  • Safety profiles
    • Thiazide or thiazide-like diuretics demonstrated better safety profiles for significant adverse events compared to ACE inhibitors including
      • Mortality | GI side-effects | Renal disease
    • Thiazide or thiazide-like diuretics were more commonly associated with risk of hypokalaemia and hyponatremia
  • The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes

CONCLUSION:

  • The authors developed a new framework for doing observational health-care science at a large scale
  • This study is in keeping with current recommendations regarding overall similarity in effectiveness and safety between these various first-line medications
  • However
    • Thiazide or thiazide-like diuretics was associated with reduced risk with some adverse outcomes and had a superior risk profile compared to ACE inhibitors
    • Non-dihydropyridine calcium channel blockers were significantly inferior
  • Authors suggest that monotherapy initiation with a thiazide drug vs ACE inhibitor may be more effective with less complications

Learn More – Primary Sources:

Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis

Now You Can Get ObG Clinical Research Summaries Direct to Your Phone, with ObGFirst

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Related ObG Topics:

ACC/AHA Blood Pressure Guideline: Current Classification System and Treatment Targets
ACC/AHA Blood Pressure Treatment Guideline: Lifestyle Modification and Drug Therapy
Results of the TASMINH4 Study: Does Self-Monitoring Blood Pressure Lead to Better Hypertension Outcomes?
How Does Exercise Compare to Hypertension Drugs to Treat High Blood Pressure?

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