Prevalence, predictors, and outcomes in treatment-resistant hypertension in patients with coronary disease

Am J Med. 2014 Jan;127(1):71-81.e1. doi: 10.1016/j.amjmed.2013.07.038. Epub 2013 Nov 7.

Abstract

Background: Increasingly, apparent treatment-resistant hypertension has been recognized. However, much of the prevalence, predictors, and outcomes are largely unknown, especially in patients with coronary artery disease.

Methods: We evaluated 10,001 patients with coronary artery disease who were enrolled in the Treating to New Targets trial. Apparent treatment-resistant hypertension was defined as blood pressure ≥ 140 mm Hg despite 3 antihypertensive agents or <140 mm Hg with ≥ 4 antihypertensive agents. The primary outcome was major cardiovascular events (composite of fatal coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke).

Results: Among the 10,001 patients in the trial, 1112 (11.1%) had apparent treatment-resistant hypertension. In a multivariable model adjusting for baseline differences, the treatment-resistant hypertension group had a 64% increase in primary outcome (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.39-1.94; P < .001), driven by a 69% increase in coronary heart disease death (HR, 1.69; 95% CI, 1.22, 2.34; P = .001) and 73% increase in nonfatal myocardial infarction (HR, 1.73; 95% CI, 1.39-2.16, P < .0001) when compared with the no apparent treatment-resistant hypertension group. In addition, patients with apparent treatment-resistant hypertension had a 71% increase in major coronary event (P < .0001), 45% increase in death (P = .001), 33% increase in heart failure (P = .05), 53% increase in any cardiovascular event (P < .0001), 60% increase in any coronary event (P < .0001), 68% increase in angina (P < .0001), and 51% increase in coronary revascularization (P < .0001) when compared with the no apparent treatment-resistant hypertension group. Results were largely similar whether the definition of apparent treatment-resistant hypertension was based on a blood pressure ≥ 140 mm Hg despite 3 agents or a blood pressure <140 mm Hg with ≥ 4 agents.

Conclusions: In patients with coronary artery disease, apparent treatment-resistant hypertension is associated with a marked increase in the risk of cardiovascular morbidity and mortality, including an increase in all-cause death.

Keywords: Outcome; Predictors; Prevalence; Resistant hypertension.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Atorvastatin
  • Blood Pressure / drug effects*
  • Calcium Channel Blockers / therapeutic use
  • Coronary Disease / complications*
  • Coronary Disease / mortality*
  • Diuretics / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Resistance
  • Female
  • Heptanoic Acids / therapeutic use
  • Humans
  • Hypertension / complications*
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Predictive Value of Tests
  • Prevalence
  • Pyrroles / therapeutic use
  • Risk Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Diuretics
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin