Abstract

Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26 – 8.97; P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events.Trial RegistrationClinicaltrials.gov; NCT00133692

Highlights

  • Baseline office SBP, DBP, and heart rate (HR) were similar for these patients and were similar to the remaining 22,459 INternational VErapamil SR-Trandolapril STudy (INVEST) patients (Fig 2)

  • There was blunting of HR morning surge for atenolol vs. verapamil SR patients at 1 year (Fig 4; +2.8 vs. +4.5 beats/min/hr, respectively; P = 0.019). The results of this substudy of the INVEST indicate that, for patients with hypertension and coronary artery disease (CAD), both verapamil SR- and atenolol-based treatment strategies provide 24-hour blood pressure (BP) control with positive effects on important hemodynamic parameters that have been previously associated with adverse cardiovascular events

  • Atenolol provided a consistent decrease in nighttime HR, a relative increase in change from non-dipper to dipper status for both BP and HR, and a blunting of HR morning surge

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Summary

Trial Registration

Competing Interests: BASF Pharma and Abbott Laboratories had no role in the design or conduct of the study, collection or analysis of data, or preparation or approval of the manuscript. Dr Szirmai: Abbott Laboratories (consulting fees; travel support). Dr Keltai: Abbott Laboratories (travel support). Dr Messerli: Abbott Laboratories; Novartis; Daiichi Sankyo; Pfizer; Takeda; PharmApprove; Gilead; Servier; Bayer; Medtronic; Forest (remote); Boehringer Ingelheim (remote). Dr Bavry: Novartis Pharmaceuticals; American College of Cardiology/ CardioSource (contractor). Dr Handberg: NIH/NHLBI (grant support); Abbott; Fujisawa; Pfizer; GlaxoSmithKline (remote); US Patent #5,991,731 (royalties). Dr Mancia: SIRON BV (consulting fees); Boehringer Ingelheim; Novartis; Takeda (lecture fees). Bayer AG; Daiichi Sankyo; Menarini; Recordati; Servier (remote). Dr Pepine: Abbott Laboratories; Forest; Novartis/Cleveland Clinic; NicOx; Angioblast; Sanofi-Aventis; MedTelligence; Slack Inc., NIH/NHLBI (consulting fees); NIH/NHLBI, Abbott; NIH/NHLBI; Baxter; Pfizer; GlaxoSmithKline; Bioheart (grant). Drs Handberg and Pepine: payment for development of educational programs through the Vascular Biology Working Group (educational grants: AstraZeneca; Sanofi Aventis; Schering Plough; Daiichi Sankyo; Lilly; AtCor Medical; XOMA). Drs Denardo, Gong, Farsang, and Cooper-DeHoff: none declared. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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