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

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?